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Rintatolimod - AIM ImmunoTech

Drug Profile

Rintatolimod - AIM ImmunoTech

Alternative Names: AMP-516; AMP-518; Ampligen; Atvogen; Mismatched double-stranded RNA - AIM ImmunoTech; Poly I:Poly C12U; Poly I:polyC12U; poly(I) poly(C12,U); Rintamod; Vaccine-adjuvant-poly-I-polyC12U; Vaccine-adjuvant-rintatolimod

Latest Information Update: 28 Mar 2024

At a glance

  • Originator Hemispherx Biopharma
  • Developer AIM ImmunoTech; Centre for Human Drug Research; Erasmus MC; National Cancer Institute (USA); Roswell Park Cancer Institute; United States Army Medical Research Institute of Infectious Diseases; University of Pittsburgh
  • Class Adjuvants; Antineoplastics; Antiretrovirals; Antivirals; Oligonucleotides
  • Mechanism of Action HIV replication inhibitors; Immunostimulants; Interferon stimulants; Ribonuclease stimulants; RNA synthesis inhibitors; Toll-like receptor 3 agonists; VP35 protein inhibitors
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    Yes - Renal cell carcinoma; Pancreatic cancer; Ebola virus infections; Chronic fatigue syndrome; HIV infections; Malignant melanoma
  • New Molecular Entity Yes
  • Available For Licensing Yes

Highest Development Phases

  • Marketed Chronic fatigue syndrome; HIV infections; Malignant melanoma; Renal cell carcinoma
  • Phase II Colorectal cancer; Pancreatic cancer; Post acute COVID 19 syndrome; Prostate cancer; Triple negative breast cancer
  • Phase I/II COVID 2019 infections; Influenza virus infections; Ovarian cancer; Peritoneal cancer
  • Preclinical Ebola virus infections
  • No development reported Hepatitis B; Influenza A virus infections
  • Discontinued Smallpox; West Nile virus infections; Western equine encephalitis virus infections; Zika virus infection

Most Recent Events

  • 25 Mar 2024 Interim pharmacodynamics data from an expanded access program in Pancreatic cancer released by AIM ImmunoTech
  • 08 Feb 2024 Efficacy and adverse events data from a phase II trial in Post-acute-COVID-19-syndrome released by AIM ImmunoTech
  • 25 Jan 2024 Hemispherx Biopharma in collaboration with National Cancer Institute and Roswell Park Comprehensive Cancer Center reinitiates a phase II trial in Prostate cancer (Combination therapy, Late-stage disease, Neoadjuvant therapy) in USA (IV) in January 2024 (NCT03899987)

Development Overview

Introduction

Rintatolimod is a mismatched double-stranded RNA nucleic acid that induces interferon production and activates an intracellular enzyme (RNase-L) against viral RNA transcripts, being developed by AIM ImmunoTech (formerly Hemispherx Biopharma), for the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), pathogenic infections and cancer. The drug has been shown to activate toll-like receptor 3 (TLR-3), which is involved in the early detection of pathogens and the establishment of early defence mechanisms. Additionally, rintatolimod acts as a non-mitogenic stimulator of the immune system, as it works through cellular molecular cascades and therefore, is not vulnerable to mutational changes. Rintatolimod inhibits replication of the human immunodeficiency virus (HIV). In Canada, rintatolimod has been available since May 1996, under an emergency drug release statute, for the treatment of CFS and AIDS (acquired immunodeficiency deficiency syndrome). Rintatolimod is available for severe chronic fatigue syndrome on a named patient, cost-recovery basis in South Africa and launched for HIV infections, chronic fatigue syndrome, renal carcinoma and malignant melanoma in the US. Rintatolimod is available in Europe under an Early Access Programme. Intravenously administered rintatolimod is approved in Argentina as a therapy for chronic fatigue syndrome. Clinical development is underway for various indications in multiple countries. Preclinical development is underway for Ebola virus infections.

Clinical development for ovarian cancer, was underway in the US. However, the development has been suspended. Preclinical research for the treatment of western equine encephalitis virus infection and small pox was underway in the US. However, development of the drug for these indications seems to be discontinued. Phase III development in chronic fatigue syndrome was conducted and awaiting regulatory approval in the European Union. As of September 2006, no further drug development was reported in these indications. Phase II development in HIV infections was conducted in the US, but the drug development was suspended in March 2007. Preclinical development of Rintatolimod was underway for West Nile virus infections, Zika-virus-infection in US and Italy. However, as at July 2020, these indications were not listed on the pipeline and development seems to be discontinued.

An intranasal formulation of rintatolimod is being referred by AIM ImmunoTech to be used as an influenza vaccine enhancer.

Hemispherx reported that it is exploring co-development partnerships with vaccine producers [1] .

As of October 2023, rintatolimod is available for licensing worldwide [2] [3] .

In August 2019, Hemispherx Biopharma changed its name to AIM ImmunoTech [4] .

Company Agreements

In January 2023, AIM ImmunoTech entered into an external sponsored collaborative clinical research agreement with Erasmus MC and AstraZeneca. Under the agreement, Erasmus MC is planning to perform an investigator-initiated DURIPANC Study, entitled “Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy effect. Both study drugs will be provided by AstraZeneca and AIM ImmunoTech. [5]

In March 2022, AIM ImmunoTech announced that it has officially withdrawn its application from the Medicines and Healthcare Regulatory Agency and terminated its agreement with hVIVO and incurred a cancelation fee of $US60,000 which was paid in the first quarter 2022. Previously, in September 2021, AIM ImmunoTech and hVIVO signed a clinical trial agreement (CTA) for the phase IIa trial. In July 2021, AIM ImmunoTech entered into a clinical trial collaboration with hVIVO to test rintatolimod (Ampligen) in a phase IIa study as a potential intranasal antiviral therapy using a human rhinovirus hRV (common cold virus) and influenza A virus (H3N2). AIM ImmunoTech has signed a contract to sponsor the Human Challenge Trial (HCT) while, the antiviral study will be conducted by hVIVO.

In April 2021, AIM ImmunoTech entered into a material transfer and research agreement (MTA) with the University of Cagliari. The MTA relates to the research and development of the effects of ampligen and its ability to induce interferon production in several cell lines, and also on the ability of the Ebola virus protein VP35 to bind to viral dsRNA and impede interferon’s upregulation and activity, and on Ampligen’s ability to reverse VP35 inhibition of interferon production in biological systems. The research is active and ongoing. [9]

In January 2021, AIM ImmunoTech entered in a clinical trial agreement with Centre for Human Drug Research for the AMP-COV-100 (CHDR2049) clinical study of ampligen in COVID-2019 infections. [10]

In July 2020, AIM ImmunoTech has entered into a clinical trial agreement (CTA) with Roswell Park Cancer institute to support Roswell Park's phase I/IIa trial of Ampligen (rintatolimod) in combination with interferon alfa-2b, in cancer patients with COVID-19, the disease caused by the SARS-CoV-2 coronavirus. Funding for the clinical trial is provided, in part, through grants from the National Cancer Institute and AIM, as well as institutional support from Roswell Park. [11]

In July 2020, AIM ImmunoTech signed a material transfer and research agreement with Japan's National Institute of Infectious Diseases (NIID) and Shionogi to test AIM's drug Ampligen as a potential adjuvant therapy for COVID-19. Under the agreement, AIM will provide Ampligen samples for various research projects. The details of all preclinical and clinical results will remain confidential until released by NIID and Shionogi. [12]

In January 2017, Hemispherx (now AIM ImmunoTech) extended its rintatolimod European Early Access Program (EAP) agreement with myTomorrows to enable access of Ampligen® to chronic fatigue syndrome/myalgic encephalomyelitis patients as well as pancreatic cancer patients beginning in the Netherlands. Hemispherx, in April 2018, amended its agreement to include management of a Special Access Programme (SAP) in Canada for patients suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). In June 2018, the company announced that the EAP approval was accepted in Netherlands for pancreatic cancer. myTomorrows is Hemispherx’s exclusive service provider in Europe and Turkey and will manage all EAP activities relating to the pancreatic cancer extension of the programme. In May 2016, Hemispherx executed an amended and restated agreement signed earlier in August 2015 with myTomorrows, for the commencement and management of an EAP for rintatolimod in all of Europe and Turkey. Under the collaboration, myTomorrows will conduct EAP activities to include the supply of the drug for the treatment of chronic fatigue syndrome as well as collaborate with the physicians to capture data that may support the regulatory approval worldwide. [13] [14] [15] [16] [17] [18] [4]

In March 2018, University of Nebraska Medical Center (UNMC) and Hemispherx Biopharma (now AIM ImmunoTech) entered into an agreement to test the capability of rintatolimod to enhance immune responses. The study will test the capability of rintatolimod when combined with peptide vaccine developed by UNMC for pancreatic cancer. UNMC researchers will immunise mice with pancreatic tumours expressing MUC1. [19] [4]

In June 2016, Hemispherx Biopharma obtained a comprehensive omnibus assignment of intellectual property created by William Carter, the former CEO of Hemispherx, resulting in obtaining complete and irrevocable ownership of intellectual property related to Ampligen® [20] .

Hemispherx Biopharma entered into an exclusive license agreement with Emerge Health for the commercialisation of of rintatolimod for the treatment of chronic fatigue syndrome in Australia and New Zealand. Emerge and Hemispherx will collaborate on seeking approval of the product from Australia's Therapeutic Goods Administration (TGA) and New Zealand's Medicines and Medical Devices Safety Authority (Medsafe) and Emerge will distribute the product in both the countries on a named-patient basis. Emerge will also seek orphan drug designation and Hemispherx will provide support for this. Hemispherx will supply rintatolimod at a predetermined transfer price [21] .

In September 2014, Hemispherx entered into a collaborative agreement with the Swiss Department of Defense, Civil Protection and Sports to evaluate rintatolimod against Ebola virus infections, as part of the DEA (Data Exchange Agreement) Annex for Medical Preparedness and Bio-Defense Agreement between the Swiss Surgeon General and the US Department of Defense [22] . In the same month, Hemispherx entered into five integrated research collaborations to develop therapeutic cocktails against Ebola. These collaborations are with the National Institutes of Allergy and Infectious Diseases, the United States Army Medical Research Institute in Infectious Disease, the Swiss Department of Defense, Howard University and a US-based facility with biosafety level 4. Rintatolimod has shown potential value with respect to inclusion in several therapeutic cocktails under development for Ebola [23] .

In July 2014, Hemispherx Biopharma entered into a strategic alliance with Bioclones, under which the companies agreed to jointly pursue regulatory approval of rintatolimod in South Africa [24] .

Hemispherx entered into an exclusive revenue sharing sales, marketing, distribution and supply agreement for rintatolimod in Argentina with GP Pharm Latino-America, an affiliate of Spanish GP Pharm SA, in June 2010. This agreement expired in June 2015 and was renewed in May 2016 with the same clauses as earlier. Under the terms of the agreement, GP Pharm will be responsible for gaining regulatory approval and for commercialisation of rintatolimod for the treatment of CFS in Argentina. GP Pharm also has been granted expanded rights to sell the therapeutic into other Latin American countries, based upon GP Pharm achieving certain performance milestones. In December 2010, the agreement was amended to immediately include Mexico in the agreed territories and GP Pharm Mexico will be responsible for gaining regulatory approval for rintatolimod for the treatment of CFS in Mexico. Hemispherx will manufacture and supply rintatolimod to GP Pharm [25] [26] [27] .

Hemispherx Biopharma and the Lovelace Respiratory Research Institute (LRRI) entered into a research contract worth more than $US1 million in November 2008 to conduct additional preclinical studies with rintatolimod to enhance the NDA filing status of the product. Projected preclinical studies under the contract are designed to enhance the cellular understanding of the product's molecular actions across various animal species, including humans and should facilitate the filing of additional NDAs for potential treatment of CFS in various countries outside North America [28] .

In December 2007, Hemispherx Biopharma notified Esteve of its intention to terminate the licence agreement between the two companies, as certain contractually required clinical trials had not been performed by Esteve. Esteve has applied for arbitration but Hemispherx intends to counterclaim [29] . In March 2002, Esteve and Hemispherx entered into a collaborative agreement under which Esteve will be the sole distributor of rintatolimod in Spain, Portugal and Andorra for the treatment of CFS. Under this agreement, in addition to other terms, Esteve will also collaborate in the drug product development by conducting clinical studies in Spain in patients co-infected with HIV/HCV. Pertaining to the infection time, the treatment would be split into two sets. the first set would consist of patients co-infected <12 months and the second would include those who have had consistent, chronic HIV-HCV co-infection for >12 months.

Inactive agreements

Hemispherx Biopharma's agreement with BIKEN in Japan expired in September 2010. The two parties were working together to develop a nasally administered influenza vaccine utilising research done by Hemispherx and the Japanese National Institute of Infectious Diseases (NIID). Hemispherx successfully completed its 3-year research programme with the NIID during the second quarter of 2010 [30] [31] .

In February 2004, Fujisawa Deutschland GmbH, a subsidiary of Fujisawa Pharmaceutical Co., entered into an option agreement with Hemispherx Biopharma with the intent of becoming a distributor for rintatolimod for the potential treatment of CFS in Germany, Switzerland and Austria. A fee of €400 000 was paid pursuant to the terms of the option agreement, and upon execution of the Distribution Agreement, Fujisawa was to pay Hemispherx fees and milestone payments with a potential worth of several millions of dollars [32] . However, this agreement has been terminated.

In September 2003, Hemispherx Biopharma entered into an agreement with Guangdong Medicine Group Corporation to organise clinical trials, marketing, sales and distribution for both of its lead compounds, rintatolimod and Alferon N® in the People's Republic of China [see RDI Profile 800006022]. The agreement stipulated that the Guangdong Medicine Group Corporation (GMC) will conduct clinical trials with rintatolimod, for the treatment of HIV. All costs related to the trials were to be covered by GMC. Additionally, GMC had to develop and implement marketing and promotional programmes [33] . It appears that this agreement is no longer active.

In May 2003, Hemispherx Biopharma and the Center for Cell and Gene Therapy entered into a research project agreement that would see rintatolimod implemented in a protocol used in patients with relapsed EBV-positive Hodgkin's lymphoma [34] . This collaboration no longer appears to be active.

Crystaal Corporation (later Biovail Pharmaceuticals Canada) acquired exclusive marketing rights to rintatolimod in Canada in February 2000. However, this agreement no longer appears to be active.

In an arrangement between Hemispherx and Bioclones, Bioclones had certain marketing rights for rintatolimod in the Southern Hemisphere, UK and Ireland. However, the agreement between Hemispherx and Bioclones has ended.

Manufacturing

Hemispherx signed a letter of intent with HollisterStier Laboratories for the contract manufacturing of rintatolimod in October 2005. This agreement will enable Hemispherx to manufacture the active pharmaceutical ingredient for 10 000 doses of rintatolimod per week if initial objectives are achieved, in combination with a polymer production facility which is under construction [35] .

Key Development Milestones

As of June 2021, rintatoimod, was launched in the US for the treatment of severe chronic fatigue syndrome. In December 2017, Hemispherx announced that discussions are ongoing with the US FDA on the next steps regarding a New Drug Application (NDA) for rintatolimod (Ampligen®) in ME/CFS [36] . The US FDA issued a Complete Response Letter (CRL) for Hemispherx Biopharma's NDA for rintatolimod (Ampligen®) in February 2013. In its CRL, the agency declined to approve rintatolimod for the treatment of CFS. The FDA said that the company should conduct at least one additional clinical trial, complete various non-clinical trials and conduct selected data analyses. The agency has also stated that there is no sufficient information on the efficacy and safety of rintatolimod in CFS due to a limited safety database and a number of discrepancies within the data provided [37] . In March 2016, the company announced that it had completed discussions with NIH's National Institute of Neurological Disorders and Stroke to discuss how the NIH’s research may assist the company in closing key questions from the FDA [38] . Hemispherx Biopharma reported in its 2014 annual report that it plans to conduct an end-of-review meeting with the FDA to clarify and narrow the outstanding issues regarding the further development of Ampligen® for the treatment of CFS.

In June 2019, AIM Immunotech reported that the company received import clearance from Argentina's Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica (ANMAT), for rintatoimod, for the treatment of severe chronic fatigue syndrome. This is followed by export clearance issued by the US FDA in September 2019, under the section 802 (b) (2) of the U.S. Federal Food, Drug and Cosmetic Act. ANMAT will conduct a final inspection of the product and release tests before granting final approval to begin commercial sales. Once final approval by ANMAT is obtained, GP Pharma will begin distributing the in Argentina. ANMAT approved rintatolimod for the treatment of patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in Argentina in August 2016. The approval was based on clinical data from two pivotal trials, AMP-516 and AMP-502. In July 2012, Hemispherx Biopharma had submitted the NDA to ANMAT, through its local representative GP Pharm in Argentina, seeking approval of rintatolimod for the treatment of CFS under orphan drug status. The approval is expected to have a beneficial effect on AIM ImmunoTech's early access program partnerships in Europe and Australia [39] [25] [40] [41] [42] .

In August 2012, Hemispherx Biopharma filed with the US FDA, its complete response to the agency's 2009 CRL to the NDA for rintatolimod for CFS. The FDA accepted the filing as a complete class 2 response and the PDUFA date was set in February 2013 [43] [44] [45] . In November 2010, Hemispherx Biopharma filed a request with the US FDA to maintain an active NDA for rintatolimod to treat CFS [46] [47] [48] . New analyses from the AMP 516 study published in a PLoS ONE report in March 2012, supplement the original study findings and helped support a re-filing of the NDA [49] [50] . In December 2012, the FDA Advisory Committee made recommendations for an additional controlled clinical trial of rintatolimod prior to approval, as the company had not provided sufficient evidence of efficacy and safety [51] .

The FDA accepted Hemispherx's NDA filing (originally submitted in October 2007) for review in July 2008 [52] . Hemispherx received the CRL in December 2009, stating that the two primary clinical studies submitted did not provide credible evidence of efficacy of rintatolimod and recommended at least one additional study of sufficient size and sufficient duration (6 months) [53] . As part of the NDA submission, the company had requested that complete rodent carcinogenicity studies in two species be waived, but the waiver was not granted. Certain additional non-clinical studies and additional data to support non-clinical studies already submitted were also recommended. Prior to the receipt of the CRL, Hemispherx had already begun many of the additional studies and collection of the requested additional data. Hemispherx submitted preclinical data in January 2010 that showed no evidence of antibodies to rintatolimod, and no increase in certain cytokines, after administration of the drug in primates at doses used in clinical studies. The company believed that the data were sufficient to address certain preclinical issues mentioned in the CRL [54] . In the CRL, the FDA also commented on rintatolimod manufacturing, noting the need to resolve outstanding inspection issues at the facilities producing the drug. Hemispherx submitted new data regarding this matter in December 2009 and believes that all manufacturing concerns have been addressed [55] .

In June 2018, Hemispherx Biopharma completed production of a commercial size batch of more than 8 500 vials of Ampligen®. AIM ImmunoTech intends to generate substantial revenues from this batch through an existing 2 100 vial stock order from myTomorrows for its early access programmes in ME/CFS and pancreatic cancer in Europe and Canada. This vial stock will be utilised to meet projected needs for clinical trials of Ampligen in the US, including the FDA-approved expanded access compassionate care program in ME/CFS, and clinical trials involving various cancers with Ampligen® as a stand-alone therapy as well as in combination with checkpoint blockade technology. Hemispherx Biopharma also reported that it filled and finished production of another batch of 8 000 vials which will supply the initial demand for the anticipated commercial launch of Ampligen in Argentina, for treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [56] [57] .

In August 2017, Hemispherx Biopharma, in collaboration with Millions Missing Canada, plans advance CFS/ME research and potential treatments in Canada. AIM ImmunoTech and Millions Missing Canada will follow the model that Hemispherx used to obtain approval for rintatolimod in Argentina by seeking a Canadian Pharmaceutical partner to file for regulatory approval in Canada. The existing rintatolimod new drug application database will be used to gain approval of the product [58] .

In March 2017, Hemispherx re-initiated its US-based cost recovery programme at the price increase recently approved by the FDA [59] .

In December 2017, Hemispherx Biopharma reported that its Contract Manufacturing Organization for rintatolimod (Ampligen®) completed a commercial scale demonstration or engineering manufacturing run, along with the re-qualifications of analytical methods that were agreed upon during a previous successful Pre-Approval Inspection as necessary prior to the production of commercial lots of rintatolimod [36] .

In October 2016, Hemispherx Biopharma reported that the transfer of technology to Avrio Biopharmaceuticals related to contract manufacturing of rintatolimod for use in the Expanded Access Programme in Turkey and England has been completed. The first cGMP lot is expected to be compounded, filled and finished in November and released in December 2016 [60] .

In August 2015, Hemispherx Biopharma plan to file for regulatory approval for rintatolimod worldwide, including Europe, Latin America, Australia, New Zealand and the US [13] . The company also plans to introduce the product in Turkey under an Expanded Access Programme (EAP).

In March 2014, Hemispherx reported that following the notification of clearance of the Rintamod™ trademark in Chile, Peru and Uruguay, Hemispherx and GP Pharma are preparing to file rintatolimod for approval in these countries for the treatment of CFS [61] .

AIM ImmunoTech plans to initiate a confirmatory phase II trial for rintatolimod in CFS/ME in the US [62] .

In March 1997, Hemispherx Biopharma initiated a AMP-511 expanded access programme (EAP) phase III open-label trial to evaluate the safety of rintatolimod in 100 patients with severely debilitating chronic fatigue syndrome in the US (AMP 511; NCT00215813). In November 2010, Hemispherx expanded the enrolment of this trial in conjunction with ongoing analysis of the completed phase III AMP 516 study. The company is conducting analysis into the possible viral aetiology of CFS [63] [48] . In September 2015, Hemispherx reported the approval of patient assistance programme for the AMP 511 study, thereby allowing the patients in the study to receive the drug through March 2016, at a cost-recovery rate, since they entered the study [64] . As at December 2016, 27 patients accessed rintatolimod, under the patient assistance AMP 511 study, authorised by the US FDA in May 1997 [65] . In June 2018, Hemispherx Biopharma expanded its APM 511 programme in the US and expanded patient enrolment [66] . The US FDA has approved the reimbursement rate of $200 per vial for the direct costs of the drug through EAP [67] . In January 2019, Hemispherx reported that the US FDA authorised the AMP 511 protocol to expand compassionate care where there is no commercially approved therapy. New recruits will not be eligible to participate in a future confirmatory trial. Additionally, a plan for a future pivotal confirmatory trial is underway, wherein previously-treated patients will not be eligible for participation [68] . As of September 2021, 14 patients were enrolled in this EAP trial, including three post-COVID-2019 patients with cognitive dysfunction, in the same month. The company received IRB approval for a public notification of potential enrollment in the post-COVID-19 long hauler portion of the active AMP-511 EAP protocol. Patients in the trial will be treated with Ampligen. AIM is currently preparing the IRB-approved protocol for submission to the US FDA. The Ampligen EAP protocol is authorized to enroll up to 100 active trial participants, 20 of whom may be long haulers [69] [70] [71] [72] . In 2021 AIM ImmunoTech dosed its first long hauler patient with rinatolimod in its post-COVID-19 long hauler portion of the active AMP-511 EAP in the United States [73] . In May 2022, the company released positive data of post-COVID patients with new onset ME/CFS following acute COVID-19 [74]

In May 2004, Hemispherx reported favourable efficacy and safety data from its 40-week, randomised, parallel, placebo-controlled, double-blind, phase III study of rintatolimod in 234 patients with severely debilitating CFS, which was initiated in December 1998 (AMP 516; NCT00215800) [75] [76] . The trial was completed in February 2004. Results of the US-based study were published in the Journal of Applied Research and PLoS ONE [49] . In September 2015 and October 2016, a retrospective analysis of data from the trial was released [62] [77] .

In February 2000, Crystal Corporation (now Biovail Pharmaceuticals Canada) acquired exclusive marketing rights to rintatolimod in Canada. Rintatolimod has been available in Canada since May 1996 under the Canadian Emergency Drug Release Programme for the treatment of CFS and immune dysfunction syndrome from Rivex Pharma (Helix BioPharma).

Rintatolimod has been granted orphan drug status for the treatment of CFS in the US and Europe. Hemispherx had previously applied for approval to use rintatolimod for CFS in Europe [78] . The US FDA also granted orphan drug designation to rintatolimod for the treatment of HIV/AIDS, renal cell carcinoma and malignant melanoma.

In April 2023, AIM ImmunoTech announced central Institutional Review Board (IRB) approval for the protocol of its phase II trial AMP 518, evaluating Ampligen® as a therapeutic for patients with post-COVID conditions in the US [79]

In August 2022, AIM Immunotech in collaboration with Roswell Park Cancer Institute initiated a phase-II trial to evaluate the efficacy of type-1 polarized dendritic cell (aDC1) vaccine in combination with tumor-selective chemokine modulation (“CKM”) comprised of Interferon alpha 2b, rintatolimod and celecoxib in patients with refractory melanoma(NCT04093323; I 82419). The open-label trial intends to enrol approximately 24 patients in the US [80] . In August 2022, Company initiated patient enrollment in the trial [81] .

Rintatolimod has been evaluated in phase II trials for the treatment of CFS/ME [82] [83] .

Bioclones planned to initiate clinical studies with rintatolimod for the treatment of CFS in Australia; however, no recent development has been reported.

In August 2018, Hemispherx reported that rintatolimod synergistically potentiated anti-tumour activity and median survival of other anti-cancer compounds including checkpoint inhibitors in preclinical studies [84] . In January 2018, Hemispherx released data from preclinical studies and preliminary clinical data on a favourable immune-modulatory activity of rintatolimod on the tumour micro environment, which potentially could help convert cold tumours to tumours that will respond to immunotherapeutic drugs such as checkpoint inhibitors. In addition, rintatolimod in combination with alpha interferon and COX-2 inhibitors uniformly induced attraction of killer T cells into the tumor lesions of multiple human cancer types, rather than healthy tissue, and simultaneously eliminated undesirable Treg cells and local production of other suppressive factors such as interleukin-10 [85] [86] .

Hemispherx Biopharma, in September 2015, reported positive outcome from preclinical studies to evaluate the in vitro exposure of peripheral blood mononuclear cells (PBMCs) from 15 CFS patients [87] .

In January 2015, Hemispherx reported that rintatolimod 400mg bid, in natural killer cells donated by patients with chronic fatigue syndrome, increased the in vitro mean natural killer cell activity [88] .

A preclinical study conducted by Utah State University in collaboration with Yale University, Vanderbilt University, and the Centre d'Immunologie de Marseille-Luminy demonstrated the roll of toll-like receptor 3 (TLR-3) in rintatolimod's mechanism of action. This study, evaluating the mechanism of action in TLR-3 knockout mice, was conducted under a NIH contract [89] .

Viral infections

In September 2013, Hemispherx reported that it intends to undertake major programmes to investigate rintatolimod as a biodefence agent, with a focus on the prevention or treatment of H7N9 pandemic influenza virus infections, alpha virus infections including Venezuelan Equine Encephalomyelitis (VEE), and Middle East Respiratory Syndrome (MERS). The in vitro and in vivo studies have confirmed that rintatolimod is highly active against these virus classes [90] .

COVID-2019 infections and other respiratory viral diseases

In November 2023, AIM ImmunoTech completed a phase II trial that assessed the efficacy and safety of Ampligen® administered twice weekly by intravenous (IV) infusions in participants experiencing the post-COVID condition (NCT05592418; AMP-518). The randomised trial was initiated in June 2023 and enrolled 80 participants in the US [91] . earlier, in October 2022 , AIM ImmunoTech submitted an investigational new drug application to U.S. Food and Drug Administration (FDA ) for rintatolimod to initiate a phase II study for patients with post-COVID conditions [92] . In July 2023, AIM ImmunoTech enrolled and dosed the first participant in the trial [93] . In August 2023, the company has completed planned enrolment of 80 participants in the study and expects to complete dosing of the last study patient in Q4 2023 [94] . In November 2023, AIM ImmunoTech announced that the last subject has completed treatment in the phase II trial of rintatolimod. The company also reported that no severe adverse events observed [95] . In February 2024, the company released preliminary results from the trial [96] .

In September 2021, AIM ImmunoTech had submitted a pre-investigational new drug (Pre-IND) application to the US FDA for two separate phase II clinical studies of rintatolimod as both an infusion and an intranasal therapy for COVID-2019 infections. The two clinical trials will be phase II, randomised, double-blind, placebo-controlled studies to evaluate the efficacy and safety of rintatolimod as an intravenous therapy or placebo and an intranasal therapy. The phase II protocols include exploratory endpoints that the company believes could support its recently filed provisional patent application [97] .

In March 2022, AIM ImmunoTech officially withdrew its application from the Medicines and Healthcare Regulatory Agency (MHRA) for a phase IIa trial and terminated its agreement with hVIVO [8] . Previously, in July 2021, AIM ImmunoTech had planned to initiate a phase IIa Human Challenge Trial (HCT) to test rintatolimod (Ampligen) as a potential intranasal antiviral prophylactic therapy using a human Rhinovirus hRV (common cold virus) and Influenza infections. The company had signed a contract with hVIVO, a subsidiary of Open Orphan plc to sponsor the study [6] [98] [99] . In September 2021, the company submitted its study protocol to the Oxford Research Ethics Committee (REC)/Medicines and Healthcare Regulatory Agency (MHRA). The REC had approved the protocol, but the MHRA provided a response outlining areas of the submission where it required additional information. The company had intended to resubmit its proposed protocol [72] .

In September 2021, AIM ImmunoTech submitted a Pre-Investigational New Drug application (Pre-IND) to the US FDA for a phase II study of rintatolimod (Ampligen) as a potential infusion therapy for post-COVID-19 cognitive dysfunction (PCCD). The phase II trial will be a two-arm, randomised, double blind, placebo controlled study to evaluate the efficacy and safety of rintatolimod in patients experiencing PCCD. About 80 patients will be randomised 1:1 to receive twice weekly infusions of rintatolimod or placebo for a period of 12 weeks. In September 2021, AIM ImmunoTech announced that the meeting request has been deemed sufficient for transfer to the US FDA’s Division of Neurology by the US FDA's Covid Scientific Technical Triage Team [100] . In December 2020, IRB granted approval to include patients previously diagnosed with SARS-CoV-2 and now demonstrated post-acute infection chronic fatigue-like symptoms to be included in the expanded access programme [101] .

