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Interferon alpha n3 - AIM ImmunoTech

Drug Profile

Interferon alpha n3 - AIM ImmunoTech

Alternative Names: Alferon LDO; Alferon LDO (Low Dose Oral); Alferon N; Alferon N Gel; Alferon N Injection; Alferon N LDO; alpha-n3-IF; Altemol; Interferon alfa-N3; Interferon alfa-n3 human leukocyte derived (Alferon N Injection); Interferon-α-n3; Leukocyte interferon; Naturaferon; Natural alpha interferon

Latest Information Update: 28 Feb 2021

At a glance

  • Originator Stem Cell Innovations
  • Developer AIM ImmunoTech; Fujimoto Pharmaceutical; Howard University; National Institute of Allergy and Infectious Diseases; Swiss Department of Defence, Civil Protection and Sport; United States Army Medical Research Institute of Infectious Diseases
  • Class Anti-inflammatories; Antivirals; Interferons
  • Mechanism of Action Immunostimulants
  • Orphan Drug Status

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

    Yes - Middle East respiratory syndrome coronavirus
  • New Molecular Entity Yes

Highest Development Phases

  • Marketed Human papillomavirus infections
  • Registered Hepatitis C; Inflammation; Multiple sclerosis; Viral infections
  • No development reported Ebola virus infections; HIV infections; Influenza A virus H7N9 subtype; Influenza A virus infections; Influenza virus infections; Middle East respiratory syndrome coronavirus; Venezuelan equine encephalomyelitis; West Nile virus infections; Zika virus infection
  • Discontinued Kaposi's sarcoma; Small cell lung cancer

Most Recent Events

  • 28 Feb 2021 No recent reports of development identified for preclinical development in Zika-virus-infection in USA (PO)
  • 23 Aug 2019 Hemispherx Biopharma is now called AIM ImmunoTech
  • 08 Feb 2019 9259972: No updates

Development Overview

Introduction

Interferon α n3 is a natural interferon originally produced by Interferon Sciences (later Stem Cell Innovations), and later acquired by Hemispherx (now AIM ImmunoTech), from pooled units of human leukocytes which have been induced by incomplete infection with the avian Sendai virus. Interferon-α-n3 enhances various components of the immune response and activates cytotoxic cells via the direct action on a number of interferon-responsive cells in the immune system. Additionally, interferon-α-n3 works through cellular "molecular cascades" and therefore is not vulnerable to mutational changes [1] .

An injectable form of interferon-α-n3 (Alferon N Injection®) has been approved and marketed as an intralesional treatment in the US for refractory or recurring external genial warts due to human papillomavirus (HPV) infections in adult patients (18 years of age or older). In Argentina, the product has been approved for use in any patient who has failed or become intolerant to treatment with recombinant interferon in patients with chronic active hepatitis C infection, HPV infections, inflammation, multiple sclerosis and viral infections;

Phase I development is underway for influenza virus infections in the US. Preclinical development is underway for Zika virus infections, and early research development is ongoing, in the US to assess the potential of interferon-α-n3 as a bio-defence agent including Ebola virus infections, Middle East respiratory syndrome coronavirus, alphavirus infections.

Phase II development for Kaposi's sarcoma and small cell lung cancer has been discontinued; No recent reports of development have been identified for Hepatitis C in Japan, Mexico and the US, HIV infections in the US, influenza virus infections in India, HPV infections (PO) in USA and Hong Kong and West Nile virus infections in the US.

The product appeared to be launched in Mexico as Altemol® for anogenital warts, however, its marketing was not active or appears to be discontinued.

As at November 2017, no recent reports of development had been identified for phase-I development in Influenza-virus-infections in USA (PO), preclinical development in Influenza-A virus H7N9 subtype in USA (SC), preclinical development in Influenza-A-virus-infections (Prevention) in USA (SC, Injection), Canada (SC, Injection), USA (PO), Canada (PO), research development in Alphavirus Infections in USA (SC), research development in Middle-East-respiratory-syndrome-coronavirus in USA (SC).

As at June 2018, no recent reports of development had been identified for preclinical development in Influenza-A virus H7N9 subtype in Switzerland (SC).

As at October 2018, no recent reports of development had been identified for research development in Ebola-virus-infections in USA (PO).

In August 2019, Hemispherx Biopharma changed its name to AIM ImmunoTech [2] .

As at February 2021, no recent reports of development had been identified for preclinical development in Zika-virus-infection in USA (PO).

Company Agreements

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 Alferon® [3] .