In March 2023, Roswell Park Cancer Institute, in collaboration with AIM ImmunoTech and National Cancer Institute suspended a phase I/IIa trial in order to revise the trial protocol. The trial was initiated in September 2020, to evaluate the side effects of rintatolimod, in combination with interferon (IFN) alpha-2b, in cancer patients with mild or moderate COVID-19 infection (I659920; NCI2020-02317; P30CA016056; NCT04379518). The open-label, randomised trial intends to enrol approximately 64 patients in the US [102] [103] . In May 2020, the US FDA approved the first human trial to evaluate the safety and effectiveness rintatolimod, in combination with interferon alfa-2b, in cancer patients with COVID-2019 infections [104] . In November 2020, first patient was dosed in this study. In March 2021, AIM ImmunoTech announced that the Institutional Review Board of Roswell Park Comprehensive Cancer Center approved a protocol ammendment for the trial for randomisation of additional twenty patients. Ten patients will receive a single dose of rintatolimod, but no interferon treatment, and the other ten will receive best available care only [105] [106] . Funding for the clinical trial was provided, partly through grants from the National Cancer Institute and AIM, as well as institutional support from Roswell Park [107] .

In March 2021, AIM ImmunoTech in collaboration with Centre for Human Drug Research (CHDR) initiated the phase I AMP-COV-100 trial to assess the safety, tolerability and biological activity of repeated intranasal administration of rintatolimod as a prophylaxis or treatment for COVID-19 infections and other respiratory viral diseases (CHDR2049; AMP-COV-100). The prospective, double-blind trial completed enrolment of 40 healthy volunteers in Netherlands. The trial randomised volunteers into four cohorts; cohort one, two, three and four will receive 75 μg, 200 μg, 500 μg and 1250 μg of rintatolimod, respectively, compared with placebo [108] [98] . In February 2021, AIM ImmunoTech received approval from the required Ethics Committee in the Netherlands to commence the phase I trial [109] [110] . In April 2021, AIM ImmunoTech announced positive safety data from the cohort one, allowing for the dose escalation in the cohort two of the trial [111] . In April 2021, AIM ImmunoTech announced completion of dosing and positive safety data from the second cohort, allowing for the dose escalation in the third cohort of the trial [112] . In May 2021, AIM ImmunoTech completed dosing of Cohort three in the phase I trial reporting no serious adverse events [113] . In October 2021, AIM ImmunoTech reported that the phase I part of the trial was completed where rintatolimod was generally safe and well tolerated with no severe adverse events were reported [114] . In December 2022, AIM ImmunoTech released data from the trial [115] .

In August 2020, AIM Immuno Tech reported that it identified an in vitro model in which rintatolimod at intranasal dosage levels resulted in decrease in SARS-CoV-2 infectious viral yields by 90%. The data supported the development of rintatolimod as both prophylaxis and early onset intranasal therapy of COVID-2019 infections [116] . In March 2020, AIM Immuno Tech announced intention to conduct clinical trials with intranasal and oral formulation of rintatolimod (Ampligen®) for a protective prophylactic as well as intravenous formulation for early-onset therapy of COVID-2019 infection in Argentina, the Asia, the Europe and the US. The company is also in discussions with myTomorrows and the Erasmus Medical Center in the Netherlands Rotterdam, to explore expedited pre-clinical and clinical trials of Ampligen® for a protective prophylactic as well as early-onset therapy of COVID-2019 infections [117] .

In March 2020 AIM Immuno Tech announced that rintatolimod (Ampligen) will be tested for the potential treatment of COVID-19 by National Institute of Infectious Diseases (NIID) in Japan [118] .

In February 2020, AIM Immuno Tech announced that the company intends to introduce rintatolimod (Ampligen) in China for the treatment of COVID-19 virus infection [119] .

In February 2020, AIM Immuno Tech released preclinical pharmacodynamics data for severe acute respiratory syndrome caused due to COVID-2019 infections [120] . In May 2021, AIM Immuno Tech released preclinical data from animal and in in vitro models [121] .

Hemispherx Biopharma reported in February 2010 that it was holding discussions with clinical research organisations in China with a view to starting clinical antiviral programmes for rintatolimod in that country. The clinical programmes will relate to use of the drug to treat SARS. The company stated that this decision was based on promising results for the drug in an animal model of SARS; the preclinical work was conducted by independent researchers at Utah State University and the University of North Carolina [122] .

In June 2021, AIM Immuno Tech released preclinical data which includes rintatolimod in the treatment of COVID-2019 infections in pancreatic cells [123] [124]

In May 2003, Hemispherx initiated a collaboration with the Genome Institute of Singapore (GIS), to evaluate rintatolimod and Alferon® N for the treatment of SARS [see RDI Profile 800006022] [125] . Hemispherx entered into a Research Project Agreement with the Institute for Medical Virology, Johann Wolfgang Goethe University Hospital, Germany, to evaluate the antiviral activity of rintatolimod and Alferon® N, alone and in combination against the SARS coronavirus.

NIH-sponsored studies of potential therapies for SARS identified rintatolimod as having unusually high and consistent antiviral activity against human coronavirus, the pathogen implicated as the causative agent of the disease. Rintatolimod demonstrated very high potency at very low concentrations (0.4 µg/mL) and had a favourable safety profile [126] . In October 2003, Hemispherx announced that, based on these promising new results, the company would stockpile injectable and/or oral formats of rintatolimod and Alferon® [127] .

Ebola virus infections

In March 2023, AIM ImmunoTech announced its intention to file Investigational New Drug (IND) applications to study the use of rintatolimod as an early onset therapy for the treatment of ebola virus disease, and for the prevention of ebola virus reactivation [128] .

In November 2022, US FDA granted orphan drug designation to rintatolimod for the treatment of ebola virus disease [129] .

In May 2015, rintatolimod received orphan drug designation by the EMA for the treatment of Ebola virus disease. Hemispherx Biopharma reported in March 2015 that rintatolimod had received a positive opinion from the Committee for Orphan Medicinal Products (COMP) regarding its orphan drug application in the EU [130] . The application was supported by the in vitro and in vivo data in appropriate preclinical models relevant to the EVD indication conducted in Italy, as well as, clinical safety data obtained from non-EVD clinical studies. The data suggested that rintatolimod successfully competed with dsRNA for Ebola VP35 binding with a low concentration reflected by an IC50 = 1.1 µg/ml [131] . Results from the preclinical mouse model of Ebola virus were released in February 2015 [132] [133] . Additionally, Hemispherx announced that it is developing a protocol for the clinical trial of the drug in Ebola virus infection [134] . In November 2014, Hemispherx Biopharma and United States Army Medical Research Institute of Infectious Disease (USAMRIID) reported that low concentrations of rintatolimod demonstrated effective protection of human cells against Ebola virus in in vitro studies. Furthermore, USAMRIID reported its plans to continue to collect data and to initiate in vitro synergy studies using rintalimod and interferon alpha n3 [see RDI Profile 800006022]. These studies are being planned to establish a basis for clinical interventions in both preventative and therapeutic settings of Ebola virus disease [135] [136] . Rintatolimad was shown to inhibit the Ebola meningenome by investigators at the Howard University [137] . Biochemical in vitro data was reported later in the same month, by the University of Cagliari, Italy [138] . In September 2014, Hemispherx collaborated with researchers from the USAMRIID to assess rintalimod and interferon alpha n3 as a potential prevention or treatment for Ebola virus infections [139] .

In March 2023, AIM ImmunoTech released pharmacodynamics data from the preclinical studies [140]

HIV and HCV infections

As of June 2021, rintatolimod for the treatment of HIV infections was launched in the US.

A phase IIb study of rintatolimod in HIV was completed in the US (NCT00035581) [141] . This trial evaluated the potential effectiveness of rintatolimod to increase the highly active anti-retroviral therapy (HAART)-free time interval before HIV rebound during the strategic therapeutic intervention (STI) of HAART. A phase II study assessing the safety and efficacy of adding rintatolimod to a STI of HAART was also completed in the US (NCT00035893) [142] . Hemispherx also conducted phase II trials in patients with chronic hepatitis B. However, Hemispherx has stated that these studies were not well-controlled, therefore further testing will be necessary. The company's main priority is to the development of rintatolimod in CFS, and it is assumed that trials in other indications will resume when approval has been achieved in CFS.

In July 2004, Esteve Laboratorios in Spain received authorisation from the Spanish Ministry of Health to import rintatolimod for a clinical trial in HIV/HCV coinfected patients. Hemispherx shipped the required number of vials of rintatolimod for the trial [143] . A phase II pilot study was initiated by Hemispherx and Esteve in January 2005 to evaluate the antiretroviral effect of rintatolimod in the treatment of patients infected by HIV-1, with or without HCV co-infection [144] [145] . However, Esteve discontinued this trial due to poor patient recruitment and no further development has been reported.

Influenza virus infections

In September 2021, AIM announced that the proposed protocol for the phase IIa Human Challenge Trial (HCT) study had been submitted to the Oxford Research Ethics Committee/Medicines and Healthcare Regulatory Agency and its response is expected by mid November. Preparations to commence the study are now underway, pending the expected approval. This antiviral study will be conducted by hVIVO, a subsidiary of Open Orphan, to test Ampligen as a potential intranasal prophylactic using a human rhinovirus (HRV-16, a common cold virus) and influenza A virus (H3N2). The HCT will allow AIM to expedite the development process for Ampligen by ensuring full exposure of both the control group and the Ampligen group, so as to assess whether there is a prophylactic effect [7] .

In August 2017, Hemispherx Biopharma and University of Alabama announced the initiation of full data analysis of the phase I/II trial to assess immunogenicity and safety of FluMist® [see AdisInsight drug profile800004972] with and without rintatolimod (AMP-600; NCT01591473). The full data analysis was commenced following the FDA's evaluation, as communicated in August 2017, of preliminary reports of blinded-study finding. Previously, in February 2017, Hemispherx Biopharma terminated the trial stating that CDC indicated nasal spray flu vaccine should not be used during 2016-2017. The two-staged, randomised, double-blind trial was initiated in April 2012, and enrolled 12 volunteers in the US. The trial assessed the immunogenicity and safety of intranasal FluMist [see AdisInsight RDI profile800004972] administered sequentially with intranasal rintatolimod. The intranasal administration of rintatolimod was well tolerated in healthy volunteers. Immunogenicty data from the trial were released in January 2018. In July 2018, Hemispherx filed positive safety report on this trial [146] [147] [148] [149] [150] .

Hemispherx Biopharma was planning to conduct a placebo-controlled phase II study to investigate the efficacy of adding rintatolimod to standard care in seriously ill patients with influenza virus infections. The company has entered into an agreement with Fountain Medical Development (a Clinical Research Organisation) to prepare, file and gain approval to conduct the trial in China. However, status of this trial is unknown [151] [152] .

Pre-clinical studies also showed cross-protection against H5N1 viruses using trivalent seasonal influenza vaccine in mouse models [148] .

A preclinical study of a nasally delivered H5N1 vaccine containing an inactivated full-particle vaccine, rintatolimod as adjuvant and carboxy vinyl polymer base as vaccine base, was conducted by Japan's National Institute of Infectious Disease, with funding from the country's Ministry of Health, Labor and Welfare. Results showed that, in the group for which rintatolimod 20-fold was used, both IgG and IgA antibody titres had the highest values 2 weeks after final immunisation [153] .

Smallpox

Hemispherx stated in December 2001 that positive results had been obtained from animal studies on rintatolimod for the treatment of smallpox. It had suppressed vaccinia virus lesions at very low doses, but it appears that development for this indication has been discontinued.

Zika virus infection

In February 2016, Hemispherx announced its intention to explore the intranasal use of Ampligen® in non-pregnant patients with Zika virus infection. The study aims to establish whether or not Ampligen® could decrease Zika viral load in blood and other body fluids in patients, could shorten the time period during which the virus may be transmitted, and/or could decrease viral related tissue pathology [154] .

Cancer indications

As of June 2021, rintatolimod was launched in the US for the treatment of malignant melanoma and renal cell carcinoma.

In December 2014, Hemispherx reported that it is developing rintatolimod as a therapeutic complement to a new molecular class of anti-tumour drugs, immune checkpoint inhibitors or PD-1 (Programmed Death) inhibitors. The company is developing on-going antitumor programs in collaboration with Georgia Regents University (GRU) Cancer Centre and the University of Pittsburgh (UP). Preclinical studies conducted at GRU showed that a dsRNA analogue of rintatolimod had significantly increased survival in animal tumours when administered in combination with PD-1 inhibitors and in follow on animal experiments with rintatolimod demonstrated anti-tumour properties similar to those of typical PD-1 inhibitors with a resultant long term survival advantage in mouse melanoma. Rintatolimod and PD-1 treated mice were resistant to re-challenge with viable melanoma cells in the absence of drug (s) indicating a memory effect, which is most likely mediated by anti-melanoma cytotoxic CD8+ cells. Research conducted at UP showed that rintatolimod as a component to help modify the immunological micro environment around tumours to boost anti-tumour response. The data obtained provides basis for the combination of rintatolimod with PDL1 blockers and PD-1 blockers. The company believes that additional clinical trials will be required to establish whether these findings translate to enhanced survival or other clinical benefit in patients with malignant melanoma, metastatic renal cancer or other conditions [155] . As at July 2017, AIM ImmunoTech is planning clinical trials for cancer, including renal cell carcinoma and metastatic melanoma. Ampligen had a positive modulating effect on the PD-1/PD-L1/PD-L2 system in human ovarian and colorectal cancers [1] [156] .

In October 2018, Hemispherx Biopharma signed a clinical trial agreement with Roswell Park, to conduct clinical studies of Ampligen, in combination with checkpoint inhibitors, for the treatment of three solid tumours, including urothelial carcinoma (bladder and associated structures), renal cell carcinoma and melanoma [67] [157] . In June 2018, the company also signed a memorandum of understanding (MoU) with Roswell Park Cancer Center to conduct a planned phase I/II study of Ampligen, in combination with checkpoint inhibitors, in solid tumours [56] [158] .

Hemispherx Pharma has stated that the company is collaborating with several cancer centres that are conducting clinical trials of rintatolimod as an adjuvant in various cancer indications. The centres include the University of Washington, the Abramson Cancer Center at the University of Pennsylvania and the University of Pittsburgh [159] .

Breast cancer

In September 2023, AIM ImmunoTech announced plans to initiate a phase II trial to determine if a Chemokine-Modulating (CKM) Regimen including rintatolimod may be a safe and effective alternative to pembrolizumab [see ADISInsight drug profile800034086] or in addition to pembrolizumab/NAC for triple-negative breast cancer [160] .

As of November 2022, AIM ImmunoTech in collaboration with Roswell Park Cancer Center initiated a phase II trial for rintatolimod in combination with pembrolizumab, in patients with metastatic triple negative breast cancer (AIM ImmunoTech pipeline; November 2022) [129] .

In February 2023, Roswell Park Cancer Institute and National Cancer Institute completed a phase I trial that evaluated the safety, tolerability and efficacy of combination of rintatolimod and chemokine modulation therapy (celecoxib, recombinant interferon alfa-2b) as a neoadjuvant therapy with standard chemotherapy for the treatment of early-stage breast cancer (I 73718; NCI-2019-05299; I 73718; NCT04081389). The open-label, single group trial initiated in December 2019 enroled 9 patients in the US [161] . In September 2019, AIM ImmunoTech announced that it has received FDA authorisation to proceed with the phase I study of chemokine modulation plus neoadjuvant chemotherapy in patients with early-stage triple negative breast cancer (TNBC) using rintatolimod. The study will be conducted to evaluate the safety and tolerability of rintatolimod in combination with celecoxib with or without Intron A, and chemotherapy [162] . In November 2022, initial results from the trial were released by Aimmune Therapeutics [163] . In December 2022, company presented data from the trial at the 45th Annual San Antonio Breast Cancer Symposium (SABCS-2022) [164] . In September 2023, the company released updated efficacy data from the trial [160] .

In January 2019, Hemispherx Biopharma in collaboration with Roswell Park Cancer Center initiated a phase I study of rintatolimod in combination with pembrolizumab, in patients with metastatic triple negative breast cancer, who will undergo a pre-treatment biopsy (62218; NCT03599453). The trial was designed to evaluate the increase of CD8+ infiltration into tumour microenvironment after pre-treatment CKM regime comprising rintatolimod, celecoxib and recombinant interferon alfa-2b. The trial completed enrolment of eight patients in the US [165] [166] [167] [168] [169] [170] . In April 2022, data from the trial was released by AIM ImmunoTech [171] .

In June 2014 the University of Washington completed the phase I/II study began in the US which is evaluating Ampligen® as an adjuvant (with HER2 vaccination) in breast cancer (NCT01355393). The trial was initiated in August 2011, and enrolled 50 patients in the US [172] [173] .

Colorectal cancer

In January 2022, Roswell Park Cancer Institute and Merck Sharp & Dohme withdrew a phase IIa open-label trial prior enrolment which was designed to evaluate the safety and efficacy of intravenous infusion of rintatolimod in combination with pembrolizumab in patients with advanced, metastatic, unresectable colorectal cancer that is refractory to other treatment in the US (NCT04119830). The company withdrew the trial due to implementation related issues [174] .

In April 2018, Roswell Park Cancer Institute, in collaboration with National Cancer Institute (NCI), initiated a phase IIa trial that evaluated the safety and efficacy of rintatolimod, in combination with celecoxib and recombinant interferon alfa-2b [see AdisInsight drug profiles 800006795 and 800009995, respectively], in patients with colorectal cancer, metastatic to the liver (I 52917; NCI-2017-02471; P30CA016056; NCT03403634). The open-label study was initiated in April 2018, and enrolled 19 patients in the US [175] . The study was completed in August 2021, but reinitiated. In April 2022, AIM ImmuoTech announced results from the ongoing phase IIa trial [176] .

In January 2018, Hemispherx Biopharma, in collaboration with Roswell Park Cancer Institute, terminated a phase I/II trial of rintatolimod, in combination with celecoxib and interferon, in patients with recurrent colorectal cancer (NCT01545141; 10-131). The open-label, parallel, randomised trial intended to enrol approximately 50 patients in the US [177] [159] .

Pancreatic cancer

In February 2021, the European Medicines Agency granted orphan drug designation to rintatolimod for the treatment of pancreatic cancer. AIM ImmunoTech announced that NV Hemispherx Biopharma Europe (subsidiary of AIM ImmunoTech), received formal notification from the European Commission (EC) approving the company’s orphan medicinal product application. Earlier in the same month, the Committee for Orphan Medicinal Products (COMP) of the EMA recommended orphan drug designation for rintatolimod [178] .

In December 2020, the US FDA granted orphan drug designation status to rintatolimod for the treatment of pancreatic cancer [179] .

In October 2021, AIM ImmunoTech submitted an application for Fast Track status with the US FDA for locally advanced or metastatic late-stage pancreatic cancer when rintatolimod is added to standard of care [180] .

In January 2024, AIM ImmunoTech initiated a phase II trial of rintatolimod for the treatment of pancreatic cancer (NCT05494697). This randomized, open-label, controlled study is designed to evaluate the efficacy and safety of Ampligen® compared to control group/no treatment following FOLFIRINOX in subjects with locally advanced pancreatic adenocarcinoma, enrolled 90 patients in USA and may expand to Europe, Netherlands [181] [182] . In January 2024, AIM ImmunoTech announced that it has received authorization from the Erasmus Medical Center Ethics Committee to open a European site for the ongoing phase II study (AMP-270) of Ampligen as a therapy for locally advanced pancreatic cancer [183] . Earlier, In April 2022, AIM ImmunoTech published positive data from a single-center named patient program indicating that patients receiving Ampligen had a longer median survival time than matched historical controls. Patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with Ampligen at 2 doses per week with 400 mg per infusion. The phase II clinical trial of Ampligen (AMP 270) is planned to be a randomized, open-label, controlled, parallel-arm study with the primary objective of comparing the efficacy of Ampligen versus a no treatment control group following FOLFIRINOX for subjects with locally advanced pancreatic adenocarcinoma. Secondary objectives of the study include comparing safety and tolerability [184] . In March 2022, the US FDA lifted clinical hold from an Investigational New Drug application of AIM ImmunoTech to conduct the phase II study of the rintatolimod (Ampligen) as a therapy for locally advanced or metastatic late-stage pancreatic cancer. Earlier the FDA placed the study on clinical hold in November 2021 and provided valuable feedback on the study design. Company submitted response to the clinical hold in February 2022. In October 2021, AIM ImmunoTech submitted the IND. The trial will be conducted in the Europe and the US and intends to enroll approximately 90 patients [185] [180] [186] [186] [187] . Based on the data of this trial, the company intends to submit a new drug application for use of rintatolimod (Ampligen) in the treatment of pancreatic cancer [72] .

In September 2020, AIM announced intention to obtain US FDA's breakthrough designations. The company also announced intention to file dual orphan drug status applications with the US FDA and the EMA for use of rintatolimod (Ampligen) in the treatment of late-stage pancreatic carcinoma in the US and in the EU [188] .

In February 2021, the Dutch Health and Youth Care Inspectorate (IGJ) has approved treatment for six pancreatic cancer patients as part of a new, follow-up Early Access Program (EAP) at Erasmus Medical Center in the Netherlands. Based on the authorisations, the company intends to treat up to 16 pancreatic cancer patients with rintatolimod under the EAP [189] [190] .

In February 2018, Ampligen is available in Europe under an Early Access Programme. In August 2018, Hemispherx Biopharma released initial 500 vials of rintatolimod of 2,100 vial stock order from myTomorrows for pancreatic cancer Early Access Program (EAP) in Netherlands. In February 2019, company extended its Early Access Program for Ampligen for the treatment of pancreatic cancer at the Erasmus Medical Center in the Netherlands. The EAP is approved for the treatment of pancreatic cancer by the Dutch Health Inspectorate for two year. The company intends to expand the early access programme to other European countries and Canada. As of February 2019, 43 patients have been treated under this programme. As of August 2019, phase I development of rintatolimod for the treatment of pancreatic cancer is underway in Netherlands through early access programme. The candidate was well tolerated during the programme (AIM ImmunoTech pipeline, August 2019). In September 2020, positive efficacy data from the programme were reported by AIM ImmunoTech [191] [188] [15] . In February 2021, updated efficacy data from the trial were released by AIM ImmunoTech [192] [178] [167] [193] [156] [194] [166] [195] [56] [196] . In October 2021, AIM ImmunoTech announced data from the Erasmus MC early-access program which supported IND application and Fast Tack status application to the US FDA [180] . In March 2022, the company released updated pharmacodynamics and efficacy data from the trial [197] . In March 2024, updated pharmacodynamics data from the program was released by the company [198] .

In January 2024, AIM ImmunoTech, in collaboration with Erasmus Medical Center, initiated the phase Ib/II DURIPANC trial to evaluate the safety and efficacy of rintatolimod in combination with durvalumab [see ADISInsight drug profile800037095] in patients with metastatic pancreatic ductal adenocarcinoma (NCT05927142; EudraCT2022-003780-23; NL83224.078.22). The exploratory, non-randomized, open-label, single center study intends to enrol approximately 43 patients in the Netherlands [199] . The primary objective of the phase Ib portion is to determine the safety of the combination therapy. The primary objective of the phase II portion is to determine the clinical benefit rate of the combination therapy. In February 2024, the first patient was dosed in the trial [200] .

In March 2022, AIM ImmunoTech released preclinical data evaluating rintatolimod in pancreatic ductal adenocarcinoma cell lines [201] .

Prostate cancer

In January 2024, Hemispherx Biopharma in collaboration with National Cancer Institute and Roswell Park Comprehensive Cancer Center reinitiated a phase II trial of combination of rintatolimod and aspirin with or without recombinant interferon alfa-2b (interferon [IFN]-alpha) [202] . In February 2023, Hemispherx Biopharma in collaboration with National Cancer Institute and Roswell Park Comprehensive Cancer Center suspended a phase II trial of combination of rintatolimod and aspirin with or without recombinant interferon alfa-2b (interferon [IFN]-alpha) due to drug supply issue (I 77318; NCI-2019-01192; P30CA016056; NCT03899987). The phase II trial designed to evaluate the safety and immunomodulatory effectiveness of combination of rintatolimod and aspirin with or without recombinant interferon alfa-2b (interferon [IFN]-alpha) in patients with prostate cancer before surgery. The randomised open-label trial was initiated in November 2019 and enrol approximately 30 patients in the US [203] . In January 2024, Roswell Park Cancer Institute presented interim pharmacodynamics and safety data from the phase II trial in prostate cancer at the 2024 Genitourinary Cancers Symposium (ASCO-GeCS-2024) [202] .

In August 2019, Hemispherx Biopharma reported approval of an IND application for a prospective phase II trial of rintatolimod. The trial will be conducted in collaboration with Roswell Park Comprehensive Cancer Center and will evaluate neoadjuvant conditioning of prostate cancer with rintatolimod as a component of chemokine modulation with or without interferon-alpha 2b. The company also received approval from the Institutional Review Board (IRB) to conduct the trial. In March 2019, Hemispherx Biopharma submitted the IND. As at March 2019, preclinical development is underway in the US [166] [193] .

Ovarian/Peritoneal cancer

The University of Pittsburgh initiated a phase I/II trial to evaluate the safety and efficacy of autologous alpha type-1 polarised dendritic cell vaccine in combination with a systemic chemokine modulation regimen, consisting of rintatolimod, celecoxib and interferon-α-2b, as adjuvant therapy, following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, in patients with peritoneal cancer (NCT02151448). The trial will enrol approximately 168 patients from the US. The primary endpoint is to determine whether this combination immunotherapy can increase time-to-progression and whether this treatment regimen is safe. The study has enrolled 45 patients as of February 2019 [167] [204] .

The Abramson Cancer Center at the University of Pennsylvania is conducting a phase I/II trial of an autologous oxidized tumour cell lysate vaccine with rintatolimod as an adjuvant in ovarian, fallopian tube and primary peritoneal cancer (NCT01312389). Enrolment of an estimated 29 patients in the US was completed in April 2012 [205] .

In April 2011, Quest PharmaTech and Hemispherx Biopharma announced a clinical development arrangement for a planned 30-patient trial of oregovomab in combination with rintatolimod as a vaccine enhancer [206] . Under the terms of agreement, the costs will be shared by both companies. The trial was expected to begin in Canada and the US in 2011 but no recent development has been reported [207] .

The University of Washington Tumor Vaccine Group in the USA conducted a preclinical study in a transgenic mouse breast cancer model, which showed that rintatolimod acts as a potent cancer vaccine adjuvant when combined with an antitumour peptide vaccine. The results were reported in April 2011 [208] .

Hemispherx has completed phase II development and received clearance from the US FDA for a phase III study in patients with renal cell carcinoma. Clinical trials have also been conducted in patients with malignant melanoma. However, Hemispherx has stated that certain studies to date have not been well-controlled and additional tests will be necessary.

Rintatolimod demonstrated synergistic antitumor and antiviral activity when combined with human interferons in various studies [104] .

Investigator sponsored trial

In February 2019, the UPMC Hillman Cancer Center (formerly the University of Pittsburgh Cancer Institute) in collaboration with Merck and Hemispherx Biopharma initiated a phase I/II trial to evaluate the efficacy, safety of rintatolimod (IP, 200mg)in combination with cisplatin (IP, 50 mg/m2) and pembrolizumab (IV, 200mg) in patients with recurrent, platinum sensitive ovarian cancer (NCT03734692; HCC 18-087). In June 2019, the first patient was treated in the trial [209] . The open-label trial intends to enrol approximately 45 patients in the US [210] [211] . In March 2022, AIM ImmunoTech announced that phase I part of the trial was completed and enrolment in the phase II part was initiated and released the efficacy data from the trial [165] [212] .

In September 2020, University of Pittsburgh, in collaboration with Roswell Park Cancer Institute, Hemispherx Biopharma and National Cancer Institute, suspended a phase I/II trial which was investigating the addition of cisplatin to an investigational dendritic cell vaccine with or without an investigational drug combination of rintatolimod, interferon alpha-2b (IFN), and oral celecoxib, to evaluate the effect on recurrent ovarian cancer. The reasons for suspension was not disclosed (NCT02432378; 11-128; 5P01CA132714). The randomised, open-label trial, which was initiated in July 2015, intended to enrol approximately 25 patients in the US. Enrolment in phase II portion is expected to commence in September 2020. In November 2018, the trial had enrolled 10 patients in the phase I portion of the study. The combination therapy showed positive survival data, in patients with stage 4 ovarian cancer. In January 2022, data were released by the company, and got published in the American Association for Cancer Research publication, Clinical Cancer Research [213] [214] [215] [216] .

In preclinical studies of SARS-CoV-1 in mouse models, a protective effect was exhibited by rintatolimod. Virus lung titers were below detectable limits. The drug led to a rapid decline of virus in the lungs compared with untreated animals with a 100% survival outcome versus 100% death rate in the control group [104] .

Preclinical data demonstrated that, in explant culture models, rintatolimod activated the TLR3 pathway and promoted an accumulation of killer T cells. However, unlike the other two TLR3 agonists (poly IC and natural double stranded RNA), it did not accumulate regulatory T cell (Treg). This can aid in creating an enhanced tumour microenvironment for checkpoint blockage therapy [18] . In preclinical models and human tumour explants demonstrated that rintatolimod is a TLR3 restricted and targeted modulator of “hot” tumour microenvironments [168] .

Financing information

The National Cancer Institute has awarded $US14.5 million to Roswell Park to fund five immuno-oncology clinical trials. [217]

In October 2019, AIM immunotech raised approximately $US10 million from the public markets to support the clinical development of rintatolimod [218] .

In September 2019, the US Department of Defense granted $US 8.32 million fund in another "Breakthrough Award" to Moffitt Cancer Center for a Phase 2 clinical study of a combination of therapies with rintatolimod in patients with brain-metastatic breast cancer (BMBC). Roswell Park Comprehensive Cancer Center also received its own Department of Defence funded Breakthrough Award of $SU 6.42 million to study Ampligen in the treatment of BMBC [219] .

In February 2017, Hemispherx Biopharma announced the registered direct offering worth $US1 million following the definitive agreements with various investors. The proceeds of the offering will be used to cover expenses related to manufacturing of rintatolimod and for preparation of technology transfer opportunities [220] .

In August 2016, Hemispherx Biopharma entered into definitive agreements with two institutional investors for an offering of shares of common stock with gross proceeds of approximately $US5 million in a registered direct offering. The net proceeds will be used by the company for the expenses related to manufacturing of rintatolimod [221] . In November 2010, Hemispherx was awarded grants totalling $US488 958 through the US Qualifying Therapeutic Discovery Project programme. Part of these funds will be used to support clinical development of rintatolimod in CFS [222] .

Manufacturing agreement

In July 2016, Hemispherx entered into an agreement with Avrio Biopharmaceuticals, to serve as an additional contract manufacturer of rintatolimod [223] .

Patent Information

In November 2023, AIM ImmunoTech announced that rintatolimod was granted patent no. 11,813,279 titled "Compositions for cancer therapy and methods" and Patent no. 11,813,281 titled "Methods for improving exercise tolerance in myalgic encephalomyelitis patients" by the US patent office which are valid through 2039 [224] .

As of August 2023, AIM ImmunoTech reported that rintatolimod has been granted patent No. 2022/01079, titled “Compositions and Methods Useful for Ebola Virus Infection” by the South African Patent and Trademark Office (CIPC) [225] .

In January 2023, AIM ImmunoTech announced that the Netherlands Patent Office (Octrooicentrum Nederland) has granted a utility patent covering rugged dsRNA, a double-stranded RNA product related to Ampligen® (rintatolimod), which claims cover, among other aspects, compositions and compositions for use in the prevention or treatment of COVID-2019. The new patent broadens AIM’s existing portfolio for COVID-2019 treatments to include rugged dsRNA [226] .

In June 2022, AIM Immunotech announced that the Netherlands Patent Office (Octrooicentrum Nederland) issued patent no. 2 027 383 (a utility patent) covering rintatolimod and other AIM developed dsRNA products for use in the prevention or treatment of SARS-CoV-2 virus infection, including COVID-19 infections, with a base patent term extending until 2041. The patent is also directed to a composition comprising a vaccine against SARS-CoV-2 virus and rintatolimod designed to, in part, provide expanded immunity against future variants and also provide a similar response enhancing natural immunity post-infection, where rintatolimod is administered as an early onset intranasal therapy [227] .

In September 2021, AIM Immunotech filed a provisional patent application for rintatolimod as a potential early-onset intranasal therapy designed to enhance and expand infection-induced immunity, epitope spreading, cross-reactivity and cross-protection in patients exposed to a wide range of RNA respiratory viruses, such as influenza, rhinoviruses and SARS-CoV-2. The filing concerns the early-stage administration of rintatolimod following active viral replication after a respiratory virus has entered a person’s nasal passages [228] .

In August 2021, AIM ImmunoTech filed a provisional patent application for the use of rintatolimod both as intranasal and intravenous therapy for the treatment of post-COVID-2019 cognitive dysfunction [229] .

In June 2021, AIM ImmunoTech received patent protection for rintatolimod for Cancer therapy in combination with checkpoint blockade inhibitors in Netherlands. The patent expires December 2039, or 20 years from the date of filing [230] .
In June 2020, AIM ImmunoTech announced the filing of provisional patent application for the use of rintatolimod in the treatment of COVID-19 induced chronic fatigue [231] .

In February 2020, AIM ImmunoTech announced the filing of three provisional patent applications related to rintatolimod against the Wuhan coronavirus infections. The three provisional patent applications include use of rintatolimod both alone and in combination with interferon as an early onset therapy for Wuhan coronavirus (COVID-19), rintatolimod as part of a proposed intranasal universal coronavirus vaccine that combines rintatolimod with inactivated Wuhan coronavirus (SARS-CoV-2), conveying immunity and cross-protection and a high-volume manufacturing process for rintatolimod [104] [120] .

In 2016, Hemispherx Biopharma was granted US patents 9 315 528 B2 and 9 315 538 for the composition of matter patent for rintatolimod in the US [232] [65] .

In September 2015, the European Patent Office granted Hemispherx Biopharma a patent (EP 2 340 307) titled "Double-Stranded Ribonucleic Acids with Rugged Physiochemical Structure and Highly Specific Biologic Activity". In June 2015, the European Patent Office issued a formal notification to grant a patent. This composition of matter patent covers a form of rugged dsRNA, which has reduced tendency to form branched dsRNA enabling high bioactivity and binding affinity to toll-like receptor 3 (TLR3). The patent also covers the formulations of rugged dsRNA and methods of treatment with the same. A total of 28 patents were granted in different countries in the EU, further to which the product will be protected up to 2029 and beyond [65] [233] [234] .

In May 2014, the US Patent and Trademark Office had issued an US patent 8 722 874 to Hemispherx, entitled "Double-stranded Ribonucleic Acids with Rugged Physiochemical Structure and Highly Specific Biologic Activity", covering a novel form of rugged dsRNA, pharmaceutical formulations containing the dsRNA, and methods of treatment using these formulations. The patent provides protection until at least 2029 [235] .

In January 2013, US Patent Office granted one patent in Singapore for the use of Ampligen® to initiate innate immunity and to treat or prevent viral infections and tumours.

In July 2011, Hemispherx Biopharma was granted a US patent no. 7 943 147 for the use of rintatolimod as a seasonal influenza vaccine adjuvant. The patent describes a method using intranasal rintatolimod with a seasonal influenza vaccine to enhance an immune response against a H5N1 avian influenza infection [236] .

The main US CFS/ME treatment patent for rintatolimod, patent number 6 130 206, expired in October 2017. The main patents covering HIV treatment, including patent number 4 820 696, 5 063 209, and 5 091 374, expired in April 2006, November 2008, and February 2009, respectively. The US patent number 5 593 973 covering rintatolimod for the treatment of hepatitis C expired in January 2014. The Ampligen® Trademark number 73/617 87 was renewed through December 2018.

In May 2004, Hemispherx filed an expanded US patent application covering the use of rintatolimod for the potential treatment and prevention of SARS and emerging viruses. Hemispherx has been issued certain patents on the use of rintatolimod alone and rintatolimod in combination with certain other drugs including AZT, ddI, ddC, interferon and/or IL-2, for the treatment of HIV.

The original US composition of matter patent for rintatolimod was issued to the Johns Hopkins University in the early 1970s and was exclusively licensed to Hemisphere Biopharma. This patent has since expired [235] .

Drug Properties & Chemical Synopsis

  • Route of administration Intradermal, Intranasal, Intraperitoneal, IV
  • Formulation Infusion, Spray, unspecified
  • Class Adjuvants, Antineoplastics, Antiretrovirals, Antivirals, Oligonucleotides
  • Target HIV replication; Interferon; Ribonuclease; RNA synthesis; Toll-like receptor 3; VP35 protein
  • Mechanism of Action HIV replication inhibitors; Immunostimulants; Interferon stimulants; Ribonuclease stimulants; RNA synthesis inhibitors; Toll-like receptor 3 agonists; VP35 protein inhibitors
  • WHO ATC code

    J05 (Antivirals for Systemic Use)

    J05A-B (Nucleosides and nucleotides excl. reverse transcriptase inhibitors)

    J05A-X (Other antivirals)

    L03A (Immunostimulants)

    N07 (Other Nervous System Drugs)

  • EPhMRA code

    J5 (Antivirals for Systemic Use)

    J5B1 (Viral hepatitis products)

    J5B4 (Influenza antivirals)

    J5C1 (Nucleoside and nucleotide reverse transcriptase inhibitors)

    L3A (Immunostimulating Agents Excluding Interferons)

    N7 (Other CNS Drugs)

  • Chemical name [(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate;[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-oxo-3H-purin-9-yl)oxolan-2-yl]methyl dihydrogen phosphate;[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
  • Molecular formula C28 H40 N9 O25 P3
  • SMILES P(=O)(O)(O)OCC1OC(C(C1O)O)N1C=CC(=NC1=O)N.P(=O)(O)(O)OCC1OC(C(C1O)O)N1C=NC2C(N=CNC1=2)=O.P(=O)(O)(O)OCC1OC(C(C1O)O)N1C=CC(NC1=O)=O
  • Chemical Structure
  • CAS Registry Number 38640-92-5

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

adenocarcinoma

Outcome Measure

Tumor necrosis factor alpha (TNF-alpha)

T-cell surface antigen CD4

T-cell receptor T3 delta chain (CD3d)

T-cell receptor CD3-epsilon (CD3e)

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

PSA

negative elongation factor complex member C/D

mitochondrially encoded cytochrome c oxidase II

MIP-1 alpha

Interleukin-8 (IL-8)

Interleukin-6 (IL-6)

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

Indoleamine 2, 3-dioxygenase 1 (IDO1)

CXCL9

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

CD3 gamma chain (CD3G)

C-X-C motif chemokine ligand 11

C-C motif chemokine ligand 22

C-C motif chemokine 5 (CCL5

C-C motif chemokine 4 (CCL4

1

2

2

2

3

2

1

1

1

1

1

1

2

2

1

1

2

2

2

1

1

1

adenocarcinoma

Brief Title

IFN-alpha 2

1

adenocarcinoma

Arm Group Description

Interferon Gamma (IFNg)

IFN-alpha 2

1

1

adenocarcinoma

Detailed Description

CKM

1

adenocarcinoma

Eligibility Criteria

Microsatellite Stable (MSS)

1

adult respiratory distress syndrome

Arm Group Label

IFN-alpha 2

1

adult respiratory distress syndrome

Outcome Measure

UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3

Toll Like Receptor 3 (TLR3)

ribonuclease L

MxA

ISG15

interferon regulatory factor 7

interferon regulatory factor 3

interferon induced with helicase C domain 1

Interferon Gamma (IFNg)

Interferon alpha (IFN-alpha)

eukaryotic translation initiation factor 2 alpha kinase 2

DEXD/H-box helicase 58

C-reactive protein (CRP)

ACE2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

adult respiratory distress syndrome

Brief Title

IFN-alpha 2

1

adult respiratory distress syndrome

Arm Group Description

IFN-alpha 2

1

adult respiratory distress syndrome

Detailed Description

UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3

Toll Like Receptor 3 (TLR3)

ribonuclease L

MxA

ISG15

interferon regulatory factor 7

interferon regulatory factor 3

interferon induced with helicase C domain 1

interferon induced transmembrane protein 3

interferon induced protein with tetratricopeptide repeats 1

Interferon Gamma (IFNg)

Interferon alpha (IFN-alpha)

eukaryotic translation initiation factor 2 alpha kinase 2

DEXD/H-box helicase 58

C-reactive protein (CRP)

2'-5'-oligoadenylate synthetase 2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

adult respiratory distress syndrome

Official Title

IFN-alpha 2

1

advanced breast cancer

Arm Group Label

HER2/ERBB2

1

advanced breast cancer

Outcome Measure

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

Interferon Gamma (IFNg)

IFN-alpha 2

HER2/ERBB2

CKM

1

1

1

1

1

1

advanced breast cancer

Brief Title

HER2/ERBB2

1

advanced breast cancer

Arm Group Description

IFN-alpha 2

HER2/ERBB2

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

2

1

1

advanced breast cancer

Detailed Description

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

PD-L1/CD274

PD-1/CD279

HER2/ERBB2

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

CKM

1

1

1

1

1

1

1

advanced breast cancer

Eligibility Criteria

PGR

HER2/ERBB2

Estrogen receptor alpha (ER alpha)

1

1

1

advanced breast cancer

Official Title

HER2/ERBB2

1

advanced breast cancer

Brief Summary

neuralized E3 ubiquitin protein ligase 1

HER2/ERBB2

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

1

1

1

appendiceal cancer

Outcome Measure

Tumor necrosis factor alpha (TNF-alpha)

SDF-1 alpha (CXCL12)

Interleukin-8 (IL-8)

Interleukin-6 (IL-6)

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

C-X-C motif chemokine ligand 11

1

1

1

1

1

1

1

1

carcinoma

Arm Group Label

IFN-alpha 2

1

carcinoma

Outcome Measure

Tumor necrosis factor alpha (TNF-alpha)

T-cell surface antigen CD4

T-cell receptor T3 delta chain (CD3d)

T-cell receptor CD3-epsilon (CD3e)

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

negative elongation factor complex member C/D

mitochondrially encoded cytochrome c oxidase II

MIP-1 alpha

Interleukin-8 (IL-8)

Interleukin-6 (IL-6)

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

Indoleamine 2, 3-dioxygenase 1 (IDO1)

CXCL9

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

CD3 gamma chain (CD3G)

C-X-C motif chemokine ligand 11

C-C motif chemokine ligand 22

C-C motif chemokine 5 (CCL5

C-C motif chemokine 4 (CCL4

1

2

2

2

2

2

1

1

1

1

1

2

2

1

1

2

2

2

1

1

1

carcinoma

Brief Title

IFN-alpha 2

1

carcinoma

Arm Group Description

Interferon Gamma (IFNg)

IFN-alpha 2

1

1

carcinoma

Detailed Description

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

CXCR4

CXCL9

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

chemokine (C-C motif) receptor 6

C-X-C motif chemokine receptor 3

C-X-C motif chemokine ligand 11

C-C motif chemokine receptor 4

C-C motif chemokine ligand 22

C-C chemokine receptor type 5 (CCR5)

1

1

1

1

1

1

1

1

1

1

1

1

carcinoma

Eligibility Criteria

RAS

PD-L1/CD274

PD-1/CD279

Microsatellite Instable (MSI)

Epidermal growth factor receptor (EGFR)

1

1

1

1

1

chronic fatigue syndrome

Eligibility Criteria

Thyroid stimulating hormone beta (TSH)

Rheumatoid factor

1

2

colon cancer

Outcome Measure

Tumor necrosis factor alpha (TNF-alpha)

SDF-1 alpha (CXCL12)

Interleukin-8 (IL-8)

Interleukin-6 (IL-6)

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

C-X-C motif chemokine ligand 11

1

1

1

1

1

1

1

1

colorectal cancer

Arm Group Label

IFN-alpha 2

1

colorectal cancer

Outcome Measure

Tumor necrosis factor alpha (TNF-alpha)

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

Interleukin-8 (IL-8)

Interleukin-6 (IL-6)

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

HGPRT

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

C-X-C motif chemokine ligand 11

1

2

1

1

1

1

1

1

1

1

colorectal cancer

Brief Title

IFN-alpha 2

1

colorectal cancer

Arm Group Description

Interferon alpha (IFN-alpha)

IFN-alpha 2

1

1

colorectal cancer

Detailed Description

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

CXCR4

CXCL9

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

chemokine (C-C motif) receptor 6

C-X-C motif chemokine receptor 3

C-X-C motif chemokine ligand 11

C-C motif chemokine receptor 4

C-C motif chemokine ligand 22

C-C chemokine receptor type 5 (CCR5)

1

1

1

1

1

1

1

1

1

1

1

1

colorectal cancer

Eligibility Criteria

Vascular endothelial growth factor A (VEGF)

RAS

PD-L1/CD274

PD-1/CD279

Microsatellite Stable (MSS)

Microsatellite Instable (MSI)

KRAS

Epidermal growth factor receptor (EGFR)

1

1

1

1

1

1

1

2

colorectal cancer

Brief Summary

T-Cell differentiation antigen CD8

CKM

1

1

COVID-19 respiratory infection

Arm Group Label

IFN-alpha 2

1

COVID-19 respiratory infection

Outcome Measure

UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3

Toll Like Receptor 3 (TLR3)

ribonuclease L

MxA

ISG15

interferon regulatory factor 7

interferon regulatory factor 3

interferon induced with helicase C domain 1

Interferon Gamma (IFNg)

Interferon alpha (IFN-alpha)

eukaryotic translation initiation factor 2 alpha kinase 2

DEXD/H-box helicase 58

C-reactive protein (CRP)

ACE2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

COVID-19 respiratory infection

Brief Title

IFN-alpha 2

1

COVID-19 respiratory infection

Arm Group Description

IFN-alpha 2

1

COVID-19 respiratory infection

Detailed Description

UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3

Toll Like Receptor 3 (TLR3)

ribonuclease L

MxA

ISG15

interferon regulatory factor 7

interferon regulatory factor 3

interferon induced with helicase C domain 1

interferon induced transmembrane protein 3

interferon induced protein with tetratricopeptide repeats 1

Interferon Gamma (IFNg)

Interferon alpha (IFN-alpha)

eukaryotic translation initiation factor 2 alpha kinase 2

DEXD/H-box helicase 58

C-reactive protein (CRP)

2'-5'-oligoadenylate synthetase 2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

COVID-19 respiratory infection

Official Title

IFN-alpha 2

1

early breast cancer

Arm Group Label

HER2/ERBB2

1

early breast cancer

Outcome Measure

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

Interferon Gamma (IFNg)

IFN-alpha 2

HER2/ERBB2

CKM

1

1

1

1

1

1

early breast cancer

Brief Title

HER2/ERBB2

1

early breast cancer

Arm Group Description

IFN-alpha 2

HER2/ERBB2

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

1

1

1

early breast cancer

Detailed Description

HER2/ERBB2

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

1

1

early breast cancer

Eligibility Criteria

PGR

HER2/ERBB2

Estrogen receptor alpha (ER alpha)

1

1

1

early breast cancer

Official Title

HER2/ERBB2

1

early breast cancer

Brief Summary

neuralized E3 ubiquitin protein ligase 1

HER2/ERBB2

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

1

1

1

encephalomyelitis

Eligibility Criteria

Thyroid stimulating hormone beta (TSH)

Rheumatoid factor

1

2

fallopian tube cancer

Arm Group Description

Interferon Gamma (IFNg)

1

fallopian tube cancer

Outcome Measure

T-cell surface antigen CD4

T-cell receptor T3 delta chain (CD3d)

T-cell receptor CD3-epsilon (CD3e)

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

negative elongation factor complex member C/D

mitochondrially encoded cytochrome c oxidase II

MIP-1 alpha

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

Interferon alpha (IFN-alpha)

Indoleamine 2, 3-dioxygenase 1 (IDO1)

CXCL9

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

CD3 gamma chain (CD3G)

C-X-C motif chemokine ligand 11

C-C motif chemokine ligand 22

C-C motif chemokine 5 (CCL5

C-C motif chemokine 4 (CCL4

2

2

2

2

1

1

1

1

1

2

1

1

1

1

2

1

1

1

1

HIV-1 infections

Eligibility Criteria

T-cell surface antigen CD4

1

liver metastases

Arm Group Label

IFN-alpha 2

1

liver metastases

Outcome Measure

T-Cell differentiation antigen CD8

HGPRT

1

1

liver metastases

Brief Title

IFN-alpha 2

1

liver metastases

Arm Group Description

Interferon alpha (IFN-alpha)

IFN-alpha 2

1

1

liver metastases

Detailed Description

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

CXCR4

CXCL9

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

chemokine (C-C motif) receptor 6

C-X-C motif chemokine receptor 3

C-X-C motif chemokine ligand 11

C-C motif chemokine receptor 4

C-C motif chemokine ligand 22

C-C chemokine receptor type 5 (CCR5)

1

1

1

1

1

1

1

1

1

1

1

1

liver metastases

Eligibility Criteria

RAS

PD-L1/CD274

PD-1/CD279

Microsatellite Instable (MSI)

Epidermal growth factor receptor (EGFR)

1

1

1

1

1

male breast cancer

Arm Group Description

IFN-alpha 2

1

male breast cancer

Eligibility Criteria

PGR

Estrogen receptor alpha (ER alpha)

1

1

male breast cancer

Outcome Measure

T-Cell differentiation antigen CD8

IFN-alpha 2

CKM

1

1

1

malignant melanoma

Arm Group Label

IFN-alpha 2

1

malignant melanoma

Outcome Measure

T-Cell differentiation antigen CD8

1

malignant melanoma

Brief Title

IFN-alpha 2

1

malignant melanoma

Arm Group Description

PD-L1/CD274

PD-1/CD279

IFN-alpha 2

1

1

1

malignant melanoma

Detailed Description

PD-L1/CD274

PD-1/CD279

Interferon Gamma (IFNg)

Interferon alpha (IFN-alpha)

IFN-alpha 2

CKM

1

1

1

1

1

1

malignant melanoma

Eligibility Criteria

PD-1/CD279

1

malignant melanoma

Official Title

PD-L1/CD274

PD-1/CD279

IFN-alpha 2

1

1

1

malignant melanoma

Brief Summary

IFN-alpha 2

1

mesothelioma

Outcome Measure

Tumor necrosis factor alpha (TNF-alpha)

SDF-1 alpha (CXCL12)

Interleukin-8 (IL-8)

Interleukin-6 (IL-6)

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

C-X-C motif chemokine ligand 11

1

1

1

1

1

1

1

1

ovarian cancer

Arm Group Description

Interferon Gamma (IFNg)

1

ovarian cancer

Outcome Measure

T-cell surface antigen CD4

T-cell receptor T3 delta chain(CD3d)

T-cell receptor CD3-epsilon (CD3e)

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

negative elongation factor complex member C/D

mitochondrially encoded cytochrome c oxidase II

MIP-1 alpha

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

Interferon alpha (IFN-alpha)

Indoleamine 2, 3-dioxygenase 1 (IDO1)

CXCL9

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

CD3 gamma chain (CD3G)

C-X-C motif chemokine ligand 11

C-C motif chemokine ligand 22

C-C motif chemokine 5 (CCL5

C-C motif chemokine 4 (CCL4

2

2

2

2

1

1

1

1

1

2

1

1

1

1

2

1

1

1

1

peritoneal cancer

Arm Group Description

Interferon Gamma (IFNg)

1

peritoneal cancer

Outcome Measure

Tumor necrosis factor alpha (TNF-alpha)

T-cell surface antigen CD4

T-cell receptor T3 delta chain (CD3d)

T-cell receptor CD3-epsilon (CD3e)

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

negative elongation factor complex member C/D

mitochondrially encoded cytochrome c oxidase II

MIP-1 alpha

Interleukin-8 (IL-8)

Interleukin-6 (IL-6)

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

Interferon alpha (IFN-alpha)

Indoleamine 2, 3-dioxygenase 1 (IDO1)

CXCL9

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

CD3 gamma chain (CD3G)

C-X-C motif chemokine ligand 11

C-C motif chemokine ligand 22

C-C motif chemokine 5 (CCL5

C-C motif chemokine 4 (CCL4

1

2

2

2

2

2

1

1

1

1

1

2

3

1

1

1

2

2

2

1

1

1

prostate cancer

Arm Group Description

IFN-alpha 2

1

prostate cancer

Brief Title

IFN-alpha 2

1

prostate cancer

Detailed Description

CKM

1

prostate cancer

Outcome Measure

T-Cell differentiation antigen CD8

PSA

1

1

sarcoma

Arm Group Description

Interferon Gamma (IFNg)

1

sarcoma

Outcome Measure

T-cell surface antigen CD4

T-cell receptor T3 delta chain (CD3d)

T-cell receptor CD3-epsilon (CD3e)

T-Cell differentiation antigen CD8

SDF-1 alpha (CXCL12)

negative elongation factor complex member C/D

mitochondrially encoded cytochrome c oxidase II

MIP-1 alpha

Interleukin-10 (IL-10)

Interferon Gamma (IFNg)

Indoleamine 2, 3-dioxygenase 1 (IDO1)

CXCL9

Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10)

CD3 gamma chain (CD3G)

C-X-C motif chemokine ligand 11

C-C motif chemokine ligand 22

C-C motif chemokine 5 (CCL5

C-C motif chemokine 4 (CCL4

2

2

2

2

1

1

1

1

1

1

1

1

1

2

1

1

1

1

severe acute respiratory syndrome

Brief Summary

T-cell surface antigen CD4

1

severe acute respiratory syndrome

Eligibility Criteria

T-cell surface antigen CD4

1

triple negative breast cancer

Arm Group Description

IFN-alpha 2

2

triple negative breast cancer

Detailed Description

T-cell surface antigen CD4

T-Cell differentiation antigen CD8

PD-L1/CD274

PD-1/CD279

CKM

1

1

1

1

1

triple negative breast cancer

Eligibility Criteria

PGR

Estrogen receptor alpha (ER alpha)

1

1

triple negative breast cancer

Outcome Measure

T-Cell differentiation antigen CD8

IFN-alpha 2

CKM

1

1

1

Biomarker

Drug Name Biomarker Name Biomarker Function
Rintatolimod - AIM ImmunoTech 2'-5'-oligoadenylate synthetase 2 Detailed Description
ACE2 Outcome Measure
C-C chemokine receptor type 5 (CCR5) Detailed Description
C-C motif chemokine 4 (CCL4 Outcome Measure
C-C motif chemokine 5 (CCL5 Outcome Measure
C-C motif chemokine ligand 22 Detailed Description, Outcome Measure
C-C motif chemokine receptor 4 Detailed Description
C-reactive protein (CRP) Detailed Description, Outcome Measure
C-X-C motif chemokine ligand 11 Detailed Description, Outcome Measure
C-X-C motif chemokine receptor 3 Detailed Description
CD3 gamma chain (CD3G) Outcome Measure
chemokine (C-C motif) receptor 6 Detailed Description
Chemokine IFN-γ-inducible protein 10 (IP-10/CXCL10) Detailed Description, Outcome Measure
CHP1 Eligibility Criteria
Chromosome 17 Eligibility Criteria
CKM Brief Summary, Detailed Description, Outcome Measure
CXCL9 Detailed Description, Outcome Measure
CXCR4 Detailed Description
DEXD/H-box helicase 58 Detailed Description, Outcome Measure
Epidermal growth factor receptor (EGFR) Eligibility Criteria
ERBB3 Arm Group Description
Estrogen receptor alpha (ER alpha) Eligibility Criteria
eukaryotic translation initiation factor 2 alpha kinase 2 Detailed Description, Outcome Measure
Granulocyte-macrophage colony-stimulating factor (GM-CSF) Arm Group Description, Brief Summary, Detailed Description
H3P19 Eligibility Criteria
HER2/ERBB2 Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
HGPRT Outcome Measure
IFN-alpha 2 Arm Group Description, Arm Group Label, Brief Summary, Brief Title, Detailed Description, Official Title, Outcome Measure
Indoleamine 2, 3-dioxygenase 1 (IDO1) Outcome Measure
Interferon alpha (IFN-alpha) Arm Group Description, Detailed Description, Outcome Measure
Interferon Gamma (IFNg) Arm Group Description, Detailed Description, Outcome Measure
interferon induced protein with tetratricopeptide repeats 1 Detailed Description
interferon induced transmembrane protein 3 Detailed Description
interferon induced with helicase C domain 1 Detailed Description, Outcome Measure
interferon regulatory factor 3 Detailed Description, Outcome Measure
interferon regulatory factor 7 Detailed Description, Outcome Measure
Interleukin-10 (IL-10) Outcome Measure
Interleukin-6 (IL-6) Outcome Measure
Interleukin-8 (IL-8) Outcome Measure
ISG15 Detailed Description, Outcome Measure
KRAS Eligibility Criteria
Microsatellite Instable (MSI) Eligibility Criteria
Microsatellite Stable (MSS) Eligibility Criteria
MIP-1 alpha Outcome Measure
mitochondrially encoded cytochrome c oxidase II Outcome Measure
MxA Detailed Description, Outcome Measure
negative elongation factor complex member C/D Outcome Measure
neuralized E3 ubiquitin protein ligase 1 Brief Summary
neurensin 1 Eligibility Criteria
PD-1/CD279 Arm Group Description, Detailed Description, Eligibility Criteria, Official Title
PD-L1/CD274 Arm Group Description, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
PGR Eligibility Criteria
PSA Outcome Measure
RAS Eligibility Criteria
Rheumatoid factor Eligibility Criteria
ribonuclease L Detailed Description, Outcome Measure
SDF-1 alpha (CXCL12) Detailed Description, Outcome Measure
survival of motor neuron 1, telomeric Eligibility Criteria
T-Cell differentiation antigen CD8 Brief Summary, Detailed Description, Outcome Measure
T-cell receptor CD3-epsilon (CD3e) Outcome Measure
T-cell receptor T3 delta chain (CD3d) Outcome Measure
T-cell surface antigen CD4 Brief Summary, Detailed Description, Eligibility Criteria, Outcome Measure
Thyroid stimulating hormone beta (TSH) Eligibility Criteria
Toll Like Receptor 3 (TLR3) Detailed Description, Outcome Measure
transmembrane p24 trafficking protein 2 Eligibility Criteria
tubulin polymerization promoting protein Eligibility Criteria
Tumor necrosis factor alpha (TNF-alpha) Outcome Measure
UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3 Detailed Description, Outcome Measure
Vascular endothelial growth factor A (VEGF) Eligibility Criteria
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
COVID 2019 infections in combination with interferon (IFN) alpha-2b Combination therapy Phase I/II USA IV / unspecified AIM ImmunoTech, Roswell Park Cancer Institute, National Cancer Institute (USA) 04 Sep 2020
COVID 2019 infections - In volunteers Phase I Netherlands Intranasal / unspecified AIM ImmunoTech, Centre for Human Drug Research 08 Mar 2021
COVID 2019 infections - Prevention Phase I Netherlands Intranasal / unspecified AIM ImmunoTech, Centre for Human Drug Research 08 Mar 2021
Chronic fatigue syndrome - - Marketed USA IV / Infusion AIM ImmunoTech 21 Jun 2021
Chronic fatigue syndrome - - Registered Argentina IV / Infusion AIM ImmunoTech 23 Aug 2016
Chronic fatigue syndrome - - No development reported (Preregistration) European Union IV / Infusion AIM ImmunoTech 05 Sep 2006
Colorectal cancer in combination with celecoxib and interferon alfa-2b Combination therapy, Inoperable/Unresectable, Metastatic disease, Recurrent, Second-line therapy or greater Phase II USA IV / unspecified National Cancer Institute (USA), Roswell Park Cancer Institute 27 Mar 2018
Colorectal cancer - Metastatic disease, Neoadjuvant therapy, Recurrent Phase I/II USA IV / unspecified AIM ImmunoTech, Roswell Park Cancer Institute 01 Oct 2012
Ebola virus infections - - Preclinical USA Intranasal / Spray AIM ImmunoTech, United States Army Medical Research Institute of Infectious Diseases 05 Jul 2020
Ebola virus infections - - Preclinical Italy Intranasal / Spray AIM ImmunoTech 05 Jul 2020
HIV infections - - Marketed USA IV / Infusion AIM ImmunoTech 21 Jun 2021
Hepatitis B - - No development reported (II) USA IV / Infusion AIM ImmunoTech 05 Sep 2006
Influenza A virus infections Biodefence purposes - No development reported (Research) USA IV / unspecified AIM ImmunoTech 28 Apr 2020
Influenza virus infections - Combination therapy, In volunteers, Prevention Phase I/II USA Intranasal / unspecified AIM ImmunoTech 01 Apr 2012
Malignant melanoma - - Marketed USA IV / Infusion AIM ImmunoTech 21 Jun 2021
Malignant melanoma HLA-A2+ Refractory Melanoma Combination therapy, Second-line therapy or greater Phase II USA IV / Infusion AIM ImmunoTech, Roswell Park Cancer Institute 22 Aug 2022
Ovarian cancer - Adjuvant therapy Phase I/II USA IV / unspecified AIM ImmunoTech 01 Mar 2011
Ovarian cancer - Combination therapy, Late-stage disease, Neoadjuvant therapy, Recurrent, Second-line therapy or greater Suspended (I/II) USA Intraperitoneal / unspecified AIM ImmunoTech, University of Pittsburgh, Roswell Park Cancer Institute, National Cancer Institute (USA) 02 Sep 2020
Pancreatic cancer - Late-stage disease, Second-line therapy or greater Phase II Europe, USA IV / unspecified AIM ImmunoTech 18 Aug 2022
Pancreatic cancer control group / no treatment following FOLFIRINOX treatment Inoperable/Unresectable, Late-stage disease, Second-line therapy or greater Phase II USA IV / unspecified AIM ImmunoTech 27 Feb 2023
Pancreatic cancer in combination with durvalumab Combination therapy, Late-stage disease, Metastatic disease Phase I/II Netherlands IV / unspecified AIM ImmunoTech, Erasmus MC 09 Jan 2024
Pancreatic cancer Early access programme Late-stage disease Phase I Netherlands IV / unspecified AIM ImmunoTech 13 Aug 2017
Peritoneal cancer - Adjuvant therapy Phase I/II USA IV / unspecified AIM ImmunoTech 01 Jul 2014
Post acute COVID 19 syndrome aged 18-60 years - Phase II USA IV / unspecified AIM ImmunoTech 29 Jun 2023
Prostate cancer In prostate cancer patients before surgery Combination therapy, Late-stage disease, Neoadjuvant therapy Phase II USA IV / unspecified AIM ImmunoTech, Roswell Park Cancer Institute, National Cancer Institute (USA) 29 Nov 2019
Renal cell carcinoma - - Marketed USA IV / Infusion AIM ImmunoTech 21 Jun 2021
Smallpox - - Discontinued (Preclinical) USA IV / Infusion AIM ImmunoTech 08 Feb 2010
Triple negative breast cancer triple-negative breast cancer Combination therapy, Inoperable/Unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater Phase II USA IV / unspecified AIM ImmunoTech, Roswell Park Cancer Institute 07 Nov 2022
Triple negative breast cancer - Adjuvant therapy Phase I/II USA Intradermal / unspecified AIM ImmunoTech 01 Jul 2011
Triple negative breast cancer In combination with Chemokine modulation therapy and chemotherapy Combination therapy, Early-stage disease, Neoadjuvant therapy Phase I USA IV / unspecified National Cancer Institute (USA), Roswell Park Cancer Institute 06 Dec 2019
West Nile virus infections - - Discontinued (Preclinical) USA unspecified / unspecified AIM ImmunoTech 05 Jul 2020
Western equine encephalitis virus infections - - Discontinued (Preclinical) USA IV / unspecified AIM ImmunoTech 13 Apr 2015
Zika virus infection - - Discontinued (Preclinical) USA Intranasal / unspecified AIM ImmunoTech 05 Jul 2020