In April 2016, Hemispherx Biopharma and Scientific Products Pharmaceutical (SCIEN) entered into a clinical trial, sales, marketing, distribution, and supply agreement for Middle Eastern countries, including Saudi Arabia, United Arab Emirates, Kuwait, Oman, Qatar, and Bahrain. Pursuant to the agreement, SCIEN will purchase certain quantities of clinical grade interferon-α-n3 for investigative use in individuals who are exposed to and show early onset symptoms of the coronavirus that causes MERS [4] .

In August 2015, Hemispherx and Emerge Health entered into a collaboration agreement to seek regulatory approval in Australia and New Zealand, and commercialise interferon-alpha-n3 for human papillomavirus infections under a named patient programme. Under the terms of the agreement, Emerge received an exclusive marketing license to the product that will be supplied by Hemispherx at a predetermined transfer price [5] .

In March 2003, Hemispherx announced that it had acquired certain assets from Interferon Sciences (later Stem Cell Innovations), including limited rights to the approved product Alferon N Injection®. Under the terms of the acquisition, Hemispherx also acquired the rights to Interferon Science's experimental α-interferon products Alferon N Gel® and Alferon N LDO® as well as an FDA approved biological production facility located in New Brunswick, New Jersey. Hemispherx also received all Interferon Science's interferon-related patents, licences, clinical data and forward revenues. Interferon Sciences was to receive Hemispherx common stock in the amount of $US1 350 000 and an additional 125 000 shares [6] . Subsequently, in March 2004, Hemispherx completed the acquisition of all the worldwide rights on Alferon N® as well the US FDA approved biological production facility [7] . The remaining royalty interest on the sales of natural interferon-α-n3 products was purchased by Hemispherx from Interferon Sciences in August 2006 [8] .

Hemispherx licensed interferon-α-n3 injection to GP Pharm Latino America (an affiliate of GP Pharm SA) in Latin America in December 2010. Under the terms of the agreement, Hemispherx will manufacture and supply the product to GP Pharm in Argentina under an exclusive sales, marketing, distribution and supply agreement. GP Pharm will be responsible for gaining regulatory approval for each indication and commercialising Alferon N Injection® in Argentina. Based upon achieving regulatory approval and certain first sale performance milestones, GP Pharm has the right to expand its territory to include other Latin American countries [9] . In 2012, under the terms of the agreement, Alferon’s indication in Argentina was extended to treat any disease that is refractory to recombinant interferon. The original agreement between Hemispherx and GP Pharm expired in June 2015 and was renewed in May 2016 with the same clauses as earlier [10] .

In July 2014, Hemispherx executed an agreement with Bioclones for seeking approval of the Government of South Africa to commence a trial of interferon-α-n3 (Alferon N®) in HIV-1 infected patients, for both suppression of replication and reduction of latent HIV. Both the companies will co-sponsor the trial, which is a part of a broad strategic alliance. Bioclones, a global partner to AIM ImmunoTech, will represent AIM ImmunoTech in South Africa and will conduct the trials in the country [11] .

The US National Institute of Allergy and Infectious Diseases (NIAID) is collaborating with AIM ImmunoTech for the biodefense indications [12] .
AIM ImmunoTech is also collaborating with the Swiss Department of Defense, Civil Protection and Sports to evaluate interferon-α-n3 against oseltamivir-resistant H7N9 influenza virus strains, 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 [13] . In September 2014, the collaborative agreement was expanded to include a study that would evaluate interferon-α-n3 against the Ebola virus infections [14] . 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. Interferon-α-n3 has shown potential value with respect to inclusion in several therapeutic cocktails under development for Ebola [15] .

Hemispherx also formed an alliance with Max Neeman International, a Clinical Research Organisation in India, for interferon-α-n3 injection to treat seriously ill patients hospitalised with seasonal or pandemic influenza in India.

Andromaco was responsible for the distribution of injectable interferon-α-n3 in Mexico.

Supply agreement

In August 2015, Hemispherx entered into a contract with Gulf Coast Regional Blood Center, whereby the latter will supply leukocytes for the manufacture of interferon-α-n3. Hemispherx entered into the contract, following termination of its long-term contract with BioLife d/b/a Penn Plasma for supply of blood. The contract was terminated because BioLife d/b/a Penn Plasma decided to shut down its Penn Plasma business arm [16] .

Discontinued agreements

In September 2003, Hemispherx Biopharma, Incorporated reported that it had signed an agreement with Guangdong Medicine Group Corporation to organise clinical trials, marketing, sales and distribution for both of its lead compounds, interferon-α-n3 and Ampligen® [see RDI profile 800001203], in the People's Republic of China. The agreement stipulates that the Guangdong Medicine Group Corporation (GMC) will conduct clinical trials with Alferon N Injection® for the treatment of HCV. All costs related to the trials are to be covered by GMC. Additionally, GMC has to develop and implement marketing and promotional programmes [17] . However, this company is no longer listed as a partner on the Hemispherx website.

Hemispherx reported in August 2003 that it entered into a sales and marketing agreement with Engitech to launch interferon-α-n3 on a nationwide scale [18] . However, it appears that this agreement is no longer active.

Both the injectable and gel formulations of interferon-α-n3 were licensed to Fujimoto Pharmaceuticals for development and marketing in Japan. Distribution agreements for interferon-α-n3 were also made with Edward Keller Limited in Hong Kong and Cell Pharm in Germany but it appears that these agreements were discontinued.

Key Development Milestones

Biodefence/biosecurity indications

In November 2014, Hemispherx Biopharma and United States Army Medical Research Institute of Infectious Disease (USAMRIID) reported that interferon-α-n3 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 interferon α n3 and rintalimod [see RDI Profile 800001203]. These studies are being planned to establish a basis for clinical interventions in both preventative and therapeutic settings of Ebola virus disease [19] . In September 2014, Hemispherx Biopharma collaborated with researchers from the USAMRIID to assess rintalimod and interferon-α-n3 as a treatment for Ebola virus infections [20] .

AIM ImmunoTech is undertaking major programmes to investigate interferon α n3 as a biodefence agent, with a focus on the prevention or treatment of H7N9 pandemic influenza virus infections, α virus infections including Venezuelan Equine Encephalomyelitis (VEE), and Middle East Respiratory Syndrome (MERS). Data from in vitro studies demonstrated that interferon-α-n3 was highly active against oseltamivir-resistant strains of H7N9 pandemic influenza, and the product has also been shown to be highly active against the other two virus classes of interest. Interferon-α-n3 has also showed inhibition of neuromidase resistant Shanghai/1/H7N9 virus. More recently, Hemispherx reported that research conducted by the NIAID demonstrated that interferon-α-n3 inhibits the replication of MERS coronavirus infection in vitro. The findings were confirmed by studies conducted at the University of Texas Medical Branch [21] [12] [22] [23] .

Hepatitis C virus (HCV) infections

Interferon α n3, under the brand name Naturaferon®, is approved in Argentina for the treatment of Hepatitis C infections in treatment-experienced patients who fail or become intolerant to recombinant interferon [24] [25] [26] .

Phase III trials of interferon α n3, or Alferon N® Injection, have been completed in the US and Mexico for the treatment of previously untreated patients with chronic active hepatitis C. A total of 275 patients were treated with interferon-α-n3 for 24 weeks with a further 24 weeks follow-up. After completing the analysis of the results, Interferon Sciences had intended to request a meeting with the FDA to determine the adequacy of the data for filing purposes. However, following the acquisition of the rights to interferon-α-n3 by Hemispherx, the compound appeared to be in phase II/III development with the latter company for hepatitis C. Fujimoto was conducting phase II clinical studies in Japan for hepatitis C. However, no further development has been reported in the US or Japan for this indication. AIM ImmunoTech plans to conduct a phase III study of Alferon N® Injection in hepatitis in China.

HIV infections

Hemispherx and Bioclones intend to initiate a clinical trial in South Africa to assess the safety and biological effects of adding interferon α n3 to a strategic therapeutic intervention protocol. The trial will enrol approximately 30 patients with HIV [11] [27] .

In March 2004, Hemispherx announced that the US FDA had authorised an IND that enabled the company to initiate a phase II study of Alferon N LDO®, Low Dose Oral natural interferon, in asymptomatic HIV positive patients (NCT00215852). The study was an open-label, dose ranging, outpatient study involving approximately 60 patients who were randomly assigned to each dose level. Patients were administered the assigned Alferon N LDO® dose once each day for 10 consecutive days; the overall duration of the study was 6 weeks. The primary endpoints of the trial were an increase or upregulation in genes known to be mediators of the natural immune response and secondary endpoints included the absolute CD4 count and plasma HIV RNA levels. No recent development on this study has been reported [28] [29] .

Interferon Sciences previously completed a phase III study of interferon α n3 in 110 HIV-infected patients with CD4 counts ≥250 cells/mm3 and viral loads ≥2000 copies/ml. As the study's primary efficacy variable, reduction in viral load, was not achieved at the end of treatment, the FDA indicated that another trial was necessary to further evaluate the efficacy of interferon-α-n3 injection for this indication.