Orphan Status

Indication Patient Segment Country Organisation Event Date
Chronic fatigue syndrome - USA AIM ImmunoTech 09 Dec 1993
Chronic fatigue syndrome - European Union Hemispherx Biopharma Europe 31 Dec 1995
Ebola virus infections - European Union AIM ImmunoTech 11 May 2015
Ebola virus infections - USA AIM ImmunoTech 02 Nov 2022
HIV infections - USA AIM ImmunoTech 01 Dec 2013
Malignant melanoma - USA AIM ImmunoTech 01 Dec 2013
Pancreatic cancer - European Union Hemispherx Biopharma Europe 24 Feb 2021
Pancreatic cancer - USA AIM ImmunoTech 17 Dec 2020
Renal cell carcinoma - USA AIM ImmunoTech 01 Dec 2013

Commercial Information

Involved Organisations

Organisation Involvement Countries
Hemispherx Biopharma Originator USA
AIM ImmunoTech Owner USA
myTomorrows Market Licensee Canada, Europe, Turkey
GP Pharm Market Licensee Argentina, Latin America, Mexico
Emerge Health Market Licensee Australia, New Zealand
AstraZeneca Collaborator United-Kingdom
University of Alabama Collaborator USA
National Cancer Institute (USA) Collaborator USA
Merck & Co Collaborator USA
Shionogi Collaborator Japan
University of Washington Collaborator USA
Howard University Collaborator USA
National Institute of Neurological Disorders and Stroke Collaborator USA
University of Pennsylvania Collaborator USA
Roswell Park Cancer Institute Collaborator USA
University of Cagliari Collaborator Italy
Erasmus University Rotterdam Collaborator Netherlands
Erasmus MC Collaborator Netherlands
National Institute of Allergy and Infectious Diseases Collaborator USA
Centre for Human Drug Research Collaborator Netherlands
Swiss Department of Defence, Civil Protection and Sport Collaborator Switzerland
Lovelace Respiratory Research Institute Collaborator USA
hVIVO Collaborator United-Kingdom
United States Army Medical Research Institute of Infectious Diseases Collaborator USA
University of Nebraska Medical Center Collaborator USA
Bioclones Collaborator South Africa
University of Pittsburgh Collaborator USA
Millions Missing Canada Collaborator Canada
Georgia Regents University Collaborator USA
National Institute of Infectious Diseases Collaborator Japan

Licensing Availability

Licensing Organisation Available Indication Available Phase Region Date
AIM ImmunoTech - Unspecified - 17 Oct 2023

Brand Names

Brand Name Organisations Indications Countries
Ampligen AIM ImmunoTech Chronic fatigue syndrome Argentina, USA
Rintamod GP Pharm Chronic fatigue syndrome Latin America

Scientific Summary

  • Adverse Events Occasional: Chills; Dyspnoea; Fatigue; Fever; Flu-like symptoms; Flushing; Headache; Leucocytosis; Leucopenia; Muscle pain; Nausea; QT interval prolongation

Adverse Events

Cancer indications

The most common adverse events in a clinical trial with metastatic melanoma patients included myalgia, headache and fatigue [258] .

safety data from phase II trial of rintatolimod in patients with prostate cancer showed chemokine modulation (CKM) regimen was well tolerated with no Grade 3 or above adverse events (AEs) [202] [203]

In a phase IIa trial of rintatolimod in patients with colorectal cancer, the treatment was well tolerated. Of all enrolled patients (N=19), adverse events were noted in 74% of patients, with the most common being fatigue (58%). Grade 3 or higher adverse events were rare (5%). No tumor responses were seen [176] [175] .

In phase I study in breast cancer patients (n=6), chemokine modulation therapy (CKM) including rintatolimod with pembrolizumab was well tolerated [171] [169] .

Treatment with rintatolimod, in combination with interferon alpha-2b (IFN), and oral celecoxib, was safe and generally well tolerated, in patients (n=25) with advanced recurrent ovarian cancer, in a phase I/II trial. No major toxicities were reported. The 3 non-evaluable patients did not complete at least 3 cycles, due to platinum hypersensitivity reactions or port complications. Overall, the regimen was well tolerated, apart from the highest dose of IFNa. Most common toxicities for all grades were anemia (58%), hypomagnesemia (50%), hyponatremia (41.7%), arthralgia (41.7%), and fatigue (41.7%). There was one grade 4 hypomagnesemia (8.3%). Dose limiting toxicities of abdominal pain of grade 3 or more were noted in two patients who received 18MU IFNa (cohort 4) [213] [216] .

Breast cancer

Phase I

: Results from a phase I clinical trial in patients with breast cancer demonstrated that treatment was well-tolerated with mostly grade 1 or 2 treatment-related adverse events (TRAEs) without DLTs or delayed or immune-related toxicities. Grade 3 TRAEs included neutropenia (3/9) attributed to CKM (1/9) or paclitaxel (3/9), pneumonia (1/9) and anemia (1/9) attributed to AC. Additional pneumonia and skin squamous cell carcinoma in situ were observed, unrelated to study treatment. Paclitaxel- or AC-related toxicities were not higher than expected [164] [163] [161] .

Chronic fatigue syndrome (CFS)

Rintatolimod 400mg twice-daily for 40 weeks was generally well tolerated in a pivotal, multicentre (n = 12), randomised, double-blind, placebo-controlled phase III study in 234 patients with CFS. There were no significant differences in the frequency of missed dosages and withdrawals among patients receiving rintatolimod or placebo; however, a greater proportion of placebo patients had significant prolongation of the EKG QT interval compared with those who received rintatolimod [49] [248] .

In a AMP-511 expanded access programme (EAP) in patients with severely debilitating chronic fatigue syndrome, patients indicated they had experienced a reduction in fatigue (n=4), as measured via Patient-Reported Outcomes questionnaires, following 12 weeks of ampligen treatment [74] [63] .

HIV infections
During clinical trials in which HIV-infected patients received IV infusions of rintatolimod at dose levels of 10-570 mg/m2/dose, the most frequent adverse events were flushing, chills, fever, tight chest, dyspnoea, flu-like symptoms and nausea. All reactions were self-limiting and generally subsided after the infusion was completed. Infusions were usually accompanied by transient leucopenia and then leucocytosis. One patient who received rintatolimod 570 mg/m2 discontinued therapy after developing flu-like symptoms and fatigue [265] [270] [260] .

During combination therapy with zidovudine and rintatolimod, toxicity was similar to that caused by zidovudine alone [271] .

In a study that compared rintatolimod with placebo in zidovudine recipients, the total number of adverse events did not differ significantly between treatment groups [257] .

In HIV-1-positive patients undergoing structured treatment interruptions (STI) of HAART, adverse events associated with rintatolimod were mild and self-limiting. There was no incidence of insulin resistance, hyperlipidaemia, or adverse changes in lactic acid levels [252] .

Influenza virus infections

Results from a phase I/II trial showed that the intranasal use of rintatolimod and FluMist [see AdisInsight RDI profile800004972] was generally well-tolerated. No evidence of any increase in adverse effects related to higher dosage levels of rintatolimod or to the continued administration of rintatolimod during the second and third dual vaccinations was observed. The two-staged, randomised, double-blind trial assessed the immunogenicity and safety of intranasal FluMist administered sequentially with intranasal rintatolimod [146] [150] .

COVID-2019 infections and other respiratory viral diseases

Results from a phase II trial showed that rintatolimod was generally well-tolerated with no severe adverse events, no treatment-emergent adverse events (TEAEs) leading to death, and no severe TEAEs reported during the study. Six subjects (15.0%) in the rintatolimod group with TEAEs had mild TEAEs related to the study treatment. Two subjects in the rintatolimod (Ampligen) group had TEAEs leading to treatment discontinuation or interruption. More subjects in the Ampligen group compared to the placebo group reported TEAE (10 subjects, 25.0% vs. four subjects, 10.0%), however the majority of these were mild [96] [91] .

In the phase I trial evaluating intranasal ampligen in healthy subjects, the repeated intranasal dosing regimen was shown to be well tolerated in all tested dose levels. Safety and tolerability were monitored for 28 days after first dosing. No severe or serious AEs reported. Solicited local AEs were comparable across all treatment groups and placebo [115] . In the phase I AMP-COV-100 trial, 200 µg of intranasal rintatolimod was found to be safe in healthy participants with no serious adverse events reported [112] . Earlier, rintatolimod 75 µg, administered intranasally, was found to be safe in healthy volunteers in cohort one of the trial. No serious adverse events were reported. The randomised, prospective, double-blind trial intends to enrol approximately 40 healthy volunteers in four cohorts [111] [98] .

Pharmacodynamics

Summary

Coadministration of rintatolimod and a peptide cancer vaccine inhibited tumour growth to a significantly greater extent than the vaccine alone (p=0.002) in a transgenic breast cancer mouse model. Administration of rintatolimod with the vaccine inhibited tumour growth to a significantly greater extent than another vaccine adjuvant candidate, CpG ODN 2395 (a toll-like receptor-9 agonist); however, inhibition of tumour growth was not significantly different between rintatolimod plus vaccine and GM-CSF plus vaccine. Compared with the vaccine alone, addition of rintatolimod, CpG and GM-CSF inhibited tumour growth by 60%, 53% and 37%, respectively. In contrast, imiquimod failed to increase the antitumour activity of the vaccine [208] .

In preclinical studies involving rodents and non-human primates (monkeys), rintatolimod enhanced the activity of influenza vaccines by conferring increased cross-reactivity and cross-protection, against deadly viruses, including avian H5N1 influenza virus. The studies showed that the development of a universal vaccine was possible through simply administered nasal immunisation of seasonal vaccines in combination with rintatolimod to achieve immune enhancement by ‘epitope spreading’. The data demonstrated in animals and humans showed the generation of antibodies against highly pathogenic avian influenza viruses with high lethality in humans, ~60% for H5N1 and ~40% for H7N9, with super pandemic potential,with the ability to easily infect humans through antigenic shift obtained with retention of high lethality [147] .

Prostate cancer:

Phase II:

Pharmacodynamics data from phase II trial of rintatolimod in patients with prostate cancer showed there were no clinicopathological differences between the groups (N=5 Arm A, 3 Arm B, 3 Arm C). Eight patients (on Arms A and B) were analyzed for changes in cytotoxic T cell numbers (CTL-D: GrB+CD8+ T-cells) in the blood. In Arm A, the mean pre-CKM CTL-D was 35.5% (±23.2%) and post-CKM was 47.7% (± 32.5%), while in Arm B, respectively, 37.9% (±22.2%) vs 37.1% (± 21.6%). These changes were reflected in the increased CTL/Treg markers in the post-treatment samples of patients on Arm A. These data indicate the ability of the “complete CKM regimen” (Arm A) to selectively enhance the CTL effector function in circulating CD8+ T cells, without enhancing the Treg markers [202] [203]

Pancreatic cancer

The Erasmus MC early-access programme in pancreatic cancer patients demonstrated that rintatolimod treatment in pancreatic cancer patients enhanced peripheral immune activity at the transcriptomic and proteomic levels, particularly involving type 1 conventional dendritic cells (cDC1s) and T cells. Post-rintatolimod, the increased peripheral abundance of BTLA+XCR1+ cDC1s and CD4+SELL+ T cells correlated with improved clinical outcomes. Patients with stable disease exhibited pronounced overexpression of genes related to DC and T cell activation. The expression of immune checkpoints PD-L1 and PD-L2 decreased post-rintatolimod across all patients suggesting that rintatolimod infusions modulates PD-L1 and PD-L2 expression in the tumor microenvironment, while at the same time upregulating Ki67+CD4+ and Ki67+CD8+ T-cells [198] [197] [194] .

Results from a preclinical study conducted in pancreatic cancer mouse model showed that treatment with rintatolimod in combination with an anti-PD-L1 drug showed a significant synergistic increase in median survival over control (p = 0.029) [167] .

In in vitro studies conducted using three pancreatic ductal adenocarcinoma cell lines (CFPAC-1, MIAPaCa-2, and PANC-1), rintatolimod decreased the proliferation and migration ability of CFPAC-1 cells. In addition, it decreased the proliferation of MIAPaCa-2 cells and the migration of PANC-1 cells. However, it did not have a dual effect in MIAPaCa-2 and PANC-1 cells. Immunohistochemistry revealed that, TLR3 was highly expressed in CFPAC-1 cells, low expressed in MIAPaCa-2 and not expressed in PANC-1. Gene expression analysis revealed the upregulation of interferon-related genes, chemokines, interleukins and cell cycle regulatory genes. The heterogeneity of TLR3 expression was confirmed in human PDAC samples [201] .

Breast cancer

Phase I

: In a phase I trial, treatment with rintatolimod in triple negative breast cancer (TNBC) patients showed consistent (p=0.07) selective increase in CD8α (CTL marker) in on treatment tumour biopsies with concomitant decrease in CD8α in the blood (p=0.04) [164] [161] .

Results from in vitro studies demonstrated that in vitro treatment of peripheral blood mononuclear cells (PBMCs) from 15 CFS patients (mean average age 47.5 years and median age 46.1 years, 67% are female) with rintatolimod increased mean NK activity (NKCC) and median NK activity (NKCC) by 178% and 100%, respectively [87] .

Ebola virus infection

In preclinical studies in mouse model of Ebola virus, complete survival (100%) was observed at the lowest dose of 6mg/kg of rintatolimod, which was corresponding to human dose of approximately 400mg, during the 21 day treatment period. The survival rate lowered to 90% at higher dosages. A 100% death rate was observed in placebo-treated animals within seven days of infection [132] [133] .

In in vitro studies, rintatolimod indicated binding to VP35 and displacement of viral dsRNA with 50% inhibition at 1.1 µg/ml. Inhibitory concentrations of 4 µg/ml at 50% viral protection was similar to VP35 binding result. The EC50 of rintatolimod was very low relative to the rintatolimod serum levels achieved [138] .

Influenza virus infections

Preclinical data in macaque monkeys exposed to the most virulent forms of pandemic influenza (H5N1) showed that while standard human seasonal influenza vaccines alone had no benefit on H5N1 virus pathology and clinical status, these were highly effective against H5N1 influenza virus when co-administered with small doses of intranasal rintatolimod in a prophylactic setting. Additionally to increased cross-protection and cross-reactivity, rintatolimod may enhance immunity with higher IgA and IgG levels to provide a survival/therapeutic advantage in animal models, and has potential to protect against a phenomenon known as "antigenic drift" (when the pandemic virus can escape the preventive effect of the vaccine). This is well-established phenomenon with avian H5N1 virus that has mitigated the potential usefulness of various already manufactured influenza vaccines [244] .

Rintatolimod was combined with oseltamivir and with zanamivir and applied to cells in culture which had been infected with an H5N1 strain of highly pathogenic avian influenza (HPAI). Results showed that rintatolimod, oseltamivir, and zanamivir exhibited dose responses in the inhibition of the adverse effects of HPAI on cell cultures. At certain doses, furthermore, the combination of rintatolimod and oseltamivir showed synergistic inhibition of viral-induced cell destruction. Similar synergistic results were seen with the combination of rintatolimod and zanamivir [245] .

Rintatolimod reduced serum and liver viral DNA levels in ducks congenitally infected with duck hepatitis B virus, and had at least additive effects with ganciclovir. Rintatolimod had no effect on circulating duck HBsAg and viral replication returned to baseline levels after treatment discontinuation [266] .

COVID-2019 infections

Rintatolimod showed 100% survival rate at clinically achievable human dosage levels for severe acute respiratory syndrome (SARS) in animal experiments. in in vitro models, rintatolimod decreased SARS-CoV-2 viral yields by 90% at clinically achievable intranasal dosage [121] [120] .

The results from a phase I trial evaluating intranasal ampligen in healthy subjects support the promising potential in the ability of ampligen to inhibit respiratory viruses at the point of entry. The results demonstrated an increase in IL-6, IL-8, and TNF production for both ampligen and placebo after dosing. MCP-1 and RANTES, which are important immunomodulators peaked 3-24 hours after administration, mainly for 500 µg ampligen. At doses evaluated, intranasal Ampligen administration did not drive a significant change in nasal immune cell abundance [115] .

Ebola virus infections
In preclinical studies results showed treatment with rintatolimod enhanced innate immunological responses to ebola virus infection. VP35 is understood to sequester the dsRNA produced by EBOV during its replication, which inhibited the normal innate immune responses to viral infection. Ampligen protected mice from a lethal challenge by mouse adapted EBOV-Zaire and its associated weight loss. The 6 mg/kg doses, frequently used in AIM’s clinical trials, used in mouse model was easily achievable and well tolerated in humans. Ampligen appears to inactivate the EBOV lethal factor (EBOV VP35), which is believed to be responsible, in part, for the high mortality rate observed in humans, by acting as a competitive decoy [140]

Antimicrobial Activity

Summary

Rintatolimod induced expression of the physiologically functioning antiviral protection system (2-5A synthetase/RNase L system) in cells.

In vitro

, rintatolimod 9.7 µg/ml inhibited HIV. Rintatolimod is synergistic with multiple anti-HIV drugs. Combination indices were determined for 14 anti-HIV agents alone and in combination with rintatolimod using Dose Effect analyses and the CalcuSyn for Windows software. Rintatolimod was synergistic in combination with abacavir, zidovudine, zalcitabine, didanosine, stavudine, efavirenz, indinavir, ritonavir, nelfinavir and amprenavir. It was synergistic to antagonistic with lamivudine, delavirdine, nevirapine and saquinavir [254] .-related reduction of Molt-3 cell growth rate by 50%. It acted synergistically with a reverse transcriptase inhibitor and with an antisense oligonucleotide directed against the tat gene [272] .

Rintatolimod did not display any synergism against HIV in vitro when used in combination with didanosine. In contrast, synergism was demonstrated between rintatolimod and zidovudine at combination ratios ranging from 100 : 1 to 1 : 50 [259] . Rintatolimod also acted synergistically with zidovudine against zidovudine-resistant strains [271] .

The compound has been shown to inhibit human herpes virus-6 (HHV-6) infection in T lymphocytes at concentrations of 100 and 200 µg/ml [273] [274] , and is also active against rotavirus [262] .

Rintatolimod was equally active against wild-type HIV and HIV resistant to nevirapine, protease inhibitors and nucleoside reverse transcriptase inhibitors [254] .

Rintatolimod is synergistic with multiple anti-HIV drugs. Combination indices were determined for 14 anti-HIV agents alone and in combination with rintatolimod using dose effect analyses and the CalcuSyn for Windows software. Rintatolimod was synergistic in combination with abacavir, zidovudine, zalcitabine, didanosine, stavudine, efavirenz, indinavir, ritonavir, nelfinavir and amprenavir. It was synergistic to antagonistic with lamivudine, delavirdine, nevirapine and saquinavir [254] .

The effect of rintatolimod on duck hepatitis B (DBHV) replication in duck primary hepatocytes was compared with D-FMAU. Rintatolimod and D-FMAU inhibited DBHV DNA replication by 50% at concentrations of 0.34±0.06 and 0.0007±0.0001 µgm/L, respectively. Rintatolimod slightly inhibited the intermediate DBHV DNA at a concentration as high as 1.0 µg m/L. The DBHV replicative form was markedly suppressed in the presence of 0.1 µg m/L of D-FMAU. However, rintatolimod markedly inhibited DHBV RNA transcription, compared with D-FMAU. This inhibitory effect of rintatolimod continued after the compound was removed from the culture medium whereas the efficacy of D-FMAU did not [256] .

Drug Interactions

Summary

Immunogenicity

Summary

When co-administered with vaccine, rintatolimod boosted IgA antibody levels by up to 500%. Of the animals that were administered with rintatolimod, 80% survived viral challenge, while none in the placebo group survived [246] .

In a phase I/II trial, rintatolimod demonstrated broad immunological effects and displayed cross-reactivity in healthy volunteers which was also seen earlier against avian influenza strains. The combination therapy utilised in the trial produced specific secretory IgA antibody responses of a minimum 4-fold over baseline against at least one of the homologous vaccine strains in the vaccine in 92% of the volunteers. There was induction of cross-reactive secretory IgA antibodies against highly pathogenic avian influenza strains H5N1, H7N9, and H7N3, all with pandemic potential for humans. Updated results showed that the combination regimen generated antibodies against influenza subtypes not present in the seasonal vaccine. The two-staged, randomised, double-blind trial assessed the immunogenicity and safety of intranasal FluMist [see AdisInsight RDI profile [500004972]] administered sequentially with intranasal rintatolimod [146] [147] [150] .

Therapeutic Trials

Ten patients with metastatic melanoma were treated with rintatolimod in an open-label phase I/II trial. The drug was administered intravenously at a low dose (80mg) to one patient, and at a high dose (200-1000mg) to nine patients, over 30-60 min twice-weekly for 3-111 weeks. Two of the patients receiving high dose therapy achieved a complete response. Both received maintenance therapy for at least 12 months following this and have remained in complete response without further therapy at 21 and 91 months [258] .

Pancreatic cancer:

In an Erasmus MC early-access programme in pancreatic cancer patients (n=27) statistically significant clinical data was observed where the median PFS (13 months) and overall survival (19 months) was significantly longer with rintatolimod compared to both matched controls and the subset of matched controls (5 and 8.6 months, respectively). The hazard ratio was 0.51 and 0.52, respectively [197] . Earlier, the overall survival of the rintatolimod (Ampligen)-treated cohort was 19.2 months from the start of FOLFIRINOX, compared to 12.5 months in the historical control group, for an increase in survival of 6.7 months. Additionally, several patients were still alive more than three years later [180] .Previously, results from a Early Access Program (EAP) in patients with locally advanced and/or metastatic pancreatic cancer showed that treatment with rintatolimod following the current standard of care for pancreatic cancer (FOLFIRINOX) yielded an overall survival of 19 months, 7.9 months greater than FOLFIRINOX treatment alone. Rintatolimod achieved statistically significant positive results with median survival of 200%, which was two-fold higher compared with the historical control arm matched for age, gender, stage of disease, and number of cycles of Folfirinox chemotherapy. [178] [188] [194] . Results from 26 patients in an early access programme in pancreatic cancer revealed stable disease in six patients and regression of metastasis in two patients. Earlier results from 24 evaluable patients indicated survival of more than one year, for four of 24 patients with locally advanced or metastatic disease, and treated with rintatolimod. An additional four patients on combination therapy of rintatolimod and palliative chemotherapy survived for more than one year. However, there were 15 casualties in this group of patients within seven months of rintatolimod therapy. Of the five resected patients, two died on rintatolimod, 24 and 27 months respectively, following resection. The remaining three patients are still alive with a mean survival of 26 months after resection and adjuvant rintatolimod treatment. Results from the 26 patients treated under the programme [193] [167] .

Preclinical data showed that treatment with rintatolimod in pancreatic cancer cells increased the expression of MHC class I and II genes significantly. All class I genes were increased in a gradient fashion. The HLA-B gene was increased more than 20 times after treating with rintatolimod. Cytokine and chemokine production was also significantly increased in pancreatic cancer cells treated with rintatolimod. CXCL10 was increased more than 200 times after rintatolimod treatment. All these cytokines are important in monocyte and macrophage activation. They are also known to act as chemoattractants for T cells, NK cells, and dendritic cells. Interestingly, treating with rintatolimod did not induce the expression of CXCL12, which plays an important role in increasing the metastatic abilities of cancerous cells. Rintatolimod induced an innate and an adaptive immune response in pancreatic cancer cells. The secreted cytokines attract immune cells including macrophages, NK cells, T cells, and B cells. Importantly, treating with rintatolimod did not stimulate the metastasis-related genes. Treatment with rintatolimod did not upregulate the expression of TGFβ1 which caused chronic fibrosis to the lung. Therefore, treating with rintatolimod helped mitigate lung fibrosis. Moreover, treatment with rintatolimod significantly upregulated the expression of various molecules that mediate the adhesion of immune cells to blood vessels like VCAM1 and TGFβ2 and many other integrin genes that are associated with increased blood vessel formation [123] [124] .

Ovarian cancer

Treatment with rintatolimod, in combination with interferon alpha-2b (IFN), and oral celecoxib, was efficacious, in patients (n=25) with advanced recurrent ovarian cancer, in a phase I/II trial. Median PFS was 8.4 (3-16.4) months. Median overall survival was 30 (8-66) months. Overall response rate was 55.6% and the disease control rate (DCR) was 77.8%, consistent with the expected platinum-sensitive response. Among responders, median duration of response was 11.7 (6-16.4) months. Rintatolimod showed important role as a TLR3 agonist, acting synergistically with high-dose IFNa and celecoxib to selectively enhance Teff cell-attractants while suppressing Treg-attractants in the tumour microenvironment with a concomitant increase in the Teff/Treg ratio. The study showed that similar findings were seen combining rintatolimod with chemokine-targeting and chemo-immunotherapy in patients being treated for recurrent ovarian cancer. The importance of boosting the Teff/Treg ratio in the tumor microenvironment is that it is associated with the conversion of ‘cold’ tumors into ‘hot’ tumours, which have an increased sensitivity to chemo-immunotherapy and an improved chance of showing tumour regression [213] [216] .

In a phase I/II trial, treatment with rintatolimod (IP, 200mg) in combination with cisplatin (IP, 50 mg/m2) and pembrolizumab (IV, 200mg) in patients (n = 17) with recurrent, platinum sensitive ovarian cancer was effective. Observed clinical responses were 2 complete responses (15.4%), 3 partial responses (23.1%), 3 stable disease (23.1%), 5 progressions (38.4%) for a clinical benefit rate (CR+PR+SD) of 61.6%. From 13 patients, 77 IP wash samples were collected at serial time points. MSD measurements in IP washes revealed an acute increase in granzyme B, perforin, TNF alpha, CXCL9, CXCL10, CXCL11 after treatment (p < 0.05). Longitudinal data revealed a progressive increase in some biomarkers in the locoregional environment; CXCL9, CXCL10, CXCL11, perforin and TNF alpha were all increased from baseline levels at cycle 1 to baseline of cycle 6 (p<0.05). CXCL12 was also increased acutely after treatment (p < 0.05) [212] [211] .

In a phase IIa trial of rintatolimod in patients with colorectal cancer, the study's primary endpoint was met, evidenced by increased CD8a expression post-treatment (p=0.046). Saw increase in the CD8a/CD4 (p=0.03), CD8a/FOXP3 (p<0.01) and GZMB/FOXP3 (p<0.01) ratios. The expression of CTL-attracting chemokines CCL5 (p=0.08), CXCL9 (p=0.05), and CXCL10 (p=0.06) were increased, while expression of the Treg/MDSC attractant CXCL12 (p=0.07) was decreased post-treatment. Median OS was 10.5 (90% CI 2.2-15.2) months, and the median PFS was 1.5 (90% CI 1.4, 1.8) months [176] [175] .

In phase I study of chemokine modulation therapy (CKM) including rintatolimod with pembrolizumab in breast cancer patients (n=6), the pre-determined primary endpoint of efficacy was met (increase in CD8⍺ in TME). Uniform increase of immune markers upon treatment was observed: CD8⍺ mRNA (6.1-fold; p-0.034), GZMB mRNA (3.5-fold; p=0.058), ratios of CD8⍺/FOXP3 and GZMB/FOXP3 (5.7-fold; p=0.036, and 7.6-fold; p=0.024 respectively), thus successfully meeting the pre-determined primary endpoint in the study (increase in CD8⍺ in TME). In addition, an increase in CTL attractants CXCL10 (2.6-fold; p=0.104) and CCL5 (3.3-fold; p=0.019) was observed. In contrast, Treg marker FOXP3 or Treg attractants CCL22 or CXCL12 were not enhanced. Three patients had stable disease lasting 2.4, 2.5 and 3.8 months, as of data cut off September 1, 2021. An additional patient (non-evaluable) had a partial response (breast tumor autoamputation) with massive tumor necrosis in the post-CKM biopsy [171] [169] .

Breast cancer

Phase I

: In a phase I trial, treatment with rintatolimod in triple negative breast cancer (TNBC) patients showed promising clinical activity with a pathologic complete response (pCR) of 56% (5/9 patients) and microinvasive residual breast cancer (ypTmic) rate of 66%, comparable to pembrolizumab combination with neoadjuvant chemotherapy (NAC) [160] [164] [161] .