Human papillomavirus (HPV) infections

An injectable form of interferon α n3, Alferon N Injection® or Altemol®, was marketed in the USA and Mexico for the treatment of genital warts caused by HPV. However, in Mexico its marketing was not active or discontinued. The commercial sales of Alferon N Injection® were halted in March 2008 for reasons relating to the expiration date of the company's finished goods inventory and the need to prepare the company's manufacturing facility for the FDA pre-approval inspection regarding the NDA for Ampligen® [see Adis Insight Drug profile 800001203] (Hemispherx Biopharma Form 10-K, March 2010). The company reported that it was undertaking a major capital improvement programme to upgrade its manufacturing capability, and according to the its website, the product was being marketed in the US in October 2012. In November 2014, Hemispherx reported that it has received a Certificate of Approval from the city of New Brunswick for the work completed to upgrade its manufacturing facility. The company will test the scaled up facility to produce commercial levels of Alferon N Injection®, Alferon N LDO® [see below] and other products [25] . The facility commenced its operations at the beginning of 2015. The FDA will reaffirm the amended BLA for Alferon N Injection® before the commercial sales of the product anticipated by late 2015. FDA's approval will be required to release the commercial product following the submission of stability and quality release data. Amada Healthcare will distribute the product [30] [31] .

In August 2015, Hemispherx announced that in an analysis of relapsed and refractory neutralising antibody (NAB) positive patients who switched treatment to interferon α n3 injection, restoration in the clinical response was found to be in 33/40 (82%) of patients [32] .

Interferon-α-n3 injection was approved in Argentina for the treatment of patients with refractory or recurring HPV, in January 2012. GP Pharm submitted the application for the approval of interferon-α-n3 injection for the treatment of HPV infections in August 2011. In March 2013, the regulatory authorities in Argentina expanded the label for the product to include the treatment of patients that have failed treatment with or become intolerant to recombinant interferon, while receiving treatment for any disease, including multiple sclerosis, hepatitis C, and certain cancers. Hemispherx had applied for an extension of the label, in October 2012, to include patients with hepatitis C who had developed neutralising antibodies to recombinant interferon. The company is awaiting approval from the US FDA for the sale of its existing inventory, and product that is to be manufactured at its facility in New Brunswick, before commencing commercial launch in this market. Alferon N Injection® is being marketed in Argentina under the brand name Naturaferon® [33] [34] [35] [36] .

Hemispherx conducted clinical trials of Alferon N LDO® in patients with HPV infections in the US and Hong Kong [37] . Interferon Sciences conducted phase II clinical trials in the US with the gel formulation of interferon-α-n3 (Alferon N Gel®) in women with intravaginal warts caused by human papillomavirus (HPV) who have recurrent, persistent low or high grade cervical dysplasia. However, no recent reports on development of both formulations of interferon-α-n3 identified for this indication.

Influenza virus infections (including influenza A virus infections [pandemic or avian influenza])

In January 2014, Hemispherx reported that the administration of a low dose oral formulation of interferon-α-n3 (Alferon® LDO) in a primate model provided protection from pulmonary tissue damage associated with infection by highly pathogenic avian influenza virus (H5N1) [38] . In September 2014, company released positive data on Alferon® LDO in prevention of viral infection caused by H5N1 in non-human primate model [39] .

A preclinical programme to investigate interferon-α-n3 for oseltamivir (Tamiflu®)-resistant influenza A H7N9 virus strains in Switzerland was announced in May 2014 [see Adis Insight Drug profile 800007569] [13] .

Hemispherx Biopharma stated that preclinical studies of Alferon N Injection®/Alferon LDO® were underway in the US and Canada for avian influenza. Company researchers have indicated that these products may be promising in the treatment of oseltamivir-resistant influenza A virus H7N9 infections in both animals and humans [40] [41] . Phase II trials of Alferon LDO® for the prevention and treatment of influenza are in the preparation stage (Hemispherx's pipeline, March 2015). The US FDA authorised the protocol for a randomised, double-blind, placebo-controlled, dose-ranging phase II trial of Alferon® LDO for the prophylaxis and treatment of seasonal influenza in more than 200 subjects.

In April 2010, Hemispherx Biopharma and the Indian clinical research organisation (CRO) Max Neeman International announced a collaborative research effort for interferon-α-n3 for influenza virus infections. The partnership aimed to improve the treatment of seriously ill patients hospitalised with either seasonal influenza or pandemic influenza (influenza A virus infections). Approval from the Indian Drugs Controller General for this phase II trial (CTRI/2010/091/001115; study ALFN 101) was granted on 13 July 2010, with enrolment commencing immediately, intending to coincide with the Indian monsoon season (July to mid-October; peak in August) [42] [43] [44] . Only 25 out of 60 patients completed the study across eight investigative sites. Hence, in June 2012, the trial was suspended due to slow enrolment and interim analysis of results on 30 out of 60 planned patients was pending (Hemispherx Form 10-K, March 2012). Subsequently, due to delayed interim analysis and reduced resources, the trial was discontinued (Hemispherx Form 10-K, March 2014). Furthermore, no recent reports on development for this indication in India identified.