Chronic fatigue syndrome (CFS)/Myalgic encephalomyelitis (ME)

Relatively more XMRV antibody-positive patients had a >25% increase in exercise tolerance testing (ETT) after treatment with rintatolimod, compared with placebo, than the XMRV antibody-negative patients, in a phase III trial of the drug in patients with CFS. In this placebo-controlled, double-blind trial, patients (n = 208) were randomised to receive rintatolimod 200-400mg or an equivalent volumen of placebo twice-weekly, via IV-infusion, for 40 weeks. Baseline serum samples from all patients were analysed for antibodies directed against XMRV. Results also suggest that the XMRV antibody-negative patients with CFS had a lower activity level and a reduced ability to complete normal daily activities at baseline [243] .

In a a AMP-511 expanded access programme (EAP) that evaluated the safety of rintatolimod in patients with severely debilitating chronic fatigue syndrome, data of post-COVID patients with new onset ME/CFS showed a decrease in fatigue compared to baseline was statistically significant (p<0.003), despite the small number of patients (n=4) following at least 12 weeks of rintatolimod treatment [74] [63]

Rintatolimod increased oxygen consumption in parallel with improvements in treadmill performance in patients with CFS in a phase III study. Maximal oxygen consumption (VO2 max) increased 10-fold with rintatolimod compared with placebo, and there was a significant correlation between improvement in exercise duration and increase in VO2 max [247] .

Rintatolimod significantly improved patients physical performance as assessed by Treadmill Exercise Tolerance Testing (ETT) in a 40-week placebo-controlled phase III study in 234 patients with severely debilitating CFS. Rintatolimod 400mg twice-weekly was superior to placebo for improved ETT (19.4 vs 5.1%) for the patient population that completed 40 weeks' treatment and also for the intent-to-treat population (17.7 vs 4.3%) that completed <40 weeks treatment. In intent to treat analysis, rintatolimod 40mg for 40 weeks improved intra-patient placebo adjusted ET 21.3% from baseline. Correction in patients with reduced dosing resulted in increased placebo improvement to 28% (p = 0.022). The proportion of patients with exercise improvements of at least 25% and 50% were 1.7 and 1.9-fold greater, respectively, with rintatolimod versus placebo (p < 0.05). An improvement of exercise tolerance of greater or equal to 25% from baseline (16% placebo-adjusted improvement; p=0.013) was demonstrated in a significantly greater percentage of rintatolimod patients (39%) vs. placebo patients (23%). In addition, rintatolimod also reduced dependence on CFS medications compared with placebo (p < 0.05) [62] [88] [49] [76] [249] . A retrospective analysis of data from the trial showed that, for a subset of patients with baseline exercise tolerance (ET) of >9mins, 33% of patients on rintatolimod improved ET duration by ≥25% versus 12% of patients on placebo (p=0.004). Additionally, 23% of patients on rintatolimod improved by ≥50% in ET duration, compared with 4.5% of patients in placebo (p=0.003). Similar clinically significant improvements for the cohort of study subjects with baseline ET >9mins, as a function of the same ET parameters, were also noted for the Karnofsky Performance Score (KPS) and Vitality (SF-36 subscale) quality of life secondary endpoint. Rintatolimod reduced deterioration in ET compared with placebo in patients who failed to physically improve [77] . In another retrospective analysis of the AMP 516, segmented primarily by disease duration, demonstrated that at least 25% improvement in placebo-adjusted exercise tolerance was observed in 51% of rintatolimod treated patients in a cohort with a disease duration of two to eight years vs. 18% of placebo patients (33% placebo-adjusted improvement, p=0.003). Also, patient subset with less than two years or greater than eight years of disease duration failed to show a clinically-significant response [62] [75] .

Rintatolimod significantly improved cognitive and physical performance in a Belgium clinical study. Physical performance for activities of daily living, measured using the Karnofsky Performance Score, showed an improvement of 43% (from 53 at baseline to 76). Exercise performance was measured by bicycle testing; oxygen uptake improved from 1.16 L/min at baseline to 1.48 L/min after treatment with rintatolimod. The cognitive improvement seen in patients receiving rintatolimod was measured using the cognitive subscale of the SCL 90-R or neuropsychological function tests. Significantly greater improvements were seen in patients receiving rintatolimod compared with placebo. Of patients treated with rintatolimod, about 80% experienced an apparent 'complete clinical recovery' after 6 months' treatment; spontaneous improvement in untreated patients with CFS is about 2%. Patients with CFS were randomised to receive rintatolimod (200-400mg twice-weekly) or placebo for 24 weeks [267] [263] [268] .

The effects of rintatolimod on immune function were compared with those of placebo in a randomised, double-blind, crossover study (ACTG 056) in volunteers. Overall, there were no significant differences between the two treatments in terms of production of interferon and biological markers of interferon, T lymphocytic function, lymphocyte proliferative responses and natural killer cell activity. Symptom scores were greater in rintatolimod recipients than in placebo recipients but symptoms were mild in nature and the between-group difference was only significant on the day after dosing [260] .

In 15 patients with chronic fatigue syndrome, rintatolimod normalised the upregulated 2-5A synthetase/RNase L system and cleared human herpesvirus 6 antigen-positive cells from peripheral blood mononuclear cell cultures [264] .

Pharmacoeconomics

The potential pharmacoeconomic impact of rintatolimod on the treatment of CFS/ME has been investigated. Pharmacoeconomic data, including medication use, and cost and charges of hospitalisation and emergency room visits, were retrospectively collected. Mean annual health-care charges for patients receiving rintatolimod were calculated to be $US2 097, compared with $US8 606 for placebo recipients [255] .

Hepatitis B

Results of a phase I/II study of rintatolimod 400-600mg two to three times/week in eight patients with chronic hepatitis B indicated that the drug may have an antiviral effect. Four patients lost HBV DNA and three patients became HBeAg seronegative during 24 weeks' treatment. None of the patients have relapsed [269] .

HIV infections

The effects of rintatolimod alone or in combination with zidovudine, were investigated in a placebo-controlled study in HIV seropositive patients. Continuous therapy with rintatolimod for at least 2 years prevented the progression of HIV infection in p24 seronegative patients. When administered in combination with zidovudine, CD4+ cell counts were increased compared to those observed in patients receiving each agent alone. Rintatolimod also appeared to restore immune function in HIV-infected patients, as shown by the return or increase in delayed-type hypersensitivity [261] .

Results from a phase I study (ACTG 038) were unable to confirm previous beneficial effects of rintatolimod in HIV infection. A total of 39 HIV-infected patients with asymptomatic disease or early ARC received one to six doses of rintatolimod for 9 or 25 weeks. Rintatolimod had no significant effects on p24 antigenaemia, HIV viraemia or the number of HIV-infected cells. However, the rate of CD4+ cell depletion was reduced; this effect was dose-dependent [270] .

In a study conducted in 36 zidovudine-treated patients, rintatolimod therapy was most effective when initiated earlier in the course of HIV disease. Over a 48-week study period, patients treated with rintatolimod (400 or 700mg twice-weekly) had a mean decrease in CD4+ count of 52 cells/µl compared with 89 cells/µl in placebo recipients. Rintatolimod-treated patients with baseline CD4+ counts ≥300 cells/µl showed a mean increase in CD4+ count of 26 cells/µl which peaked at week 24. Placebo recipients had a consistent decrease from baseline. A change to rintatolimod therapy after 48 weeks of placebo treatment reversed the CD4+ decline in seven patients. Rintatolimod recipients were less likely to progress to AIDS than placebo recipients [257] .

Significantly fewer patients relapsed within the first 30 days of structured treatment interruption (STI) when treated with rintatolimod. In this phase IIb study, the primary endpoint was the mean total time of HAART-free intervals before rebound of plasma HIV-1 RNA. There were two groups of patients: the "Harvard cohort" of eight newly/acutely HIV-infected patients and the "study group", designed to be similar to the referenced Harvard cohort. The similarities being a) HAART was given for ≥9 months; b) CD4 ≥400 cells/mL and c) HIV RNA levels below 50 copies/mL. The main difference between the groups was that the Harvard cohort were studied within weeks or months of initial infection whereas the study group had been infected with HIV for several years. Interim data analysis were performed with a control (non-rintatolimod treated) group obtained from scientific literature "meta-analysis" and a second with a concurrent control (non-rintatolimod treated) group obtained from identical, participating medical institutions. In the meta-analysis, none of the patients relapsed while on rintatolimod within the first 30 days compared with 86% of a control group of patients (p = 0.012). In the second analysis, the median duration of STI in the rintatolimod group was >18 weeks, compared with 7 weeks in the concurrent control, non-rintatolimod group [253] .

In a phase IIb study (AMP 720) of patients with HIV undergoing up to three structured treatment interruptions (STI) of HAART, rintatolimod (400mg IV twice-weekly) therapy resulted in significant prolongation of controlled HIV viraemia, compared with untreated controls. Patients taken off HAART but given rintatolimod (n = 7) continued to show virus levels <5000 copies/mL for a mean of 25 weeks and counting. In the control group, patients (n = 9) taken off HAART and not given rintatolimod, developed an HIV rebound within a mean of 13 weeks. In addition, the rintatolimod group demonstrated an increase in CD8+ cells suggesting induction of immunogenicity [250] [251] [252] .

Results from a phase II trial of rintatolimod demonstrated that the reduction in that measure did not show a significant difference at the 13-week time point. However, initial analysis revealed that subjects in the Ampligen group ha experienced lower levels of fatigue at multiple time points during the treatment phase than the placebo group. The Six-Minute Walk Test also revealed a higher impact of Ampligen on distance traveled in six minutes at Week 13 than placebo [96] [91] .

Future Events

Expected Date Event Type Description Updated
31 Dec 2023 Trial Update AIM ImmunoTech in collaboration with Erasmus MC and AstraZeneca plans a phase Ib/II DURIPANC trial in Pancreatic cancer (Combination therapy, Metastatic disease) in Netherlands (IV) before the end of 2023 (700360601) [237] 12 Jan 2024
30 Sep 2023 Trial Update AIM ImmunoTech plans a phase II trial in Pancreatic cancer (Late-stage disease) (Unspecified route), in Q3 2023 [225] 18 Aug 2023
30 Jun 2023 Trial Update AIM ImmunoTech plans a phase II trial in Post-acute COVID-19 syndrome (In adults) in Q2 2023 (IV) (NCT05592418) (700342445) [238] 10 Jul 2023
31 Dec 2022 Trial Update AIM ImmunoTech, University of Nebraska Medical Center and Erasmus MC plan a phase II trial in Pancreatic cancer (Late-stage disease, Combination therapy) in Netherlands, Europe and USA in Q3 2022 [239] 18 Jul 2022
30 Sep 2022 Trial Update AIM ImmunoTech in collaboration with Amarex Clinical Research plans a phase II trial in Pancreatic cancer (Late-stage disease, Combination-therapy) in September 2022 (NCT05494697) (700355490) 13 Aug 2022
30 Apr 2022 Trial Update Roswell Park Cancer Institute plans a phase II trial for Malignant melanoma (Combination therapy, Second-line therapy or greater) in USA (Intradermal) (NCT04093323) (700311594) 05 Apr 2022
31 Dec 2021 Trial Update Hemispherx Biopharma plans a clinical trial for Breast cancer (Late-stage disease, Metastatic disease) in 2021 (9306834) [166] 29 Nov 2021
18 Oct 2021 Regulatory Status AIM Immuno Tech plans to file IND application for initiation of phase II trials for Pancreatic cancer [186] 29 Nov 2021
18 Oct 2021 Regulatory Status AIM Immuno Tech plans to file Fast Track Designation with the US FDA for Pancreatic cancer by October 2021 [186] 29 Nov 2021
08 Mar 2021 Trial Update AIM ImmunoTech in collaboration with Centre for Human Drug Research plans a AMP-COV-100 (CHDR2049) trial in COVID-2019 infections (Intranasal) in the first quarter of 2021 (9314559) (700333332) [110] 10 Mar 2021
31 Dec 2020 Trial Update Hemispherx Biopharma plans a clinical trial for Pancreatic cancer (Combination therapy) in Netherlands in 2019 [166] 03 Jan 2020
09 Aug 2020 Trial Update AIM ImmunoTech and Roswell Park Cancer Institute plans a phase I/IIb trial for COVID-2019 infections in cancer patients (Combination therapy) in USA (IV) in August 2020 (NCT04379518) (700321604) [11] 18 Sep 2020
31 Dec 2019 Trial Update Hemispherx Biopharma plans additional clinical trials for Cancer in 2019 [241] 19 Dec 2018
31 Dec 2019 Trial Update Hemispherx Biopharma and Roswell Park Cancer Institute plan a phase II trial for Colorectal cancer (Combination therapy, Late-stage disease; Metastatic disease, Second-line therapy or greater) in USA in 2019 [193] 19 Aug 2019
31 Dec 2019 Trial Update Hemispherx Biopharma and Roswell Park Cancer Institute plan a phase II trial for Bladder cancer, Melanoma and Renal cell carcinoma (Combination therapy, Late-stage disease, Second-line therapy or greater) in USA in 2019 [193] 15 Mar 2019
31 Dec 2019 Trial Update Hemispherx Biopharma and University of Nebraska Medical Center plan a clinical trial for Non-small cell lung cancer (First-line therapy, Combination therapy) in USA in 2019 [193] 15 Mar 2019
31 Dec 2019 Trial Update Hemispherx Biopharma and Roswell Park Cancer Institute plan a clinical trial for Breast cancer (Inoperable/unresectable, Combination therapy, Metastatic disease, Second line therapy or greater) in USA in 2019 [193] 09 Apr 2019
31 Dec 2019 Trial Update Hemispherx Biopharma and Buffett Cancer Center plan a clinical trial for Non-small cell lung cancer in 2019 (9257508) 18 Mar 2022
07 Dec 2019 Trial Update Hemispherx Biopharma plans a phase I trial for Breast cancer (Combination therapy, Early-stage disease) in USA by 2020 [166] 15 Oct 2019
30 Sep 2019 Trial Update Roswell Park Cancer Institute and National Cancer Institute plan a phase Ib/II trial in Breast cancer (Neoadjuvant therapy, First-line therapy, Combination therapy) in USA (IV), in September 2019 (700311275), (NCT04081389) 23 Aug 2021
30 Jun 2019 Trial Update Hemispherx Biopharma, Roswell Park Cancer Institute, and National Cancer Institute plan a phase II trial in Prostate cancer (Neoadjuvant therapy) in USA in June 2019 (NCT03899987) (700306120) [240] 09 Dec 2019
11 Feb 2019 Trial Update Hemispherx Biopharma plans a phase I/II trial for Ovarian Cancer (Combination therapy, Recurrent, Second-line therapy or greater) in USA (700302125), (NCT03734692) [241] 13 Feb 2019
31 Dec 2018 Regulatory Status Hemispherx Biopharma announces intention to submit applications for Early Access Programs (EAP) in Europe and additional countries in 2018 [242] 05 Mar 2018
31 Dec 2018 Regulatory Status Hemispherx Biopharma intends to initiate a Special Access Program (SAP) for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Canada in May 2018 [17] 29 Oct 2018
31 May 2018 Regulatory Status Hemispherx Biopharma plans to supply Ampligen® for pancreatic cancer patients in Canada under a Special Access Program (SAP) in May 2018 [191] 20 Jun 2018
01 Feb 2018 Trial Update Roswell Park Cancer Institute and National Cancer Institute plan a early phase IIa trial for Colorectal cancer (Metastatic disease, Combination therapy) in USA in February 2018 (NCT03403634) (700292415) 25 Jul 2018

Development History

Event Date Update Type Comment
25 Mar 2024 Scientific Update Interim pharmacodynamics data from an expanded access program in Pancreatic cancer released by AIM ImmunoTech [198] Updated 28 Mar 2024
08 Feb 2024 Scientific Update Efficacy and adverse events data from a phase II trial in Post-acute-COVID-19-syndrome released by AIM ImmunoTech [96] Updated 14 Feb 2024
25 Jan 2024 Trial Update Hemispherx Biopharma in collaboration with National Cancer Institute and Roswell Park Comprehensive Cancer Center reinitiates a phase II trial in Prostate cancer (Combination therapy, Late-stage disease, Neoadjuvant therapy) in USA (IV) in January 2024 (NCT03899987) Updated 26 Mar 2024
25 Jan 2024 Scientific Update Interim pharmacodynamics and safety data from a phase II trial in Prostate cancer presented at the 2024 Genitourinary Cancers Symposium (ASCO-GeCS-2024) [202] Updated 18 Mar 2024
24 Jan 2024 Regulatory Status AIM ImmunoTech receives authorization from the Erasmus Medical Center Ethics Committee to open a European site for the ongoing phase II trial (AMP-270) of Ampligen [183] Updated 31 Jan 2024
09 Jan 2024 Phase Change - I/II Phase-I/II clinical trials in Pancreatic cancer (Combination therapy, Late-stage disease, Metastatic disease) in Netherlands (IV) (NCT05927142) [200] Updated 12 Mar 2024
30 Nov 2023 Trial Update AIM ImmunoTech completes a phase II trial for Post-acute-COVID-19-syndrome in USA (IV) (NCT05592418) Updated 01 Feb 2024
27 Nov 2023 Patent Information AIM ImmunoTech receives two world wide patent protections for Ampligen® for the treatment of Chronic fatigue syndrome [224] Updated 29 Nov 2023
17 Oct 2023 Licensing Status Rintatolimod - AIM ImmunoTech is available for licensing as of 17 Oct 2023 [2] Updated 19 Oct 2023
11 Sep 2023 Scientific Update Updated efficacy data from a phase I trial in Triple negative breast cancer released by AIM ImmunoTech [160] Updated 13 Sep 2023
11 Sep 2023 Trial Update AIM ImmunoTech plans a phase II trial for Triple-negative breast cancer (Combination therapy, Early-stage disease, Neoadjuvant therapy) [160] Updated 13 Sep 2023
15 Aug 2023 Patent Information AIM ImmunoTech has patent protection for rintatolimod in South Africa, prior to August 2023 [225] Updated 18 Aug 2023
15 Aug 2023 Trial Update AIM ImmunoTech plans a phase II trial in Pancreatic cancer (Late-stage disease) (Unspecified route), in Q3 2023 [225] Updated 18 Aug 2023
08 Aug 2023 Trial Update AIM ImmunoTech completes enrolment in its phase II trial for Post-acute-COVID-19-syndrome in USA (IV) (NCT05592418) [94] Updated 10 Aug 2023
29 Jun 2023 Phase Change - II Phase-II clinical trials in Post-acute-COVID-19-syndrome in USA (IV) (NCT05592418) Updated 10 Jul 2023
27 Jun 2023 Trial Update AIM ImmunoTech in collaboration with Erasmus MC and AstraZeneca plans a phase Ib/II DURIPANC trial in Pancreatic cancer (Combination therapy, Metastatic disease) in Netherlands (IV) before the end of 2023 [237] Updated 12 Jan 2024
04 Apr 2023 Regulatory Status AIM ImmunoTech receives IRB approval for phase II trial protocol in COVID-19 infections [79] Updated 06 Apr 2023
03 Apr 2023 Trial Update AIM ImmunoTech plans a phase II trial in Post-acute COVID-19 syndrome (In adults) in Q2 2023 (IV) (NCT05592418) [238] Updated 10 Jul 2023
16 Mar 2023 Scientific Update Pharmacodynamics data from a preclinical studies in Ebola virus infections released by AIM ImmunoTech [140] Updated 20 Mar 2023
08 Mar 2023 Regulatory Status AIM ImmunoTech intends to file an IND application for Ebola virus infection [128] Updated 13 Mar 2023
06 Mar 2023 Trial Update Roswell Park Cancer Institute and AIM ImmunoTech suspended a phase-I/II trial in COVID-2019 infections (Combination therapy) in USA (IV) for revision of trial protocol (NCT04379518) Updated 15 Mar 2023
27 Feb 2023 Trial Update Roswell Park Cancer Institute completes a phase I trial in Breast cancer (Combination therapy, Early-stage disease, Neoadjuvant therapy) in USA (IV) (NCT04081389) Updated 16 Jun 2023
27 Feb 2023 Phase Change - II Phase-II clinical trials in Pancreatic cancer (Late-stage disease, Inoperable/Unresectable, Second-line therapy or greater) in USA (IV) (NCT05494697) Updated 09 Mar 2023
06 Feb 2023 Trial Update Hemispherx Biopharma in collaboration with National Cancer Institute and Roswell Park Comprehensive Cancer Center terminates a phase II trial in Prostate cancer (Combination therapy, Late-stage disease, Neoadjuvant therapy) in USA (IV) due to drug supply issue (NCT03899987) Updated 15 Feb 2023
17 Jan 2023 Licensing Status AIM ImmunoTech enters into an agreement with Erasmus MC and AstraZeneca for a DURIPANC Study in Adenocarcinoma (Combination therapy, Metastatic disease) [5] Updated 23 Jan 2023
17 Jan 2023 Trial Update AIM ImmunoTech in collaboration with Erasmus MC and AstraZeneca plans a clinical DURIPANC Study in Adenocarcinoma (Combination therapy, Metastatic disease) [5] Updated 23 Jan 2023
09 Jan 2023 Patent Information AIM ImmunoTech has patent protection for rintatolimod in the Netherlands [226] Updated 12 Jan 2023
08 Dec 2022 Scientific Update Safety and pharmacodynamics data from a phase I trial in Healthy subjects released by AIM ImmunoTech [115] Updated 12 Dec 2022
06 Dec 2022 Scientific Update Efficacy, pharmacodynamics and adverse events data from a phase I trial in Triple negative breast cancer presented at the 45th Annual San Antonio Breast Cancer Symposium (SABCS-2022) [164] Updated 14 Feb 2023
14 Nov 2022 Scientific Update Adverse events data from a phase I trial in Breast cancer released by Aimmune Therapeutics [163] Updated 21 Nov 2022
07 Nov 2022 Phase Change - II Phase-II clinical trials in Triple-negative-breast-cancer (Second-line therapy or greater, Metastatic disease, Inoperable/Unresectable, Late-stage disease, Combination therapy) in USA (IV) (AIM ImmunoTech pipeline; November 2022) [129] Updated 07 Nov 2022
02 Nov 2022 Regulatory Status Rintatolimod - AIM ImmunoTech receives Orphan Drug status for Ebola virus infections in USA [129] Updated 04 Nov 2022
31 Oct 2022 Active Status Review Rintatolimod is still in phase I trials for Pancreatic cancer in Netherlands Updated 02 Nov 2022
12 Oct 2022 Phase Change - Preclinical Preclinical trials in Post-acute-COVID-19-syndrome in USA (unspecified route) [92] Updated 14 Oct 2022
21 Sep 2022 Active Status Review Rintatolimod is still in phase I trials for Triple-negative-breast cancer in USA (NCT03599453) Updated 21 Sep 2022
22 Aug 2022 Phase Change - II Phase-II clinical trials in Malignant melanoma (Combination therapy, Second-line therapy or greater) in USA (IV) (NCT04093323) [81] Updated 04 Sep 2022
18 Aug 2022 Phase Change - II Phase-II clinical trials in Pancreatic cancer (Late-stage disease, Second-line therapy or greater) in USA, Europe (IV) (NCT05494697) [182] Updated 23 Aug 2022
18 Aug 2022 Regulatory Status AIm ImmunoTech receives Institutional Review Board approval for the phase II trial protocol for rintatolimod in Pancreatic cancer prior to August 2022 [182] Updated 23 Aug 2022
13 Aug 2022 Trial Update AIM ImmunoTech in collaboration with Amarex Clinical Research plans a phase II trial in Pancreatic cancer (Late-stage disease, Combination-therapy) in September 2022 (NCT05494697) Updated 13 Aug 2022
28 Jun 2022 Phase Change - No development reported No recent reports of development identified for phase-I development in Pancreatic-cancer(Late-stage disease) in Netherlands (IV) Updated 28 Jun 2022
28 Jun 2022 Phase Change - No development reported No recent reports of development identified for phase-I development in Triple-negative-breast-cancer(Combination therapy, Inoperable/Unresectable, Metastatic disease, Second-line therapy or greater) in USA (IV) Updated 28 Jun 2022
13 Jun 2022 Patent Information AIM ImmunoTech has patent protection for rintatolimod in the Netherlands [227] Updated 16 Jun 2022
24 May 2022 Regulatory Status AIM ImmunoTech plans to file an Investigation New Drug (IND) application in Chronic Fatigue Syndrome associated with COVID-2019 infections [74] Updated 24 May 2022
18 May 2022 Scientific Update Efficacy and adverse events data from an expanded-access programme in Chronic Fatigue Syndrome associated with COVID-2019 infections released by AIM Immunotech [74] Updated 24 May 2022
16 May 2022 Trial Update AIM ImmunoTech, University of Nebraska Medical Center and Erasmus MC plan a phase II trial in Pancreatic cancer (Late-stage disease, Combination therapy) in Netherlands, Europe and USA in Q3 2022 [239] Updated 18 Jul 2022
16 May 2022 Trial Update AIM ImmunoTech plans a phase-II trial for Ovarian cancer (Second-line therapy, Late-stage disease, Recurrent) in USA [239] Updated 20 May 2022
14 Apr 2022 Scientific Update Efficacy and adverse events data from a phase I trial in Breast cancer released by AIM ImmunoTech [171] Updated 14 Apr 2022
11 Apr 2022 Scientific Update Efficacy and adverse events data from a phase IIa trial in Colorectal cancer released by AIM ImmunoTech [176] Updated 13 Apr 2022
04 Apr 2022 Trial Update Roswell Park Cancer Institute plans a phase II trial for Malignant melanoma (Combination therapy, Second-line therapy or greater) in USA (Intradermal) (NCT04093323) Updated 05 Apr 2022
31 Mar 2022 Licensing Status AIM ImmunoTech terminates agreement with hVIVO to test rintatolimod (Ampligen) in a phase IIa Human Challenge Trial as a potential intranasal antiviral propylactic therapy [8] Updated 27 Apr 2023
31 Mar 2022 Trial Update AIM ImmunoTech completes enrolment in a phase I trial in Breast cancer (Combination therapy, Metastatic disease, Second-line therapy or greater, Inoperable/Unresectable) in USA (IV) [165] (NCT03599453) Updated 05 Apr 2022
28 Mar 2022 Scientific Update Pharmacodynamics data from preclinical trial in Pancreatic cancer released by AIM ImmunoTech [201] Updated 30 Mar 2022
16 Mar 2022 Regulatory Status The US FDA lifts clinical hold on IND for pancreatic cancer [185] Updated 18 Mar 2022
09 Mar 2022 Scientific Update Efficacy data from a phase I/II trial in Ovarian Cancer (Combination therapy, Recurrent, Second-line therapy or greater) released by AIM ImmunoTech [212] Updated 14 Mar 2022
08 Mar 2022 Scientific Update Efficacy and pharmacodynamics data from the Erasmus MC early access programme in Pancreatic cancer released by AIM ImmunoTech [197] Updated 15 Mar 2022
24 Jan 2022 Trial Update Roswell Park Cancer Institute withdraws a phase IIa trial prior enrolment for Colorectal cancer (Combination therapy, Inoperable/unresectable, Late-stage disease, Metastatic disease, Second-line therapy or greater) in USA due to trial implementation issues (IV) (NCT04119830) Updated 18 Feb 2022
24 Jan 2022 Scientific Update Efficacy and adverse events data from a phase I/II trial in Ovarian cancer released by AIM ImmunoTech [213] Updated 27 Jan 2022
16 Nov 2021 Regulatory Status AIM ImmunoTech announces intention to submit NDA to the US FDA Pancreatic cancer (Late-stage disease, Metastatic disease) [72] Updated 29 Nov 2021
16 Nov 2021 Trial Update AIM ImmunoTech and the University of Pittsburgh plans a phase II trial for Ovarian cancer (Late-stage disease, Metastatic disease, Recurrent, Second-line therapy or greater) [72] Updated 29 Nov 2021
01 Nov 2021 Regulatory Status The US FDA places clinical hold on IND for pancreatic cancer [9] Updated 06 Apr 2022
19 Oct 2021 Regulatory Status AIM ImmunoTech files an IND application with the US FDA for rintatolimod in Pancreatic cancer [180] Updated 21 Oct 2021
19 Oct 2021 Regulatory Status AIM ImmunoTech submits Fast Track status application for rintatolimod in Pancreatic cancer (Late-stage disease, Metastatic disease, Adjunctive treatment) to US FDA [180] Updated 21 Oct 2021
19 Oct 2021 Scientific Update Efficacy data from the Erasmus MC early access programme in Pancreatic cancer released by AIM ImmunoTech [180] Updated 21 Oct 2021
19 Oct 2021 Trial Update AIM ImmunoTech plans the AMP-270 phase II trial in pancreatic cancer (Late-stage disease, Metastatic disease, Adjunctive treatment) in USA and Netherlands [180] Updated 21 Oct 2021
04 Oct 2021 Regulatory Status AIM Immuno Tech plans to file Fast Track Designation with the US FDA for Pancreatic cancer by October 2021 [186] Updated 29 Nov 2021
04 Oct 2021 Regulatory Status AIM Immuno Tech plans to file IND application for initiation of phase II trials for Pancreatic cancer [186] Updated 29 Nov 2021
04 Oct 2021 Regulatory Status AIM ImmunoTech plans to get approval for rintatolimod for Pancreatic cancer from the USFDA [186] Updated 06 Oct 2021
04 Oct 2021 Trial Update AIM Immuno tech plans phase II trial for Pancreatic cancer (Metastatic disease, Monotherapy, Combination therapy) (IV) in Netherlands and other countries [186] Updated 06 Oct 2021
04 Oct 2021 Trial Update AIM Immuno Tech plans phase III trials for Pancreatic cancer [186] Updated 06 Oct 2021
29 Sep 2021 Trial Update AIM ImmunoTech plans a phase II trials for COVID-2019 infections (Intravenous Infusion) [97] Updated 29 Sep 2021
28 Sep 2021 Regulatory Status AIM ImmunoTech submits a Pre-Investigational New Drug application (Pre-IND) to the US FDA for two phase II trials for COVID-2019 infections [97] Updated 29 Sep 2021
28 Sep 2021 Trial Update AIM ImmunoTech plans a phase II trials for COVID-2019 infections (Intranasal) [97] Updated 29 Sep 2021
27 Sep 2021 Patent Information AIM ImmunoTech files for patent protection for intranasal therapy of rintatolimod for the treatment of respiratory infections [228] Updated 29 Sep 2021
14 Sep 2021 Biomarker Update Biomarkers information updated Updated 17 Sep 2021
08 Sep 2021 Regulatory Status AIM ImmunoTech submits Pre-Investigational New Drug application (Pre-IND) to US FDA for post-COVID-19 cognitive dysfunction [100] Updated 13 Sep 2021
08 Sep 2021 Trial Update AIM ImmunoTech plans a phase II trial for post-COVID-19 cognitive dysfunction [100] Updated 13 Sep 2021
25 Aug 2021 Patent Information AIM ImmunoTech has pending patents for the use of rintatolimod both as intranasal and intravenous therapy for COVID-19 cognitive dysfunction [229] Updated 30 Aug 2021
17 Aug 2021 Trial Update AIM ImmunoTech plans a phase II/III trial for Pancreatic cancer in Europe and USA (IV) [187] Updated 23 Aug 2021
13 Jul 2021 Licensing Status AIM ImmunoTech has signed a contract with hVIVO to test rintatolimod (Ampligen) in a phase IIa Human Challenge Trial as a potential intranasal antiviral propylactic therapy [6] Updated 13 Jul 2021
21 Jun 2021 Trial Update AIM ImmunoTech in collaboration with Centre for Human Drug Research (CHDR) completes enrolment in the phase I AMP-COV-100 trial in COVID-19 infections (In volunteers) in Netherlands [108] Updated 28 Jun 2021
21 Jun 2021 Trial Update AIM ImmunoTech plans a phase II trial for COVID-2019 infections(Prevention) [108] Updated 28 Jun 2021
21 Jun 2021 Phase Change - Marketed Launched for Chronic fatigue syndrome in USA (IV) Updated 21 Jun 2021
21 Jun 2021 Phase Change - Marketed Launched for HIV infections in USA (IV) Updated 21 Jun 2021
21 Jun 2021 Phase Change - Marketed Launched for Malignant melanoma in USA (IV) Updated 21 Jun 2021
21 Jun 2021 Phase Change - Marketed Launched for Renal cell carcinoma in USA (IV) Updated 21 Jun 2021
14 Jun 2021 Patent Information AIM ImmunoTech has patent protection for rintatolimod in Netherlands [230] [239] Updated 20 May 2022
14 Jun 2021 Scientific Update Pharmacodynamic data from a preclinical trial in COVID-2019 infections reelased by AIM Immuno Tech [123] [124] Updated 21 Jun 2021
27 May 2021 Trial Update AIM ImmunoTech plans a phase I/II trial for COVID-2019 infections (Inhalation) [99] Updated 01 Jun 2021
27 Apr 2021 Scientific Update Updated adverse events data from the phase I AMP-COV-100 trial in COVID-2019 infections released by AIM ImmunoTech [112] Updated 30 Apr 2021
07 Apr 2021 Scientific Update Adverse events data from the phase I AMP-COV-100 trial in COVID-2019 infections released by AIM ImmunoTech [111] Updated 14 Apr 2021
07 Apr 2021 Trial Update AIM ImmunoTech plans a phase II trial for COVID-2019 infections [111] Updated 14 Apr 2021
01 Apr 2021 Licensing Status AIM ImmunoTech enters into material transfer and research agreement with University of Cagliari for the research and development of the effects of rintatolimod [9] Updated 06 Apr 2022
31 Mar 2021 Scientific Update Pharmacodynamics data from a preclinical study in COVID-2019 infections released by AIM ImmunoTech [121] Updated 29 May 2021
30 Mar 2021 Trial Update Roswell Park Cancer Institute plans a phase II trial for Malignant melanoma (Combination therapy, Second-line therapy or greater) in USA (Intradermal) (NCT04093323) Updated 23 Apr 2021
08 Mar 2021 Phase Change - I Phase-I clinical trials in COVID-2019 infections (In volunteers) in Netherlands (Intranasal) [109] Updated 10 Mar 2021
08 Mar 2021 Phase Change - I Phase-I clinical trials in COVID-2019 infections (Prevention) in Netherlands (Intranasal) [109] Updated 10 Mar 2021
24 Feb 2021 Regulatory Status Rintatolimod receives Orphan Drug status for Pancreatic cancer in European Union [178] Updated 26 Feb 2021
24 Feb 2021 Trial Update AIM ImmunoTech plans a phase I trial in Pancreatic cancer (Combination therapy) in the Netherlands [178] Updated 26 Feb 2021
24 Feb 2021 Trial Update AIM ImmunoTech plans a phase II/III follow-up trial in Pancreatic cancer in the Netherlands and in the US [178] Updated 26 Feb 2021
24 Feb 2021 Trial Update Updated efficacy data from a early access programme for Rintatolimod in Pancreatic cancer released by AIM ImmunoTech [178] Updated 26 Feb 2021
23 Feb 2021 Regulatory Status The Committee for Orphan Medicinal Products (COMP)recommends orphan drug designation for rintatolimod for Pancreatic Cancer in the European Union [178] Updated 26 Feb 2021
16 Feb 2021 Trial Update AIM ImmunoTech in collaboration with Centre for Human Drug Research plans a AMP-COV-100 (CHDR2049) trial in COVID-2019 infections (Intranasal) in the first quarter of 2021 [10] [110] Updated 10 Mar 2021
16 Feb 2021 Regulatory Status AIM ImmunoTech receives approval from the required Ethics Committee in the Netherlands to commence its phase I AMP-COV-100 (CHDR2049) trial for prophylaxis or treatment for COVID-19 infections and other respiratory viral diseases [110] Updated 18 Feb 2021
10 Feb 2021 Regulatory Status AIM ImmunoTech plans for an IND and Clinical Trial application for rintatolimod in Pancreatic cancer in USA and the European Union [190] Updated 12 Feb 2021
10 Feb 2021 Regulatory Status AIM ImmunoTech intends to apply for Fast Track status for Pancreatic cancer in USA [190] Updated 12 Feb 2021
10 Feb 2021 Regulatory Status The Dutch Health and Youth Care Inspectorate (IGJ) approved follow-up Early Access Program (EAP) for Pancreatic cancer in the Netherlands [190] Updated 12 Feb 2021
29 Jan 2021 Licensing Status AIM ImmunoTech and Centre for Human Drug Research agree for clinical development in COVID-2019 infections [10] Updated 02 Feb 2021
06 Jan 2021 Trial Update AIM Immunotech initiates an expanded-access programme for Chronic Fatigue associated with COVID-2019 infections in USA [71] Updated 11 Jan 2021
31 Dec 2020 Trial Update AIM ImmunoTech plans a phase II/III trial for CIVID-2019 infections Updated 23 Apr 2021
17 Dec 2020 Regulatory Status Rintatolimod - AIM ImmunoTech receives Orphan Drug status for Pancreatic cancer in USA [179] Updated 22 Dec 2020
06 Oct 2020 Regulatory Status AIM ImmunoTech receives Institutional Review Board (IRB) approval for the expansion of the AMP 511 Expanded Access Program (EAP) clinical trial for Myalgic encephalomyelitis/Chronic fatigue syndrome [70] Updated 08 Oct 2020
06 Oct 2020 Trial Update AIM ImmunoTech plans an Expanded Access Program (EAP) clinical trial for Myalgic encephalomyelitis/Chronic fatigue syndrome [70] Updated 08 Oct 2020
28 Sep 2020 Regulatory Status AIM announced intention to file dual orphan drug status applications with the US FDA and EMA for use of Rintatolimod in Pancreatic cancer (Late-stage disease)in the US and in EU [188] Updated 29 Sep 2020
28 Sep 2020 Regulatory Status AIM announces intention to obtain US FDA's Fast-track and Breakthrough designation in Pancreatic cancer in USA [188] Updated 29 Sep 2020
28 Sep 2020 Scientific Update Efficacy results from a Early access programme for Rintatolimod in Pancreatic cancer (Late-stage disease, Metastatic disease) released by AIM ImmunoTech [188] Updated 29 Sep 2020
28 Sep 2020 Trial Update AIM announced intention to obtain IND authorisations to conduct a follow-up phase II/III clinical trial in Pancreatic cancer the Netherlands and in the US [188] Updated 29 Sep 2020
04 Sep 2020 Phase Change - I/II Phase-I/II clinical trials in COVID-2019 infections (Combination therapy) in USA (IV) (NCT04379518) Updated 18 Sep 2020
02 Sep 2020 Phase Change - Suspended(I/II) Suspended - Phase-I/II for Ovarian cancer (Neoadjuvant therapy, Second-line therapy or greater, Recurrent, Combination therapy, Late-stage disease) in USA (Intraperitoneal) Updated 06 Nov 2020
02 Sep 2020 Trial Update Roswell Park Cancer Institute, AIM ImmunoTech, National Cancer Institute and University of Pittsburgh suspend a phase I/II trial in Ovarian cancer (Combination therapy, Neoadjuvant therapy, Second-line therapy or greater, Recurrent, Late-stage disease) in USA (Intraperitoneal) (NCT02432378) Updated 14 Sep 2020
27 Aug 2020 Phase Change - Preclinical Preclinical trials in COVID-2019 infections (Prevention) in USA (Intranasal) [116] Updated 23 Nov 2020
27 Aug 2020 Phase Change - Preclinical Preclinical trials in COVID-2019 infections in USA (Intranasal) [116] Updated 23 Nov 2020
09 Jul 2020 Trial Update AIM ImmunoTech and Roswell Park Cancer Institute plans a phase I/IIb trial for COVID-2019 infections in cancer patients (Combination therapy) in USA (IV) in August 2020 (NCT04379518) [11] Updated 18 Sep 2020
09 Jul 2020 Licensing Status AIM ImmunoTech and Roswell Park Cancer institute entered into a clinical trial collaboration for COVID-2019 infections [11] Updated 15 Jul 2020
06 Jul 2020 Licensing Status AIM ImmunoTech signed a material transfer and research agreement with Japan's National Institute of Infectious Diseases (NIID) and Shionogi to test ampligen as a potential adjuvant therapy for COVID-19 [12] Updated 10 Jul 2020
05 Jul 2020 Phase Change - Discontinued(Preclinical) Discontinued - Preclinical for Ebola virus infections in Italy, USA (Intranasal) (AIM Immunotech pipeline, July 2020) Updated 05 Jul 2020
05 Jul 2020 Phase Change - Discontinued(Preclinical) Discontinued - Preclinical for West Nile virus infections in USA (unspecified route) (AIM Immunotech pipeline, July 2020) Updated 05 Jul 2020
05 Jul 2020 Phase Change - Discontinued(Preclinical) Discontinued - Preclinical for Zika virus infection in USA (Intranasal) (AIM Immunotech pipeline, July 2020) Updated 05 Jul 2020
17 Jun 2020 Regulatory Status AIM ImmunoTech receives import clearance from Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica (ANMAT) for rintatolimod for Chronic fatigue syndrome in Argentina [39] Updated 22 Jun 2020
16 Jun 2020 Patent Information AIM ImmunoTech files for patent protection for rintatolimod [231] Updated 16 Jun 2020
12 Jun 2020 Active Status Review Rintatolimod is still in phase II trials for Renal-cell carcinoma and malignant melanoma in USA [231] Updated 16 Jun 2020
14 May 2020 Regulatory Status The US FDA approves first human phase I/IIb trial for COVID-2019-infections (Combination therapy; in cancer patients) [104] Updated 20 May 2020
28 Apr 2020 Phase Change - No development reported No recent reports of development identified for preclinical development in Ebola-virus-infections in Italy (Intranasal, Spray) Updated 28 Apr 2020
28 Apr 2020 Phase Change - No development reported No recent reports of development identified for preclinical development in Ebola-virus-infections in USA (Intranasal, Spray) Updated 28 Apr 2020
28 Apr 2020 Phase Change - No development reported No recent reports of development identified for preclinical development in West Nile virus infections in USA Updated 28 Apr 2020
28 Apr 2020 Phase Change - No development reported No recent reports of development identified for preclinical development in Zika-virus-infection in USA (Intranasal) Updated 28 Apr 2020
28 Apr 2020 Phase Change - No development reported No recent reports of development identified for research development in Influenza-A-virus-infections in USA (IV) Updated 28 Apr 2020
26 Mar 2020 Trial Update AIM ImmunoTech plans clinical trials for COVID-2019 infections (Early-stage disease) in Argentina, Asia, Europe and USA (IV) [117] Updated 31 Mar 2020
26 Mar 2020 Trial Update AIM ImmunoTech plans clinical trials for COVID-2019 infections (Prevention) in Argentina, Asia, Europe and USA (Intranasal) [117] Updated 31 Mar 2020
26 Mar 2020 Trial Update AIM ImmunoTech plans clinical trials for COVID-2019 infections (Prevention) in Argentina, Asia, Europe and USA (PO) [117] Updated 31 Mar 2020
11 Feb 2020 Patent Information AIM ImmunoTech files three provisional patent applications for rintatolimod [120] Updated 24 Feb 2020
11 Feb 2020 Phase Change Early research in COVID-2019-infections (Prevention) in USA (Intranasal) [120] Updated 24 Feb 2020
11 Feb 2020 Phase Change - Preclinical Preclinical trials in COVID-2019-infections in USA (IV) before February 2020 [120] Updated 24 Feb 2020
11 Feb 2020 Scientific Update Preclinical pharmacodynamics data in COVID-2019-infections released by AIM ImmunoTech [120] Updated 24 Feb 2020
06 Dec 2019 Phase Change - I Phase-I clinical trials in Triple-negative-breast cancer (Combination therapy, Early-stage disease, Neoadjuvant therapy) in USA (IV) (NCT04081389) Updated 23 Aug 2021
29 Nov 2019 Phase Change - II Phase-II clinical trials in Prostate cancer (Combination therapy, Late-stage disease, Neoadjuvant therapy) in USA (IV) (NCT03899987) Updated 09 Dec 2019
24 Sep 2019 Regulatory Status Rintatolimod receives clearance from US FDA for exportation to Argentina for the treatment of Chronic fatigue syndrome [40] Updated 30 Sep 2019
09 Sep 2019 Trial Update Roswell Park Cancer Institute and National Cancer Institute plan a phase Ib/II trial in Breast cancer (Neoadjuvant therapy, First-line therapy, Combination therapy) in USA (IV), in September 2019 , (NCT04081389) Updated 23 Aug 2021
23 Aug 2019 Company Involvement Hemispherx Biopharma is now called AIM ImmunoTech Updated 05 Sep 2019
15 Aug 2019 Trial Update Hemispherx Biopharma plans a clinical trial for Breast cancer (Late-stage disease, Metastatic disease) in 2021 [217] [166] Updated 29 Nov 2021
15 Aug 2019 Trial Update Hemispherx Biopharma plans a clinical trial for Pancreatic cancer (Combination therapy) in Netherlands in 2019 [166] Updated 03 Jan 2020
15 Aug 2019 Trial Update Hemispherx Biopharma plans a phase I trial for Breast cancer (Combination therapy, Early-stage disease) in USA by 2020 [166] Updated 15 Oct 2019
15 Aug 2019 Regulatory Status The US FDA approves IND application for a phase II trial for rintatolimod in Prostate cancer (Combination therapy, Neoadjuvant therapy) [166] Updated 19 Aug 2019
15 Aug 2019 Trial Update Hemispherx Biopharma plans a phase II trial for Ovarian Cancer (Combination therapy, Recurrent, Second-line therapy or greater) (Intraperitoneal) [166] Updated 19 Aug 2019
17 Jun 2019 Trial Update Hemispherx Biopharma, Roswell Park Cancer Institute, and National Cancer Institute plan a phase II trial in Prostate cancer (Neoadjuvant therapy) in USA in June 2019 (NCT03899987) [240] Updated 09 Dec 2019
13 Mar 2019 Trial Update Hemispherx Biopharma and Roswell Park Cancer Institute plan a phase II trial for Colorectal cancer (Combination therapy, Late-stage disease; Metastatic disease, Second-line therapy or greater) in USA in 2019 [193] Updated 19 Aug 2019
13 Mar 2019 Trial Update Hemispherx Biopharma and Roswell Park Cancer Institute plan a clinical trial for Breast cancer (Inoperable/unresectable, Combination therapy, Metastatic disease, Second line therapy or greater) in USA in 2019 [193] Updated 09 Apr 2019
13 Mar 2019 Phase Change - Preclinical Preclinical trials in Prostate cancer in USA before March 2019 (IV) [193] Updated 15 Mar 2019
13 Mar 2019 Regulatory Status Hemispherx Biopharma files an IND application with the US FDA for a planned phase II trial in Prostate cancer (Neoadjuvant therapy) [193] Updated 15 Mar 2019
13 Mar 2019 Trial Update Hemispherx Biopharma and Roswell Park Cancer Institute plan a phase II trial for Bladder cancer, Melanoma and Renal cell carcinoma (Combination therapy, Late-stage disease, Second-line therapy or greater) in USA in 2019 [193] Updated 15 Mar 2019
13 Mar 2019 Trial Update Hemispherx Biopharma and University of Nebraska Medical Center plan a clinical trial for Non-small cell lung cancer (First-line therapy, Combination therapy) in USA in 2019 [193] Updated 15 Mar 2019
28 Feb 2019 Scientific Update Efficacy data from an Early Access Programme in Pancreatic cancer in Netherlands released by Hemispherx Biopharma [167] [193] Updated 19 Mar 2019
28 Feb 2019 Scientific Update Pharmacodynamics data from a preclinical trial in Pancreatic cancer released by Hemispherx Biopharma [167] Updated 07 Mar 2019
11 Feb 2019 Trial Update University of Pittsburgh in collaboration with Merck & Co and Hemispherx Biopharma initiates enrolment in a phase-I/II trial for Ovarian cancer (Combination therapy, Neoadjuvant therapy, Second-line therapy or greater) in USA [210] (NCT03734692) Updated 13 Feb 2019
09 Jan 2019 Phase Change - I Phase-I clinical trials in Breast cancer (Combination therapy, Metastatic disease, Second-line therapy or greater, Inoperable/Unresectable) in USA (IV) (NCT03599453) [170] Updated 09 Apr 2019
08 Jan 2019 Regulatory Status Institutional Review Board approves the initiation of a clinical trial of rintatolimod in Breast cancer [168] Updated 15 Jan 2019
31 Dec 2018 Trial Update Hemispherx Biopharma and Buffett Cancer Center plan a clinical trial for Non-small cell lung cancer in 2019 Updated 18 Mar 2022
12 Dec 2018 Trial Update Hemispherx Biopharma plans a phase I/II trial for Ovarian Cancer (Combination therapy, Recurrent, Second-line therapy or greater) in USA , (NCT03734692) [241] Updated 13 Feb 2019
12 Dec 2018 Trial Update Hemispherx Biopharma plans additional clinical trials for Cancer in 2019 [241] Updated 19 Dec 2018
13 Aug 2018 Trial Update Hemispherx Biopharma plans a phase I and phase II trials for Cancer in combination with checkpoint inhibitors [84] Updated 20 Aug 2018
09 Jul 2018 Scientific Update Adverse events and immunogenicity data from a phase I/II trial in Influenza virus infections released by Hemispherx Biopharma [146] Updated 11 Jul 2018
15 Jun 2018 Trial Update Hemispherx Biopharma plans a phase I/II trial for Solid tumours (Combination therapy) in USA [56] Updated 20 Jun 2018
02 May 2018 Trial Update Hemispherx Biopharma plans phase I/II trial for Cancer (in combination with checkpoint inhibitors) Updated 07 May 2018
17 Apr 2018 Regulatory Status US FDA approves a Compassionate Care Programme for Myalgic encephalomyelitis/Chronic fatigue syndrome before April 2018 [57] Updated 20 Apr 2018
17 Apr 2018 Trial Update Hemispherx Biopharma plans a Compassionate Care Programme for Myalgic encephalomyelitis/Chronic fatigue syndrome (ME/CFS) in USA [57] Updated 20 Apr 2018
04 Apr 2018 Regulatory Status Hemispherx Biopharma intends to initiate a Special Access Program (SAP) for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Canada in May 2018 [17] Updated 29 Oct 2018
04 Apr 2018 Licensing Status Hemispherx amends its agreement with myTomorrows to expands rintatolimod Early Access Programme for Chronic fatigue syndrome to Canada [17] Updated 09 Apr 2018
27 Mar 2018 Phase Change - II Phase-II clinical trials in Colorectal cancer (Combination therapy, Metastatic disease, Second-line therapy or greater, Recurrent, Inoperable/Unresectable) in USA (IV) (NCT03403634) Updated 07 May 2018
27 Mar 2018 Other Chemical structure information added Updated 27 Mar 2018
14 Mar 2018 Licensing Status University of Nebraska Medical Center and Hemispherx Biopharma agree to test the combined efficacy of rintatolimod and peptide vaccine for Pancreatic cancer [19] Updated 20 Mar 2018
26 Feb 2018 Regulatory Status Hemispherx Biopharma plans to supply Ampligen® for pancreatic cancer patients in Canada under a Special Access Program (SAP) in May 2018 [191] Updated 20 Jun 2018
06 Feb 2018 Trial Update Hemispherx Biopharma terminates a phase I/II trial in Colorectal cancer (Neoadjuvant therapy, Metastatic disease, Recurrent) in USA (IV) (NCT01545141) Updated 06 Feb 2018
31 Jan 2018 Scientific Update Immunogenicity data from a phase I/II trial in Influenza virus infections released by Hemispherx Biopharma [147] Updated 05 Feb 2018
31 Jan 2018 Scientific Update Pharmacodynamics data from a preclinical trial in Influenza virus infections released by Hemispherx Biopharma [147] Updated 05 Feb 2018
23 Jan 2018 Regulatory Status Hemispherx Biopharma announces intention to launch rintatolimod for Chronic fatigue syndrome in Argentina Updated 29 Jan 2018
18 Jan 2018 Trial Update Roswell Park Cancer Institute and National Cancer Institute plan a early phase IIa trial for Colorectal cancer (Metastatic disease, Combination therapy) in USA in February 2018 (NCT03403634) Updated 25 Jul 2018
20 Dec 2017 Active Status Review Rintatolimod is still in preregistration phase for Chronic fatigue syndrome in USA [36] Updated 09 Apr 2018
13 Aug 2017 Phase Change - I Phase-I clinical trials in Pancreatic cancer (Late-stage disease) in Netherlands (IV) (AIM ImmunoTech pipeline, August 2019) Updated 03 Jan 2020
08 Aug 2017 Licensing Status Rintatolimod is available for licensing in Canada as of 08 Aug 2017. http://www.hemispherx.net/ [58] Updated 10 Aug 2017
04 Aug 2017 Regulatory Status Hemispherx Biopharma announces intention to submit applications for Early Access Programs (EAP) in Europe and additional countries in 2018 [242] Updated 05 Mar 2018
11 Jul 2017 Trial Update Hemispherx Biopharma plans clinical trials for Cancer [156] Updated 27 Jul 2017
23 Feb 2017 Trial Update Hemispherx Biopharma terminates a phase I/II trial in Influenza virus infection (Combination therapy, Prevention, In volunteers) in USA as CDC indicated nasal spray flu vaccine should not be used during 2016-2017 (NCT01591473) Updated 02 Nov 2017
11 Jan 2017 Phase Change - Clinical Clinical trials in Pancreatic cancer in Netherlands (IV) [15] Updated 10 Jun 2017
11 Jan 2017 Regulatory Status European Early access programme for rintatolimod has been extended to include pancreatic cancer patients [15] Updated 16 Jan 2017
31 Dec 2016 Patent Information Hemispherx Biopharma has a patent protection for composition of matter of rintatolimod in USA [65] before December 2016 Updated 16 Jun 2017
31 Oct 2016 Scientific Update Updated retrospective analysis of efficacy data from a phase III trial in Chronic fatigue syndrome released by Hemispherx Biopharma [62] Updated 07 Nov 2016
31 Oct 2016 Trial Update Hemispherx Biopharma plans a confirmatory phase III trial for Chronic fatigue syndrome in USA [62] Updated 07 Nov 2016
23 Aug 2016 Phase Change - Registered Registered for Chronic fatigue syndrome in Argentina (IV) - First global approval [41] Updated 25 Aug 2016
25 Jul 2016 Regulatory Status Rintatolimod is available on an Early Access Programme for the treatment of Chronic fatigue syndrome in Europe [14] Updated 28 Jul 2016
06 Jun 2016 Licensing Status Hemispherx irrevocabaly obtains all intellectual property related to Ampligen® under a comprehensive omnibus assignment [20] Updated 09 Jun 2016
31 May 2016 Active Status Review Rintatolimod is still in preregistration for Chronic fatigue syndrome in Argentina Updated 06 Jun 2016
31 May 2016 Licensing Status Hemispherx renews the sales, marketing, distribution and supply agreement with GP Pharm for rintatolimod in Argentina for the treatment of chronic fatigue syndrome [25] Updated 06 Jun 2016
16 Mar 2016 Trial Update Hemispherx complete a phase II trial in Chronic fatigue syndrome before 2016 [82] Updated 16 Mar 2016
09 Feb 2016 Trial Update Hemispherx plans a clinical trial for Zika virus infections [154] Updated 11 Feb 2016
03 Feb 2016 Phase Change - Preclinical Preclinical trials in West Nile virus infections in USA (unspecified route) Updated 17 Feb 2016
03 Feb 2016 Phase Change - Preclinical Preclinical trials in Zika virus infection in USA (Intranasal) Updated 11 Feb 2016
21 Sep 2015 Scientific Update Retrospective analysis of efficacy data from a phase III trial in Chronic fatigue syndrome released by Hemispherx Biopharma [77] Updated 19 Oct 2015
21 Sep 2015 Patent Information Hemispherx Biopharma has patent protection for composition of matter of rintatolimod in the European Union [233] Updated 11 Oct 2015
17 Sep 2015 Regulatory Status Rintatolimod is available on a Named Patient Access Programme, under the AMP-511 study, for the treatment of Chronic fatigue syndrome in USA (IV) [64] Updated 16 Jun 2017
15 Sep 2015 Scientific Update Interim pharmacodynamics data from a Preclinical study in Chronic fatigue syndrome released by hemispherx Biopharma [87] Updated 07 Oct 2015
04 Sep 2015 Phase Change - I/II Phase-I/II clinical trials in Ovarian cancer (Combination therapy, Neoadjuvant therapy, Second-line therapy or greater, Recurrent, Late-stage disease) in USA (Intraperitoneal) (NCT02432378) Updated 13 Jan 2016
10 Aug 2015 Licensing Status Rintatolimod licensed to myTomorrows for implementation of Early Access Programme for the treatment of Chronic fatigue syndrome in Europe and Turkey [13] Updated 19 Aug 2015
10 Aug 2015 Regulatory Status Celsion plans for regulatory approval worldwide, including Europe, Latin America, Australia, New Zealand and USA [13] Updated 19 Aug 2015
25 Jun 2015 Patent Information Hemispherx Biopharma receives patent allowance for composition of matter of rintatolimod in Europe [234] Updated 27 Jun 2015
11 May 2015 Regulatory Status Rintatolimod receives Orphan Drug status for Ebola virus infections in European Union [130] Updated 13 May 2015
24 Mar 2015 Phase Change - Preclinical Preclinical trials in Ebola virus infections in Italy (Intranasal) [131] Updated 30 Mar 2015
24 Mar 2015 Regulatory Status The Committee for Orphan Medicinal Products (COMP) recommends orphan drug designation for rintatolimod in European Union for Ebola virus infections [131] Updated 30 Mar 2015
23 Mar 2015 Phase Change - Discontinued(Preclinical) Discontinued - Preclinical for Western equine encephalitis virus infections in USA (IV) Updated 13 Apr 2015
09 Mar 2015 Licensing Status Rintatolimod licensed to Emerge Health in Australia and New Zealand [21] Updated 14 Mar 2015
12 Feb 2015 Scientific Update Pharmacodynamics data from a preclinical study in Ebola virus infections released by Hemispherx Biopharma [133] Updated 12 Feb 2015
09 Feb 2015 Scientific Update Updated pharmacodynamics data from a preclinical study in Ebola virus infections released by Hemispherx Biopharma [132] Updated 12 Feb 2015
02 Feb 2015 Phase Change - Preclinical Preclinical trials in Ebola virus infections in USA (Intranasal) prior to February 2015 Updated 04 Feb 2015
12 Jan 2015 Scientific Update Efficacy data from a phase III trial in Chronic fatigue syndrome released by Hemispherx [88] Updated 19 Jan 2015
31 Dec 2014 Active Status Review Rintatolimod is still in preregistration for Chronic fatigue syndrome in USA and Argentina Updated 16 Apr 2015
17 Nov 2014 Scientific Update Pharmacodynamics data from an in vitro study in Ebola virus infection released by Hemispherx [138] Updated 20 Nov 2014
29 Sep 2014 Company Involvement Hemispherx enters into five research collaborations to develop therapeutic cocktails against Ebola virus infections [23] Updated 01 Oct 2014
10 Sep 2014 Phase Change Early research in Ebola virus infections in USA (Intranasal) Updated 03 Nov 2014
10 Sep 2014 Company Involvement Hemispherx establishes a research agreement with Swiss Department of Defense, Civil Protection and Sports for the development of Rintatolimod in Ebola virus infections [22] Updated 15 Sep 2014
14 Jul 2014 Licensing Status Hemispherx Biopharma and Bioclones agree to co-develop rinatatolimod in South Africa [24] Updated 18 Jul 2014
01 Jul 2014 Phase Change - I/II Phase-I/II clinical trials in Peritoneal cancer (Adjuvant therapy) in USA (IV) Updated 25 Nov 2014
28 May 2014 Trial Update University of Pittsburgh plans a phase I/II trial for Peritoneal cancer (adjuvant therapy) in USA (NCT02151448) Updated 29 Jul 2014
10 Mar 2014 Regulatory Status Hemispherx Biopharma announces intention to submit regulatory filings in Chile, Peru & Uruguay for Chronic fatigue syndrome [61] Updated 11 Mar 2014
01 Dec 2013 Regulatory Status Rintatolimod receives Orphan Drug status for HIV infections in USA Updated 02 Jul 2014
01 Dec 2013 Regulatory Status Rintatolimod receives Orphan Drug status for Malignant melanoma in USA Updated 02 Jul 2014
01 Dec 2013 Regulatory Status Rintatolimod receives Orphan Drug status for Renal cell carcinoma in USA Updated 02 Jul 2014
12 Sep 2013 Phase Change Early research in Coronavirus infections in USA (IV) Updated 18 Sep 2013
12 Sep 2013 Phase Change Early research in Influenza-A virus infections in USA (IV) Updated 18 Sep 2013
12 Sep 2013 Phase Change Early research in Alphavirus Infections in USA (IV) Updated 18 Sep 2013
04 Feb 2013 Regulatory Status The US FDA issues a Complete Response Letter declining to approve an NDA for rintatolimod for the treatment of Chronic fatigue syndrome [37] Updated 07 Feb 2013
01 Oct 2012 Phase Change - I/II Phase-I/II clinical trials in Colorectal cancer (Neoadjuvant therapy, Metastatic disease, Recurrent) in USA (IV) (NCT01545141) Updated 25 Nov 2014
14 Aug 2012 Regulatory Status The US FDA sets PDUFA date of February 2013 for NDA review for Chronic fatigue syndrome Updated 15 Aug 2012
01 Aug 2012 Regulatory Status Hemispherix Biopharma files its complete response to the US FDA's Complete Response Letter for rintatolimod in Chronic fatigue syndrome [45] Updated 02 Aug 2012
18 Jul 2012 Phase Change - Preregistration Preregistration for Chronic fatigue syndrome in Argentina (IV) Updated 19 Jul 2012
01 Apr 2012 Phase Change - I/II Phase-I/II clinical trials in Influenza virus infections (Combination therapy, In volunteers, Prevention) in USA (Intranasal) (NCT01591473) Updated 16 Nov 2017
19 Mar 2012 Scientific Update Efficacy and adverse event data from a phase III trial in Chronic fatigue syndrome released by Hemispherx Biopharma [49] Updated 20 Mar 2012
01 Jan 2012 Phase Change - No development reported(Preclinical) No development reported - Preclinical for Western equine encephalitis virus infections in USA (IV) Updated 13 Apr 2015
31 Aug 2011 Phase Change - I/II Phase-I/II clinical trials in Cancer (adjuvant in breast cancer vaccination trial) in USA (Injection) Updated 15 Dec 2011
01 Jul 2011 Phase Change - I/II Phase-I/II clinical trials in Triple-negative-breast cancer (Adjuvant therapy) in USA (Intradermal) Updated 25 Nov 2014
04 Apr 2011 Phase Change - Preclinical Preclinical trials in Cancer in USA (Injection) Updated 08 Apr 2011
04 Apr 2011 Scientific Update Pharmacodynamics data from a preclinical study in Cancer released by Hemispherx Biopharma [208] Updated 08 Apr 2011
01 Mar 2011 Phase Change - I/II Phase-I/II clinical trials in Ovarian cancer (Adjuvant therapy) in USA (IV) Updated 25 Nov 2014
04 Feb 2011 Phase Change - Suspended(II) Suspended - Phase-II for HIV infections in USA (IV) Updated 04 Feb 2011
14 Dec 2010 Regulatory Status The FDA grants Hemispherx a 12 month extension to modify its rintatolimod NDA Updated 20 Dec 2010
09 Dec 2010 Licensing Status Rintatolimod licensed to GP Pharm in Mexico [26] Updated 17 Dec 2010
29 Nov 2010 Regulatory Status Hemispherx files a request with the FDA to maintain an active NDA for rintatolimod to treat Chronic fatigue syndrome [48] Updated 03 Dec 2010
10 Nov 2010 Company Involvement Hemispherx receives grant through the US Qualifying Therapeutic Discovery Project programme for rintatolimod development in Chronic fatigue syndrome [222] Updated 15 Nov 2010
30 Sep 2010 Licensing Status Rintatolimod is available for licensing as of 30 Sep 2010. http://www.hemispherx.net Updated 28 Jan 2011
08 Sep 2010 Scientific Update Topline efficacy data from a phase III trial in chronic fatigue syndrome released by Hemispherx [243] Updated 10 Sep 2010
08 Jul 2010 Active Status Review Rintatolimod is still in preregistration for Chronic fatigue syndrome in USA Updated 08 Jul 2010
17 Jun 2010 Licensing Status Hemispherx enters into a sales, marketing distribution and supply agreement with GP Pharm Latinoamerica for rintatolimod in the treatment of chronic fatigue syndrome in Argentina [27] Updated 17 Jun 2010
08 Apr 2010 Trial Update Hemispherx Biopharma completes phase II trials in HIV infections Updated 15 Apr 2010
08 Feb 2010 Phase Change - Discontinued(Preclinical) Discontinued - Preclinical for Smallpox in USA (IV) Updated 08 Feb 2010
01 Dec 2009 Regulatory Status Hemispherx Biopharma receives complete response letter from the US FDA for rintatolimod in Chronic fatigue syndrome [53] Updated 07 Dec 2009
22 Oct 2009 Scientific Update Pharmacodynamics data from a preclinical study in macaque monkeys in Influenza virus infections released by Hemispherx Biopharma [244] Updated 28 Oct 2009
26 May 2009 Regulatory Status The US FDA advises Hemispherx Biopharma of a possible brief delay in its action report for the NDA filing of rintatolimod for Chronic fatigue syndrome Updated 11 Jun 2009
18 Feb 2009 Regulatory Status The US FDA extends the PDUFA review date for the NDA filing of rintatolimod for Chronic fatigue syndrome Updated 03 Mar 2009
01 Jan 2009 Phase Change - Preclinical Preclinical trials in Western equine encephalitis virus infections in USA (IV) Updated 13 Apr 2015
18 Nov 2008 Company Involvement Hemispherx Biopharma enters into a research contract agreement with Lovelace Respiratory Research Institute to conduct additional preclinical studies with rintatolimod for Chronic fatigue syndrome in USA [28] Updated 03 Dec 2008
08 Jul 2008 Regulatory Status The US FDA accepts Hemispherx Biopharma's NDA filing of rintatolimod for review in Chronic fatigue syndrome Updated 22 Jul 2008
06 Mar 2008 Regulatory Status Hemispherx Biopharma reaches agreement with the US FDA on specific steps to achieve completion of NDA filing for rintatolimod in Chronic fatigue syndrome Updated 18 Mar 2008
09 Jan 2008 Regulatory Status Hemispherx Biopharma formally submits detailed responses to address questions raised by the US FDA concerning the NDA filing for rintatolimod in Chronic fatigue syndrome Updated 23 Jan 2008
10 Dec 2007 Licensing Status Hemispherx Biopharma intends to terminate its licence agreement with Esteve Updated 19 Dec 2007
05 Dec 2007 Regulatory Status Hemispherx Biopharma receives notification from the US FDA that the NDA filing for rintatolimod in Chronic fatigue syndrome is incomplete; FDA review is postponed Updated 19 Dec 2007
11 Oct 2007 Phase Change - Preregistration Preregistration for Chronic fatigue syndrome in USA (IV) Updated 24 Oct 2007
11 Jun 2007 Scientific Update Preclinical data added to the Viral Infections pharmacodynamics section [245] Updated 11 Jun 2007
16 Mar 2007 Phase Change - Suspended(II) Suspended - Phase-II for HIV infections treatment in USA (IV) Updated 27 Sep 2007
05 Sep 2006 Phase Change - No development reported(Clinical) No development reported - Clinical-Phase-Unknown for Chronic fatigue syndrome in Australia (IV) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(Clinical) No development reported - Clinical-Phase-Unknown for Chronic fatigue syndrome in South Africa (IV) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(II) No development reported - Phase-II for Chronic fatigue syndrome in Belgium (IV) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(II) No development reported - Phase-II for Hepatitis B in USA (IV) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(II) No development reported - Phase-II for HIV infections treatment in Spain (unspecified route) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(II) No development reported - Phase-II for Malignant melanoma in USA (IV) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(II) No development reported - Phase-II for Renal cell carcinoma in USA (IV) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(III) No development reported - Phase-III for HIV infections treatment in European Union (unspecified route) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(Preclinical) No development reported - Preclinical for Smallpox in USA (IV) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(Preregistration) No development reported - Preregistration for Chronic fatigue syndrome in Canada (IV) Updated 05 Sep 2006
05 Sep 2006 Phase Change - No development reported(Preregistration) No development reported - Preregistration for Chronic fatigue syndrome in European Union (IV) Updated 05 Sep 2006
03 Mar 2006 Scientific Update Preclinical data from a media release have been added to the Viral infections immunogenicity section [246] Updated 03 Mar 2006
18 Oct 2005 Trial Update Phase III trials have been completed in Chronic fatigue syndrome Updated 18 Oct 2005
17 Aug 2005 Phase Change - II Phase-II clinical trials in HIV infections treatment in USA (IV) Updated 19 May 2009
13 Apr 2005 Scientific Update Data from a media release have been added to the Neurological Disorders therapeutic trials section [247] Updated 13 Apr 2005
06 Jan 2005 Phase Change - II Phase-II clinical trials in HIV infections treatment in patients with or without Hepatitis C virus co-infection in Spain (IV) Updated 06 Jan 2005
13 Oct 2004 Scientific Update Clinical data from a media release have been added to the adverse events section [248] Updated 13 Oct 2004
13 Jul 2004 Regulatory Status Esteve Laboratorios has received import authorisation from the Spanish Ministry of Health for Ampligen® to conduct clinical trials in HIV/HCV coinfected patients Updated 13 Jul 2004
01 Jun 2004 Scientific Update Data presented at the 17th International Conference on Antiviral Research (ICAR-2004) have been added to the Neurological disorders therapeutic trials section [249] Updated 01 Jun 2004
05 May 2004 Scientific Update Data from a media release have been added to the Neurological disorders therapeutic trials section [76] Updated 05 May 2004
04 Feb 2004 Trial Update Hemispherx has completed a phase III trial in CFS in USA Updated 04 Feb 2004
01 Feb 2004 Trial Update Hemispherx Biopharma completes a phase III trial in Chronic Fatigue Syndrome in USA (IV) (NCT00215800) Updated 10 Aug 2017
30 Oct 2003 Phase Change Mismatched double stranded RNA has received Orphan Drug Status for Chronic fatigue syndrome in USA Updated 04 Aug 2004
08 Sep 2003 Licensing Status Hemispherx Biopharma has entered into an agreement with Guandong Medicine Group Corporation to organise clinical trials, market, sell and distribute Interferon-α-n3 in China for HIV infections treatment Updated 08 Sep 2003
12 May 2003 Licensing Status Hemispherx Biopharma has entered into an agreement with the Center for Cell and Gene Therapy to implement Ampligen in relapsed EBV-positive Hodgkins lymphoma [34] . Updated 12 May 2003
06 May 2003 Scientific Update Data presented at the 16th International Conference on Antiviral Research (ICAR-2003) have been added to the Viral infections therapeutic trials section [250] Updated 06 May 2003
23 Dec 2002 Scientific Update Data from a media release have been added to the Viral Infections therapeutic trials section [251] Updated 23 Dec 2002
09 Dec 2002 Trial Update Hemispherx has completed enrolment in a phase III trial for Chronic fatigue syndrome in the US Updated 19 Feb 2003
27 Nov 2002 Scientific Update A study has been added to the adverse events and Viral Infections therapeutic trials sections [252] Updated 27 Nov 2002
31 Mar 2002 Licensing Status Hemispherx Biopharma's mismatched double stranded RNA licensed to Esteve in Spain, Portugal and Andorra for Chronic fatigue syndrome Updated 19 Dec 2007
25 Mar 2002 Scientific Update Preliminary data have been added to the Viral Infections therapeutic trials section [253] Updated 25 Mar 2002
31 Dec 2001 Scientific Update A study has been added to the Viral Infections antimicrobial acivity and drug interactions sections [254] Updated 31 Dec 2001
21 Dec 2001 Phase Change - Preclinical Preclinical development for Smallpox in USA (Unknown route) Updated 21 Dec 2001
21 Feb 2001 Phase Change - III Phase-III clinical trials for HIV infections treatment in European Union (IV) Updated 21 Feb 2001
02 Feb 2001 Trial Update Hemispherx has modified the protocol for its phase II HIV trial Updated 02 Feb 2001
12 Jan 2001 Regulatory Status US FDA approves a phase II trial protocol for patients with early-stage HIV Updated 12 Jan 2001
24 Oct 2000 Phase Change - Preregistration Preregistration for Chronic fatigue syndrome in Canada (IV) Updated 24 Oct 2000
20 Oct 2000 Regulatory Status Hemispherx Europe receives Orphan Drug Status for Mismatched double stranded RNA for the treatment of Chronic fatigue syndrome in the European Union Updated 20 Oct 2000
20 Oct 2000 Regulatory Status Hemispherx has expanded treatment protocols to the European Union Updated 20 Oct 2000
31 Aug 2000 Phase Change Investigation in Chronic fatigue syndrome in South Africa (IV) Updated 31 Aug 2000
30 Jun 2000 Regulatory Status The FDA has approved a phase II/III trial in patients with HIV infection resistant to currently available treatments Updated 30 Jun 2000
26 May 2000 Phase Change Investigation in Chronic fatigue syndrome in Australia (IV) Updated 26 May 2000
25 Feb 2000 Regulatory Status Hemispherx Biopharma has filed an application for expanded access for HIV patients and phase I/II trials with the US FDA Updated 25 Feb 2000
18 Feb 2000 Licensing Status Mismatched double stranded RNA licensed to Biovail Corporation in Canada Updated 18 Feb 2000
10 Dec 1999 Company Involvement An agreement with Schering-Plough has been reached in the US for production of Mismatched double stranded RNA Updated 10 Dec 1999
13 Sep 1999 Scientific Update Pharmacoeconomics data from a Clinical trial in Chronic fatigue syndrome released by Hemispherx Biopharma [255] Updated 21 Oct 1999
10 Dec 1998 Phase Change - Preregistration Preregistration for Chronic fatigue syndrome in European Union (IV) Updated 10 Dec 1998
13 Oct 1998 Scientific Update A study has been added to the Viral infections antimicrobial section [256] Updated 13 Oct 1998
23 Jan 1997 Phase Change - II Phase-II clinical trials for Chronic fatigue syndrome in Belgium (IV) Updated 23 Jan 1997
23 Jan 1997 Phase Change - II Phase-II clinical trials for HIV infections treatment in USA (IV) Updated 23 Jan 1997
05 Dec 1996 Phase Change Investigation in Chronic fatigue syndrome in Belgium (IV) Updated 05 Dec 1996
05 Dec 1996 Phase Change Investigation in Chronic fatigue syndrome in Canada (IV) Updated 05 Dec 1996
21 Oct 1996 Scientific Update A study has been added to the Nervous system disorders therapeutic trials section Updated 21 Oct 1996
17 Oct 1996 Scientific Update A study has been added to the therapeutic trials section [257] Updated 17 Oct 1996
26 Feb 1996 Phase Change - III Phase-III clinical trials for Chronic fatigue syndrome in USA (IV) Updated 26 Feb 1996
16 Feb 1996 Phase Change - II Phase-II clinical trials for Renal cell carcinoma in USA (IV) Updated 16 Feb 1996
28 Apr 1995 Phase Change - II Phase-II clinical trials for Malignant melanoma in USA (IV) Updated 28 Apr 1995
12 Apr 1995 Scientific Update A study has been added to the Cancer therapeutic trials section [258] Updated 12 Apr 1995

References

  1. Hemispherx Highlights Year-To-Date Progress, Outlines Key Objectives.

    Media Release
  2. AIM ImmunoTech Engages Business Development Firm, Azenova, LLC to Catalyze Partnering, Development and Commercialization Efforts for Ampligen(Rm) Pipeline Programs.

    Media Release
  3. Hemispherx Biopharma Signs Clinical Trial Agreement with Roswell Park Comprehensive Cancer Center to Study Ampligen in Combination with Checkpoint Inhibitors in a Phase IIa Study in Urothelial Carcinoma, Renal Cell Carcinoma and Melanoma.

    Media Release
  4. Hemispherx Biopharma, Inc. Changes Name to AIM ImmunoTech Inc. Reflecting Ampligen's(Rm) Immuno Modulation Progress in Ongoing Oncology Clinical Trials and ME/CFS.

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  5. AIM ImmunoTech Enters into Pancreatic Cancer Clinical Research Agreements with AstraZeneca and Erasmus Medical Center.

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  6. AIM ImmunoTech Announces Phase 2a Human Challenge Trial to Test its Drug Ampligen as an Intranasal Antiviral Prophylactic Therapy.

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  7. AIM ImmunoTech Announces Clinical Trial Agreement for a Phase 2a Human Challenge Trial of Ampligen as a Potential Intranasal Prophylaxis Against Respiratory Viruses.

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  10. AIM ImmunoTech Enters into Agreement for Proposed Intranasal Safety Study of Ampligen.

    Media Release
  11. AIM ImmunoTech Signs Clinical Trial Agreement with Roswell Park Comprehensive Cancer Center Supporting Phase 1/2 Clinical Trial of Ampligen Combined with Interferon Alfa-2b in COVID-19 Patients with Cancer.

    Media Release
  12. AIM ImmunoTech Signs Material Transfer and Research Agreement with Japan's National Institute of Infectious Diseases and Shionogi, a Leading Global Pharmaceutical Company, to Test Ampligen as Potential Vaccine Adjuvant for COVID-19.

    Media Release
  13. Hemispherx Enters Into an Agreement With myTomorrows for an Early Access Program for Rintatolimod in Europe.

    Media Release
  14. Hemispherx Announces First Shipment of Rintatolimod (Ampligen(R)) to Early Access Program in Europe.

    Media Release
  15. Hemispherx Biopharma Announces Extension of Rintatolimod European Early Access Program (EAP) to Pancreatic Cancer Patients.

    Media Release
  16. Hemispherx Biopharma Announces Financial Results for the Year Ended December 31, 2016.

    Media Release
  17. Hemispherx Expands Ampligen Early Access Programme to Canada to Treat ME/CFS Patients.

    Media Release
  18. Hemispherx Announces New Data Showing Ampligens Positive Role in Reprograming Tumor Microenvironment.

    Media Release
  19. Hemispherx Biopharma and UNMC Partner to Take on Pancreatic Cancer.

    Media Release
  20. Hemispherx Biopharma Obtains a Comprehensive Carter Omnibus Assignment of Intellectual Property.

    Media Release
  21. Hemispherx Enters a Collaboration with Emerge Health for the Commercialization of Ampligen for Chronic Fatigue Syndrome (CFS) in Australia and New Zealand.

    Media Release
  22. Hemispherx Biopharma and the Swiss Department of Defense, Civil Protection and Sports Expand Their Collaborative Research Agreement to Include the Study of Alferon(Rm) and Ampligen(Rm) Against the Ebola Virus.

    Media Release
  23. Hemispherx Biopharma Expands Research on Potential Ebola Treatments to Five Independent Experts/Institutional Collaborators.

    Media Release
  24. Hemispherx Biopharma and Bioclones, a Leading South African Biotechnology Company, Join Forces on Novel Therapeutic Cancer Vaccine.

    Media Release
  25. Hemispherx Biopharma Renews Sales, Marketing, Distribution and Supply Agreement with GP Pharm.

    Media Release
  26. Hemispherx Biopharma Extends GP Pharm License to Mexico for Ampligen to Treat for Chronic Fatigue Syndrome in Latin America.

    Media Release
  27. Hemispherx Biopharma Licenses Platform Technologies to GP Pharm.

    Media Release
  28. Hemispherx Enters Major Contract With Lovelace Respiratory Institute.

    Media Release
  29. Hemispherx Biopharma Intends to Terminate License to Esteve for the Marketing of Ampigen for Chronic Fatigue Syndrome in Certain Territories.

    Media Release
  30. Hemispherx Biopharma, Inc. 2nd Quarter 2010 Financial Results.

    Media Release
  31. Hemispherx Biopharma, Inc. Releases Financial Results for the Three Months Ended June 30, 2008.

    Media Release
  32. Hemispherx Biopharma Signs Option Agreement for Ampligen with Fujisawa Pharmaceutical Company.

    Media Release
  33. Hemispherx Biopharma Signs Agreement with Guangdong Medicine Group Corporation.

    Media Release
  34. Hemispherx Biopharma Enters Into Therapeutic Agreement for Ampligen(R) With The Center for Cell and Gene Therapy at Baylor College of Medicine.

    Media Release
  35. Hemispherx Biopharma Signs Letter of Intent with HollisterStier Laboratories LLC for the Production of Ampligen(R).

    Media Release
  36. Hemispherx Successfully Completes Commercial Scale Demonstration Batch of Ampligen(R) at Contract Manufacturer.

    Media Release
  37. Hemispherx Biopharma Receives Complete Response Letter from FDA on Ampligen(Rm) New Drug Application for Chronic Fatigue Syndrome.

    Media Release
  38. International Stem Cell Corporation to Raise $6.3 Million Through a Private Placement to Fund Phase I Clinical Trial.

    Media Release
  39. AIM ImmunoTech Provides Update on Commercial Launch of Ampligen(R) in Argentina for the Treatment of Chronic Fatigue Syndrome.

    Media Release
  40. AIM ImmunoTech's Ampligen Receives Clearance from FDA for Exportation to Argentina for the Treatment of Severe Chronic Fatigue Syndrome.

    Media Release
  41. Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen(R)) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic.

    Media Release
  42. Hemispherx Biopharma Announces Filing a New Drug Application in Argentina for Ampligen(R) to Treat Chronic Fatigue Syndrome.

    Media Release
  43. Hemispherx Biopharma Announces FDA Advisory Committee Will Review Ampligen(R) for Chronic Fatigue Syndrome

    Media Release
  44. FDA Accepts Complete Response Submission Regarding the Ampligen(R) New Drug Application for Chronic Fatigue Syndrome.

    Media Release
  45. Hemispherx Biopharma Files Complete Response With the FDA Regarding Its Ampligen(R) New Drug Application for Chronic Fatigue Syndrome.

    Media Release
  46. FDA Grants Hemispherx Biopharma Extension in Its Pending New Drug Application (NDA) for the Treatment of Chronic Fatigue Syndrome (CFS).

    Media Release
  47. FDA Grants Hemispherx Biopharma Extension in Its Pending NDA for Treatment of Chronic Fatigue Syndrome (CFS).

    Media Release
  48. Hemispherx Biopharma Files With the FDA a Request to Maintain as Active Hemispherx NDA for Ampligen(R) to Treat Chronic Fatigue Syndrome (CFS).

    Media Release
  49. Hemispherx Publishes Data on the Bioactivity of Ampligen(R) in Chronic Fatigue Syndrome ("CFS").

    Media Release
  50. Hemispherx Biopharma and the FDA Reach Agreement on Filing Requirements for the Company's Complete Response in Support of Ampligen(R) New Drug Application for Chronic Fatigue Syndrome Treatment.

    Media Release
  51. FDA Advisory Committee Makes Recommendations on Ampligen (R) for Chronic Fatigue Syndrome.

    Media Release
  52. Hemispherx Biopharma's Ampligen NDA for Chronic Fatigue Syndrome Accepted for Review by the FDA.

    Media Release
  53. Hemispherx Biopharma Receives Complete Response Letter From FDA on Ampligen(R) New Drug Application for Chronic Fatigue Syndrome.

    Media Release
  54. Hemispherx Biopharma Addresses Ampligen(R) CFS Preclinical Issues.

    Media Release
  55. Hemispherx Biopharma Addresses Ampligen(R) Manufacturing Issues.

    Media Release
  56. Hemispherx Releases First 8,500 Vial Lot of Ampligen to Supply Expanded Access Programs in the United States, Europe and Canada for ME/CFS and Pancreatic Cancer and Announces Successful Finish of Second Commercial Size Lot.

    Media Release
  57. Hemispherx Successfully Completes Production of More Than 8,500 Vials of Ampligen for Commercial Sales and Expanded Clinical Programs.

    Media Release
  58. Hemispherx Biopharma Announces Collaboration with Millions Missing Canada to Bring Medication to Canadians for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

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  59. Hemispherx Biopharma, Inc. Meets Ampligen Sales Milestone in the 1st Quarter of 2017.

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  60. Hemispherx Biopharma Announces Completion of Ampligen(R) Manufacturing Technology Transfer Milestone.

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  61. Hemispherx Biopharma Announces Plans to File for Regulatory Approval of Ampligen(Rm) to Treat Chronic Fatigue Syndrome (CFS) in Three Additional Latin America Countries.

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  62. Hemispherx Biopharma Announces Identification of High Responder Patient Subgroup from Ampligen(R) Phase III Trial in Patients with CFS/ME.

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  63. An Open-Label Study Of Poly I:Poly C12U (AMPLIGEN) in Patients With Severely Debilitating Chronic Fatigue Syndrome (CFS)

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  64. Hemispherx Biopharma Announces Patient Assistance Program for Chronic Fatigue Syndrome Open Label Study.

    Media Release
  65. Hemispherx Biopharma Form 10-K, March 2017. Internet-Doc 2017;.

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  66. Hemispherx Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees at Approved Clinical Sites in Nevada and North Carolina.

    Media Release
  67. Hemispherx Outlines Ampligen Combination Therapy Clinical Study Strategy for the Treatment of Multiple Cancers in Letter to Stockholders.

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  68. Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

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  69. AIM ImmunoTech Announces Availability of the ME/CFS Clinical Trial of its Drug Ampligen for Enrollment to COVID-19 Long Haulers.

    Media Release
  70. AIM ImmunoTech Announces IRB Approval to Enroll COVID-19 Long Haulers in the AMP-511 ME/CFS Clinical Trial of Ampligen.

    Media Release
  71. AIM ImmunoTech Announces First COVID-19-Induced Chronic Fatigue Long Hauler Patient Dosed with Ampligen.

    Media Release
  72. AIM ImmunoTech Provides Third Quarter 2021 Business Update.

    Media Release
  73. AIM ImmunoTech to Participate in a Solve M.E. Signature Event: Long COVID: Research, Policy, and Economic Impact on May 19, 2022.

    Media Release
  74. AIM ImmunoTech Provides Update on Ampligen Long COVID Development Program.

    Media Release
  75. A Multi-center, Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of Poly I:Poly C12U (Ampligen) 400 mg IV Twice Weekly Versus Placebo in Patients With Severely Debilitating Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME)

    ctiprofile
  76. Hemispherx Biopharma Announces Phase 3 Chronic Fatigue Syndrome Trial Meets Primary Endpoint.

    Media Release
  77. Hemispherx Biopharma Research Team Identifies Characteristics of Chronic Fatigue Syndrome (CFS) Patients Potentially Predictive of Improved Response to Ampligen.

    Media Release
  78. Hemispherx Biopharma Files New Drug Application for Ampligen as Treatment for Chronic Fatigue Syndrome.

    Media Release
  79. AIM ImmunoTech Announces Central IRB Approval of Phase 2 Study Protocol Evaluating Ampligen(Rm) for the Treatment of Post-COVID Conditions.

    Media Release
  80. A Phase II Study of Type-1 Polarized Dendritic Cell (aDC1) -Based Treatment in Combination With Tumor-Selective Chemokine Modulation (CKM: Interferon Alpha 2b, Rintatolimod and Celecoxib) in Melanoma Patients With Primary PD-1/PD-L1 Resistance

    ctiprofile
  81. AIM ImmunoTech and Study Collaborator Roswell Park Commence Enrollment in an NCI-funded Phase 2 Clinical Trial Evaluating Ampligen(Rm) (rintatolimod) in Primary PD-1/PD-L1 Resistant Melanoma.

    Media Release
  82. Hemispherx Biopharma Reviews Ampligen(R) Data With National Institute of Neurological Disorders and Stroke (NINDS).

    Media Release
  83. A phase II study of Ampligen (rintatolimod) for the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

    ctiprofile
  84. Hemispherx Updates Stockholders, Highlighting Ampligens Role in Enhancing Immunotherapeutic Therapies.

    Media Release
  85. Hemispherx Announces Data Presentation on the Potential for Ampligen to Improve Cancer Outcomes with Checkpoint Inhibitors.

    Media Release
  86. Hemispherx Announces Presentation of New-Found Properties of Ampligen at Immuno-Oncology Frontiers Conference, Jan 24.

    Media Release
  87. Hemispherx Biopharma Reports Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Disease Symptoms.

    Media Release
  88. Low Natural Killer (NK) Activity Observed Across the Chronic Fatigue Syndrome (CFS) Disease Spectrum.

    Media Release
  89. New Report Illuminates Ampligen(Rm)'s Unique Mechanism of Action.

    Media Release
  90. Hemispherx Announces Initial Test Results in Biosecurity/Biodefense Arena.

    Media Release
  91. A Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ampligen® in Patients With Post-COVID Conditions

    ctiprofile
  92. AIM ImmunoTech Announces FDA Clearance of IND Application to Evaluate Ampligen(R) in Phase 2 Clinical Study for the Treatment of Post-COVID Conditions.

    Media Release
  93. AIM ImmunoTech Enrolls and Doses First Subject in Phase 2 Study Evaluating Ampligen(Rm) for the Treatment of Post-COVID Conditions.

    Media Release
  94. AIM ImmunoTech Announces Completion of Enrollment in Phase 2 Study Evaluating Ampligen(Rm) for the Treatment of Post-COVID Conditions.

    Media Release
  95. AIM ImmunoTech Completes Treatment of Last Subject in Phase 2 Study Evaluating Ampligen(Rm) for the Treatment of Post-COVID Conditions.

    Media Release
  96. AIM ImmunoTech Reports Positive Topline Results from Phase 2 Study Evaluating Ampligen(Rm) for the Treatment of Post-COVID Conditions.

    Media Release
  97. AIM ImmunoTech Submits Pre-IND Application to the FDA for Phase 2 Clinical Studies of Ampligen as a Potential Early-Onset Therapeutic for COVID-19.

    Media Release
  98. A Phase I, Randomized, Double-Blind, Placebo-controlled, Placebo-Controlled Study to Evaluate the Safety and Activity of Repeated Intranasal Administration of Ampligen® (Poly I:Poly C12U) in Healthy Subjects

    ctiprofile
  99. AIM ImmunoTech Announces Two Year Extension of Agreement with Shenzhen Smoore Technology Limited to Develop and Test a New Inhalation Delivery Device for Ampligen.

    Media Release
  100. AIM ImmunoTech Submits Pre-IND Application to the FDA for Phase 2 Clinical Study of Ampligen as a Potential Infusion Therapy for Post-COVID-19 Cognitive Dysfunction.

    Media Release
  101. Institutional Review Board Authorizes Public Notification for Potential Enrollment of Subjects.

    Media Release
  102. Phase 1/2A Study of Rintatolimod and IFN Alpha Regimen in Cancer Patients With COVID-19

    ctiprofile
  103. AIM ImmunoTech Highlights Start of Recruitment in Roswell Park Clinical Trial Incorporating Ampligen in the Treatment of Cancer Patients with Mild or Moderate COVID-19.

    Media Release
  104. AIM ImmunoTech Announces FDA Authorization for First Human Ampligen Trial in COVID-19 Patients with Cancer; Provides Corporate Business Update for the First Quarter of 2020AIM ImmunoTech Announces FDA Authorization for First Human Ampligen Trial in COVID-19 Patients with Cancer; Provides Corporate Business Update for the First Quarter of 2020.

    Media Release
  105. AIM ImmunoTech Announces Addition of Single-Agent Ampligen Arm to Cancer Center's Ongoing Study in Cancer Patients with COVID-19.

    Media Release
  106. AIM Announces Milestone in COVID-19 Treatment and Prevention Efforts with First Patient Dosed in Study Evaluating Ampligen as Part of Combination Treatment for Patients with Cancer and COVID-19.

    Media Release
  107. AIM ImmunoTech Announces Addition of Single-Agent Ampligen Arm to Cancer Centers Ongoing Study in Cancer Patients with COVID-19.

    Media Release
  108. AIM ImmunoTech Completes All Treatments in Phase 1 Human Safety Study of Intranasal Administration of Ampligen.

    Media Release
  109. AIM ImmunoTech Announces First Healthy Subjects Dosed in Phase 1 Intranasal Ampligen Clinical Study.

    Media Release
  110. AIM ImmunoTech Announces Ethics Committee Approval to Commence Phase 1 Clinical Study of Ampligen as an Intranasal Therapy.

    Media Release
  111. AIM ImmunoTech Announces Positive Safety Data in First Cohort of Phase 1 Clinical Study Investigating Intranasal Administration of Ampligen as a Potential Prophylaxis or Treatment for COVID-19 and Other Respiratory Viral Diseases.

    Media Release
  112. AIM ImmunoTech Announces Positive Safety Data in Second Cohort of Phase 1 Clinical Study Investigating Intranasal Administration of Ampligen as a Potential Prophylaxis or Treatment for COVID-19 and Other Respiratory Viral Diseases.

    Media Release
  113. AIM ImmunoTech Announces Positive Safety Data from the Third Cohort of Its Phase 1 Intranasal Clinical Trial.

    Media Release
  114. AIM ImmunoTech Publishes Phase 1 Clinical Study Data Supporting the Safety of Ampligen as an Intranasal Therapy.

    Media Release
  115. AIM ImmunoTech Reports Positive Safety, Tolerability and Biological Activity Data for Intranasal Ampligen(Rm) (Rintatolimod) in Healthy Subjects.

    Media Release
  116. AIM ImmunoTech Provides Third Quarter 2020 Business Update.

    Media Release
  117. AIM ImmunoTech Announces Further Efforts to Establish Clinical Trials Assessing Ampligen as a Potential Protective and Early-Onset Treatment for the Current COVID-19 Pandemic.

    Media Release
  118. AIM ImmunoTech's Drug Ampligen to Be Tested by Japan's National Institute of Infectious Diseases as a Potential Treatment for the New SARS Coronavirus (SARS-CoV-2) Responsible for the New Human Infectious Disease COVID-19.

    Media Release
  119. AIM ImmunoTech Joins with ChinaGoAbroad for an Ampligen China Entry Against COVID-19, the New SARS-like Coronavirus Disease Epidemic.

    Media Release
  120. AIM ImmunoTech Files Three Provisional Patent Applications Surrounding Ampligen(R)for Use Against the SARS-like Wuhan 2019 Novel Coronavirus.

    Media Release
  121. AIM ImmunoTech Reports 2020 Year-End Financial Results.

    Media Release
  122. New Animal Model for Evaluating Antiviral Agents Against the SARS Virus Indicates Potential Effect of Ampligen(R), an Experimental Therapeutic.

    Media Release
  123. AIM ImmunoTechs Ampligen Featured in Peer-Reviewed Journal Cancers as a Potential Therapy for Cancer Patients with SARS-CoV-2.

    Media Release
  124. Rintatolimod Induces Antiviral Activities in Human Pancreatic Cancer Cells: Opening for an Anti-COVID-19 Opportunity in Cancer Patients? Internet-Doc 2021;.

    Available from: URL: https://www.mdpi.com/2072-6694/13/12/2896/htm
  125. Hemispherx Initiates Collaboration on SARS with Genome Institute of Singapore.

    Media Release
  126. SARS: Newly NIH Sponsored Studies of Potential Therapies for SARS Now Finds Hemispherx' Ampligen among the Most Active from a Large Pool of 70 -Seventy- Drug Candidates.

    Media Release
  127. Hemispherx Biopharma Expands SARS Prevention/Treatment Initiative; Prior to Anticipated Fall/Winter Outbreak also widens Distribution and Clinical Networks.

    Media Release
  128. AIM ImmunoTech Announces Publication of New Analysis of the Mechanism of Action of Ampligen as a Potential Prophylactic Therapy Against Ebola Virus Disease.

    Media Release
  129. AIM ImmunoTech Receives Orphan Drug Designation for Ampligen (rintatolimod) for the Treatment of Ebola Virus Disease.

    Media Release
  130. Hemispherx Biopharma Europe N.V./S.A. Receives Orphan Medicine Designation by the European Medicines Agency for Ampligen to Treat Patients With Ebola Virus Disease (EVD).

    Media Release
  131. Hemispherx Biopharma Europe N.V./S.A. Receives Positive Opinion on Application for Orphan Designation by the European Medicines Agency for Ampligen to Treat Patients With Ebola Virus Disease (EVD).

    Media Release
  132. Hemispherx Biopharma Posts USAMRIID Ebola Study Concluding Ampligen(Rm) Produced 100% Survival Rate in Rodents With 100% Mortality in Placebo.

    Media Release
  133. Hemispherx: U.S. Army Scientists (USAMRIID) Find Ampligen(R) Produces 100% Survival Rate in Ebola Virus Rodent Study.

    Media Release
  134. Hemispherx Biopharma and USAMRIID to Present New Discoveries Concerning the Efficacy of Ampligen(Rm) Against the Ebola Virus at Upcoming International Symposium on Filoviruses.

    Media Release
  135. Hemispherx Biopharma Announces Financial Results for the Nine Months Ended September 30, 2014.

    Media Release
  136. Hemispherx Biopharma and United States Army Medical Research Institute of Infectious Diseases (USAMRIID) Collaborate on Alferon(R) and Ampligen(R) Against the Ebola Virus.

    Media Release
  137. Hemispherx Announces Data Showing Inhibition of Ebola by Ampligen(Rm) Enlarged by Howard University Research.

    Media Release
  138. Ampligen(Rm) Blocks Critical Ebola Viral Disease (EVD) Protein Which is Linked to High Mortality in Man.

    Media Release
  139. Hemispherx Biopharma and United States Army Medical Research Institute of Infectious Diseases (USAMRIID) Agree to Collaborate in Studying Alferon(R) and Ampligen(R) Against the Ebola Virus.

    Media Release
  140. AIM ImmunoTech Announces Late-Breaking Presentation at the International Conference on Antiviral Research Regarding Ampligen as a Potential Therapy Against Ebola Virus Disease.

    Media Release
  141. Safety and Efficacy of Ampligen in the Treatment of HIV Patients Failing HAART

    ctiprofile
  142. The Role of Ampligen in Strategic Therapeutic Intervention (STI) of Highly Active Anti-Retroviral Therapy (HAART): A Multi-Center, Randomized, Controlled Study of Ampligen Potentiation of the HAART-Free Interval.

    ctiprofile
  143. Hemispherx Biopharma Initiates HIV/HEP-C Clinical Program; Clinical Trial with Ampligen in Collaboration with Esteve Laboratorios Targets HIV/HEP-C Twin Epidemics.

    Media Release
  144. Clinical Trials Insight: 700009615

    ctiprofile
  145. Hemispherx Biopharma Initiates Enrollment in HIV/HEP-C Clinical Program; Clinical Trial with Ampligen in Collaboration with Esteve Laboratorios Targets HIV/HEP-C Twin Epidemics.

    Media Release
  146. Hemispherx Files Positive Safety Report on Intranasal Use of Ampligen in Combination with FluMist Influenza Vaccine.

    Media Release
  147. Hemispherxs Ampligen Highlighted in Review of Role of TLR3 Agonist Support for Universal Flu Immunization Development Programs.

    Media Release
  148. Hemispherx Human Safety Study of Intranasal Ampligen(R) with Influenza Vaccine Shows Ampligen was Generally Well-Tolerated.

    Media Release
  149. Hemispherx Biopharma, Inc. to Webcast, Live, at VirtualInvestorConferences.com November 2.

    Media Release
  150. A Phase I/II, Two-Staged, Single-Center, Randomized, Double-Blind, Antibody Titer Study to Assess Immunogenicity and Safety of FluMist Intranasal Influenza Vaccine Administered With and Without a TLR-3 Agonist, Ampligen

    ctiprofile
  151. Clinical Trials Insight: 700056402

    ctiprofile
  152. Hemispherx Biopharma Prepares Application to Initiate Phase II Clinical Trials in China With Ampligen(R).

    Media Release
  153. Hemispherx Reports Successful Culmination of Three Year Joint Research Program at Japanese NIID.

    Media Release
  154. Hemispherx Biopharma Exploring Possible Research Programs in Zika Virus Modeled on a Prior Alferon(R)N Clinical Trial on Closely Related Flavivirus (West Nile).

    Media Release
  155. Hemispherx's Ampligen(R) Provides Anti-Tumor Activity Analogous to Emerging Immune Checkpoint Inhibitors.

    Media Release
  156. Hemispherx Updates Status of Immuno-Oncology Program in Pancreatic Cancer.

    Media Release
  157. A Phase IIa trial of Ampligen (rintatolimod) in combination with checkpoint inhibitors for the treatment of advanced urothelial cancer, renal cell carcinoma and Melanoma (Second line therapy or greater, combination therapy)

    ctiprofile
  158. Phase I/II study of rintatolimod to enhance the immune mediated effects of CPIs in patients with advanced solid tumors

    ctiprofile
  159. Hemispherx Biopharma and the University of Pittsburgh Collaborate on a Novel Chemokine-Modulatory Program for Cancer Immunotherapies With Ampligen(Rm) as a Key Component.

    Media Release
  160. AIM ImmunoTech Announces Report of Complete Topline Data from Roswell Park Comprehensive Cancer Center Study Evaluating Ampligen(Rm) as a Component of a Chemokine-Modulating (CKM) Regimen, with Paclitaxel, for the Treatment of Early-Stage Triple Negative Breast Cancer.

    Media Release
  161. Phase I Clinical Trial Assessing the Combination of Chemokine Modulation With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer

    ctiprofile
  162. AIM ImmunoTech Announces Progress Toward Opening of Breast Cancer Study at Roswell Park Comprehensive Cancer Center.

    Media Release
  163. AIM ImmunoTech Announces Presentation of New Data from Roswell Park Comprehensive Cancer Center Evaluating Ampligen(Rm) as a Component of a Chemokine-Modulating (CKM) Regimen, with Paclitaxel, for the Treatment of Early-Stage Triple Negative Breast Cancer.

    Media Release
  164. Gandhi S, Opyrchal M, Ford C, Slomba R, Attwood K, O'Connor T, et al. Preliminary indications of safety and efficacy of neoadjuvant chemotherapy plus chemokine-modulating regimen (rintatolimod, IFN-alpha2b, celecoxib) in triple negative breast cancer. SABCS-2022 2022; abstr. P4-06-07.

    Available from: URL: http://www.sabcs.org/
  165. AIM ImmunoTech Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Corporate Update.

    Media Release
  166. Hemispherx Issues 2019 Second Quarter Report Citing Strong Steady Progress in Cancer Clinical Trials.

    Media Release
  167. Hemispherx Announces Dutch Health Inspectorate Approval to Extend the Ampligen Pancreatic Cancer Early Access Program Until March 2020.

    Media Release
  168. Hemispherx Biopharma Announces IRB Approval of Clinical Study in Metastatic Triple Negative Breast Cancer in Collaboration with Roswell Park Comprehensive Cancer Center.

    Media Release
  169. Pilot Open Label Clinical Trial Evaluating the Safety and Efficacy of Chemokine Modulation to Enhance the Effectiveness of Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer

    ctiprofile
  170. Hemispherx Announces the First Participant Received Initial Dosing in Breast Cancer Clinical Trial Using Hemispherx' Ampligen and Pembrolizumab.

    Media Release
  171. AIM ImmunoTech Announces Positive Data from Phase 1 Study Evaluating Ampligen(Rm) for the Treatment of Stage 4 Metastatic Triple Negative Breast Cancer.

    Media Release
  172. Phase I-II Study of HER2 Vaccination With Poly(I) Poly(C12U) (Ampligen) as an Adjuvant in Optimally Treated Breast Cancer Patients

    ctiprofile
  173. Hemispherx Biopharma Announces Financial Results for the Three Months Ended September 30, 2011.

    Media Release
  174. A Phase IIa Study of Rintatolimod Plus Pembrolizumab in Refractory Metastatic Colorectal Cancer

    ctiprofile
  175. Phase 2a Study Evaluating a Chemokine-Modulatory Regimen in Patients With Colorectal Cancer Metastatic to the Liver

    ctiprofile
  176. AIM ImmunoTech Announces Positive Data from Phase 2a Study Evaluating Ampligen(Rm) as a Component of a Chemokine Modulatory (CKM) Regimen for the Treatment of Colorectal Cancer Metastatic to the Liver.

    Media Release
  177. Randomized Phase 1/2 Evaluation of Neoadjuvant Administration of a Chemokine-Modulatory Regimen in Patients With Recurrent Resectable Colorectal Cancer

    ctiprofile
  178. AIM ImmunoTechs Subsidiary Receives Orphan Medicinal Product Designation by the European Medicines Agency for Ampligen to Treat Pancreatic Cancer.

    Media Release
  179. AIM ImmunoTech Inc.s Drug Ampligen Awarded FDAs Orphan Drug Designation Status for the Treatment of Pancreatic Cancer.

    Media Release
  180. AIM ImmunoTech Submits IND and Accompanying Fast Track Application for Phase 2 Trial of Ampligen in Patients with Locally Advanced or Metastatic Late-Stage Pancreatic Cancer.

    Media Release
  181. A Phase 2, Randomized, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Ampligen Compared to Control Group / No Treatment Following FOLFIRINOX in Subjects With Locally Advanced Pancreatic Adenocarcinoma

    ctiprofile
  182. AIM ImmunoTech Announces Commencement of Phase 2 Study of Ampligen(R) for the Treatment of Pancreatic Cancer.

    Media Release
  183. AIM ImmunoTech Receives Erasmus Medical Center Ethics Board Authorization for Phase 2 Study of Ampligen(Rm) for the Treatment of Locally Advanced Pancreatic Cancer.

    Media Release
  184. AIM ImmunoTech Provides Progress on Advancement of Ampligen(Rm) Clinical Development Program for the Treatment of Pancreatic Cancer.

    Media Release
  185. AIM ImmunoTech Receives IND Clearance from the U.S. FDA to Advance its Phase 2 Study of Ampligen(Rm) for the Treatment of Locally Advanced Pancreatic Cancer.

    Media Release
  186. AIM ImmunoTech Provides Clinical Updates on Planned Phase 2 Study of Ampligen in Patients with Locally Advanced or Metastatic Late-Stage Pancreatic Cancer.

    Media Release
  187. AIM ImmunoTech Provides Second Quarter 2021 Business Update.

    Media Release
  188. AIM ImmunoTech Receives Statistically Significant Positive Survival Results in Pancreatic Cancer from Erasmus University Medical Center, Rotterdam, Netherlands.

    Media Release
  189. Early Access Program of Ampligen® (rintatolimod) in advanced and metastatic pancreatic cancer patients pre-treated with FOLFIRINOX

    ctiprofile
  190. AIM ImmunoTech Announces the Expansion of its Pancreatic Cancer Program to Include New Patients in the Netherlands.

    Media Release
  191. Hemispherx To Supply Ampligen for Pancreatic Cancer Patients in Canada Under Special Access Program.

    Media Release
  192. Hemispherx Releases Recently Manufactured Ampligen for Pancreatic Cancer Early Access Program in the Netherlands to Fill Stock Order.

    Media Release
  193. Hemispherx Biopharma Announces Significant Progress in its Ampligen Pancreatic Cancer Program and Multiple Ampligen+Checkpoint Blockade Immuno-Oncology Programs.

    Media Release
  194. Early Access Program of Rintatolimod in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Pancreatic Cancer

    ctiprofile
  195. Hemispherx Secures Corrections from Two Stock News Organizations Related to Their Inaccurate Reporting of an Equity Distribution Agreement Disclosed in a Recent SEC Filing.

    Media Release
  196. Hemispherx Biopharma Repurposes Ampligen in Immuno-Oncology.

    Media Release
  197. AIM ImmunoTech Announces Publication of Positive Data from Late-Stage Pancreatic Cancer Early Access Program (EAP) in the Cancers Special Issue: Combination and Innovative Therapies for Pancreatic Cancer.

    Media Release
  198. AIM ImmunoTech Announces Publication of Positive Findings from a Study Evaluating Ampligen(Rm) in the Treatment of Pancreatic Cancer in the Journal Clinical Cancer Research.

    Media Release
  199. Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab With TLR-3 Agonist Rintatolimod in Patients With Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy

    ctiprofile
  200. AIM ImmunoTech Announces First Subject Dosed in the Netherlands for Phase 1b/2 Study Evaluating Ampligen(Rm) (rintatolimod) in Combination with AstraZeneca's Imfinzi (durvalumab) for the Treatment of Pancreatic Cancer.

    Media Release
  201. AIM ImmunoTech Announces Abstract Accepted for Presentation at 15th Annual IHPBA World Congress.

    Media Release
  202. Jatwani K, Kalathil S, Slomba R, Farmer B, Attwood K, Roy AM, et al. A randomized phase II trial of neoadjuvant chemokine modulation in patients with localized prostate cancer undergoing radical prostatectomy. ASCO-GeCS-2024 2024; abstr. 340.

    Available from: URL: https://meetings.asco.org/abstracts-presentations/230387
  203. Randomized Phase 2 Study: Neoadjuvant Conditioning of Prostate Cancer Tumor Microenvironment Using a Novel Chemokine-Modulating Regimen

    ctiprofile
  204. A Phase 1/2 Trial Evaluating αDC1 Vaccines Combined With Tumor-Selective Chemokine Modulation as Adjuvant Therapy After Surgical Resection of Peritoneal Surface Malignancies

    ctiprofile
  205. A Phase I/II Randomized Clinical Trial of Autologous Oxidized Tumor Cell Lysate Vaccine For Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer

    ctiprofile
  206. Oregovomab and rintatolimod as adjuvant therapy for cancer

    ctiprofile
  207. Quest PharmaTech Announces Clinical Development Agreement with Hemispherx Biopharma Inc. to evaluate a combinatorial Immunotherapy Technology.

    Media Release
  208. Animal Model Data Presented at AACR Indicate That Hemispherx Biopharma's Ampligen(R) May be a Potent Tumor Vaccine Adjuvant.

    Media Release
  209. Hemispherx Biopharma Announces First Patient Treated in Phase 2 Ovarian Cancer Clinical Trial Evaluating Ampligen in Combination with Pembrolizumab and Cisplatin.

    Media Release
  210. Hemispherx Biopharma Announces Commencement of a New 45 Subject Clinical Trial Combining Ampligen and Mercks Keytruda in the Treatment of Recurrent Ovarian Cancer.

    Media Release
  211. Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer

    ctiprofile
  212. AIM ImmunoTech Announces Abstract from University of Pittsburgh Medical Center Accepted for Presentation at the AACR 2022 Annual Meeting.

    Media Release
  213. AIM ImmunoTech Announces Publication of Positive Results from Phase 1/2 Study of Intraperitoneal Chemo-Immunotherapy in Advanced Recurrent Ovarian Cancer.

    Media Release
  214. Hemispherx Reports Positive Safety and Survival Data in Phase 1 Stage 4 Ovarian Cancer Clinical Study Using Ampligen(Rm).

    Media Release
  215. Hemispherx Reports 2018 Third Quarter and First Nine Months Financial Results.

    Media Release
  216. A PHASE 1-2 NEOADJUVANT DOSE FINDING, SAFETY, AND IMMUNOLOGIC EFFICACY TRIAL OF INTENSIVE LOCOREGIONAL CHEMOIMMUNOTHERAPY FOR RECURRENT OVARIAN CANCER AND TUMOR-SPECIFIC INTRANODAL AUTOLOGOUS ALPHA-DC1 VACCINES

    ctiprofile
  217. BioFlorida Names AIM ImmunoTech CEO Thomas K. Equels as Entrepreneur of the Year.

    Media Release
  218. AIM ImmunoTech Provides Comprehensive Clinical Trials Update With Major Inflection Points Identified.

    Media Release
  219. AIM ImmunoTech Inc. Announces a Second DoD Award, This One of $8.3 Million, to Fund Phase 2 Clinical Trial to Study Ampligen as Part of a New Treatment for Brain-Metastatic Breast Cancer at the Moffitt Cancer Center.

    Media Release
  220. Hemispherx Biopharma, Inc. Announces $1 Million Registered Direct Offering.

    Media Release
  221. Hemispherx Biopharma, Inc. Announces $5 Million Registered Direct Offering.

    Media Release
  222. Hemispherx Biopharma Receives Therapeutic Discovery Project Grant From U.S. Department of Treasury.

    Media Release
  223. Hemispherx Biopharma Reaches Agreement with Avrio Biopharmaceuticals for the Accelerated Production of Ampligen(Rm).

    Media Release
  224. AIM ImmunoTech Bolsters Intellectual Property Estate for Ampligen(R) with Issuance of Two Key U.S. Patents.

    Media Release
  225. AIM ImmunoTech Reports Second Quarter Financial Results and Provides Clinical Pipeline Update.

    Media Release
  226. AIM ImmunoTech Broadens Patent Portfolio with New Netherlands Utility Patent Covering Ampligen(R) and Other AIM-Developed dsRNA Products to Include Rugged dsRNA for Use in COVID-19 Treatment or Prevention.

    Media Release
  227. AIM ImmunoTech Bolsters Intellectual Property Portfolio for Ampligen(Rm)with Issuance of New Netherlands Utility Patent Covering Ampligen(Rm)and other AIM Developed dsRNA Products for Use in COVID-19 Treatment or Prevention.

    Media Release
  228. AIM ImmunoTech Files Provisional Patent Application for Ampligen as an Early-Onset Intranasal Therapy that May Also Confer Enhanced Immunity to a Wide Range of Respiratory Viruses.

    Media Release
  229. AIM ImmunoTech Announces Filing of Provisional Patent Application for Use of Ampligen as Both an Intranasal and an IV Therapy for Post-COVID-19 Cognitive Dysfunction (PCCD).

    Media Release
  230. AIM ImmunoTech?s Ampligen Featured in Peer-Reviewed Journal Cancers as a Potential Therapy for Cancer Patients with SARS-CoV-2. Internet-Doc 2022;.

    Available from: URL: https://www.sec.gov/Archives/edgar/data/946644/000149315221014224/ex99-1.htm
  231. AIM ImmunoTech Files Provisional Patent Application for the Use of Ampligen(R) as a Potential Therapy for COVID-19 Induced Chronic Fatigue.

    Media Release
  232. HEMISPHERX BIOPHARMA 10-K. Internet-Doc 2019;.

    Available from: URL: https://www.sec.gov/Archives/edgar/data/946644/000149315219004583/form10-k.htm
  233. Hemispherx Biopharma Receives the European Patent Office Grant of New Composition of Matter Patent Covering Ampligen(R) Formulations.

    Media Release
  234. Hemispherx Receives the European Patent Office Examining Division's Notice of Intention to Grant the New Composition of Matter Patent Covering Ampligen(R) Formulations.

    Media Release
  235. Hemispherx Receives New U.S. Composition of Matter Patent Covering Ampligen(Rm) Formulations.

    Media Release
  236. Hemispherx Biopharma Receives U.S. Patent Office Notification of New Patent Granted for the Use of Ampligen(R) as an Influenza Virus Vaccine Adjuvant for Protection Against Pandemic Avian Influenza.

    Media Release
  237. AIM ImmunoTech Announces Authorizations from Competent Authority and Ethics Board in the Netherlands to Begin a Phase 1b/2 Study Evaluating Ampligen(Rm) (rintatolimod) in Combination with AstraZeneca's Imfinzi (durvalumab) for the Treatment of Pancreatic Cancer.

    Media Release
  238. AIM ImmunoTech Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update.

    Media Release
  239. AIM ImmunoTech Reports First Quarter 2022 Financial Results and Provides Corporate Update.

    Media Release
  240. Hemispherx Biopharma Issues Clinical Update for Ampligen Immuno-oncology Program.

    Media Release
  241. Hemispherx Biopharma Issues Letter to Stockholders.

    Media Release
  242. Hemispherx Encouraged by Cytokine Biomarker Discovery Which May Lead to a Diagnostic for Chronic Fatigue Syndrome.

    Media Release
  243. Hemispherx Biopharma to Present New Retrovirus (XMRV) Data at 1st International Workshop on XMRV and Chronic Fatigue Syndrome (CFS).

    Media Release
  244. Japanese NIH Research Reaffirms and Expands Pandemic Flu Protection by Ampligen(R).

    Media Release
  245. Hemispherx Presents Evidence of Ampligen (Rm) Synergies with Existing Antivirals at International Avian Influenza Conference.

    Media Release
  246. 3 New Studies Show Hemispherx Biopharma's Ampligen(R) and Alferon(R) LDO May Provide Defense against Avian Flu.

    Media Release
  247. Hemispherx Biopharma's Investigational Drug Increases Physical Performance in New Chronic Fatigue Syndrome -CFS- Clinical Study; Maximum Oxygen Consumption Increased 10-Fold with Ampligen-R- vs. Placebo.

    Media Release
  248. Hemispherx Biopharma Presents Newphase III Data on Ampligen at the 7th International Conference for Chronic Fatigue Syndrome.

    Media Release
  249. CARTER W, Strayer D, Mitchell W, Stevens S, AMP 516 Investigators. Phase III, randomized, double-blinded clinical trial in chronic fatigue syndrome shows significant improvement in exercise treadmill performance with ampligen compared to placebo. 17th-ICAR-Late 2004;13.

  250. Mitchell W, Blick G, Strayer D, CARTER W, AMP 720 Investigators, et al. A phase IIB prospective, randomized, controlled study evaluating AMPLIGEN during structured treatment interruption of HAART in HIV infection. Antiviral-Res 2003;5741.

  251. Hemispherx Presents New Data from Phase IIB Clinical Trial of RNA-based Ampligen(R) for Structured Treatment Interruption in HIV at DART Conference.

    Media Release
  252. Strayer D, Blick G, Mitchell W, Cimoch P, CARTER W. A phase IIB prospective, randomized, controlled study evaluating the immunomodulatory role of poly I:poly C12U against HIV. 14th-Aids-Suppl 2002;37.

  253. Hemispherx announces poly I: poly C12U increases the control of HIV during strategic treatment interruption in chronically HIV infected patients.

  254. Essey RJ, McDougall BR, Robinson WE. Mismatched double-stranded RNA (PolyI-polyC(12)U) is synergistic with multiple anti-HIV drugs and is active against drug-sensitive and drug-resistant HIV-1 in vitro. Antiviral-Res 2001;51189-202.

    PubMed | CrossRef Fulltext
  255. New study indicates benefits of Ampligen (R) in treatment of severe CFS.

  256. Ijichi K, Mitamura K, Ida S, et al. Comparison of antiviral effects of mismatched double-stranden RNA and 1-(2'deoxy-2'-fluoro-beta-D-arabinofuranosyl) -5-methyl-uracil (D-FAMU) against duck hepatitis B virus in vitro. Antiviral-Chem-Chemother 1997;8537-540.

    PubMed | CrossRef Fulltext
  257. Thompson KA, Strayer DR, Salvato PD, Thompson CE, Klimas N, et al. Results of a double-blind placebo-controlled study of the double-stranded RNA drug polyI:polyC(12)U in the treatment of HIV infection. Eur-J-Clin-Microbiol-Infect-Dis 1996;15580-587.

    PubMed | CrossRef Fulltext
  258. Buzaid AC, Strayer DR, Witman PA, et al. Phase I/II study of poly I:polyC(12)U (Ampligen Rm) shows activity against metastatic melanoma. 30th-ASCO 1994;13399.

    PubMed
  259. O'Marro SD, Armstrong JA, Asuncion C, Gueverra L, Ho M. The effect of combinations of ampligen and zidovudine or dideoxyinosine against human immunodeficiency viruses in vitro. Antiviral-Res 1992;17169-177.

    PubMed
  260. Hendrix CW, Margolick JB, Petty BG, Markham RB, Nerhood L, et al. Biologic effects after a single dose of poly(I):poly(C12U) in healthy volunteers. Antimicrob-Agents-Chemother 1993;37429-435.

    PubMed
  261. Carter WA, Ventura D, Shapiro DE, Strayer DR, Gillespie DH, et al. Mismatched double-stranded RNA, Ampligen (poly(I) : poly(C12U), demonstrates antiviral and immunostimulatory activities in HIV disease. Int-J-Immunopharmacol 1991;13 (Suppl. 1)69-76.

  262. Konishi K, Mukoyama A, Muller WEG, et al. Effect of poly(I) . poly(C12U) (Ampligen) on enteric virus (rotavirus, poliovirus and Coxsackie B3 virus) infections. Lett-Appl-Microbiol 1994;19386-390.

    PubMed
  263. Belgium Clinical Trial Demonstrates that Ampligen(R) is Effective in the Treatment of Chronic Fatigue Syndrome.

    Media Release
  264. Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, et al. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin-Infect-Dis 1994;18 (Suppl.1)96-104.

  265. McMahon D, Winkelstein A, Huang X-L, Armstrong J, Pazin G, et al. Acute reactions associated with the infusion of ampligen. AIDS 1992;6235-236.

    PubMed
  266. Niu J, Wang Y, Dixon R, et al. The use of ampligen alone and in combination with ganciclovir and coumermycin A1 for the treatment of ducks congenitally-infected with duck hepatitis B virus. Antiviral-Res 1993;21155-171.

    PubMed
  267. Belgian study reports good results, trial is expanded.

    Media Release
  268. Strayer DR, Carter WA, Brodsky I, et al. A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome. Clin-Infect-Dis 1994;18 (Suppl.1)88-95.

  269. O'Brien CB, Garcia G, Henzel B, et al. Ampligen treatment of chronic hepatitis B. Gastroenterology 1994;106 (Suppl.)952.

  270. Armstrong JA, McMahon D, Huang X-L, Pazin GJ, Gupta P, et al. A phase I study of ampligen in human immunodeficiency virus-infected subjects. J-Infect-Dis 1992;166717-722.

    PubMed
  271. Gillespie D, Hubbell HR, Carter WA, Midgette P, Elsasser W, et al. Synergistic inhibition of AZT-resistant HIV by AZT combined with poly(I):poly(C12U), without synergistic toxicity to bone marrow progenitor cell elements. In-Vivo 1994;8375-381.

    PubMed
  272. Ushijima H, Tsiapalis CM, Daum T, Schroder HC, Matthes E, et al. Synergistic anti-human immunodeficiency viral (HIV-1) effect of the immunomodulator ampligen (mismatched double-stranded RNA) with inhibitors of reverse transcriptase and HIV-1 regulatory proteins. Antiviral-Chem-Chemother 1993;4(6):315-321.

    PubMed
  273. Ablashi DV, Berneman Z, Strayer DR, et al. Poly(I).poly(C12U) inhibits in vitro replication of human herpesvirus type 6. Clin-Infect-Dis 1994;18 (Suppl.1)113.

  274. Ablashi DV, Berneman ZN, Williams M, Strayer DR, Kramarsky B, et al. Ampligen inhibits human herpesvirus-6 in vitro. In-Vivo 1994;8587-591.

    PubMed
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