Hemispherx Biopharma was planning trials of Alferon N Injection® in seriously ill, hospitalised patients with influenza in Argentina (Hemispherx Biopharma annual report, February 2011).

In January 2011, the FDA lifted the clinical hold on Hemispherx's planned phase II clinical trial in the US investigating SC interferon α n3 in patients with influenza. The hold was lifted following review of a complete response to the agency submitted in November 2010. The proposed randomised trial will involve approximately 200 subjects and will evaluate the prophylaxis and treatment of seasonal and pandemic influenza. The study has been delayed as the company intended to conduct a confirmatory study using gene expression methods to identify the systemic gene activation effects in peripheral blood leukocytes following treatment with interferon α n3 (Hemispherx Form 10-K, March 2012).

Hemispherx Biopharma has received FDA-approval to conduct a well-controlled phase II trial investigating the efficacy and tolerability of low-dose oral interferon α-n3 (Alferon® LDO) for the prevention and treatment of influenza in a family setting [45] [46] .

Early-stage clinical trials of Alferon® LDO were conducted by Hemispherx Biopharma in the influenza indication. A clinical trial in healthy volunteers to investigate whether the agent could resuscitate broad-spectrum antiviral and immunostimulatory genes was delayed because of funding issues. However, the study has recommenced (Hemispherx Biopharma Form 10-K, March 2010).

In November 2005, Hemispherx Biopharma entered into an agreement with Defence R&D Canada, an agency of the Canadian Department of National Defence, to investigate the antiviral efficacy of interferon-α-n3 in human respiratory influenza virus infections in validated animal models [47] .

Preclinical studies, conducted in collaboration with ViroClinics, have indicated that Alferon LDO® may have potential in the treatment of seasonal influenza pandemics. Hemispherx was planning to conduct clinical trials in this indication [48] .

Alferon® LDO has been shown to reduce the severity of pathology resulting from infection of macaques by a highly pathogenic strain of avian influenza. Hemispherx has been hoping that Alferon® LDO can receive expedited review and emergency-based approval as an anti-HPAI (highly pathogenic avian influenza) agent, solely relying on the 'animal rule' for demonstration of efficacy. This is where marketing approval can be granted based on efficacy in relevant animal models with only phase I safety trials required in humans [49] .

Middle East Respiratory syndrome (MERS)

In January 2016, Hemispherx reported that the European Medicines Agency has granted orphan drug designation to Alferon N Injection® for the treatment of MERS. The EMA's decision was based on the positive opinion given by the Committee for Orphan Medicinal Products (COMP) [50] [51] . Research conducted using human cells in culture suggested that the agent may be effective either as a preventative and/or treatment of early MERS infection [52] .

Multiple sclerosis

In June 2004, Hemispherx commenced a multiple sclerosis salvage programme. As part of the programme, the company was to conduct a multicentre, open-label, phase IIb trial evaluating the safety and efficacy of injectable interferon-α-n3 in patients with multiple sclerosis who have discontinued current treatments (Avonex®, Rebif® or Betaseron®) because of clinical progression, intolerance or formation of neutralising antibodies. The primary endpoints included the annual clinical relapse rate at baseline compared with week 48. Hemispherx received FDA approval for this trial in July 2004, but the trial had not been initiated by late 2012. However, according to the Hemispherx pipeline, the company is still intending to conduct a phase II trial in this indication in the US [53] [54] .

Severe Acute Respiratory Syndrome (SARS)

Multiple collaborations with non-commercial organisations have been conducted in this indication. However, while the therapy may have potential in this indication it appears that commercial development is not underway.

In May 2003, Hemispherx announced that, in response to an urgent request from the Singapore government, it was initiating a collaboration with the Genome Institute of Singapore (GIS), to evaluate Alferon® N and Ampligen® [see Adis Insight Drug profile 800001203] for the potential treatment of SARS [55] . Results of an independent study conducted at the GIS and published in April 2004, showed that Alferon® N has superior antiviral activity in an in vitro model of SARS-CoV, when tested among 19 other clinically approved compounds from several major antiviral pharmacological classes [56] .

In June 2003, at the Anti-SARS Forum, held at the University of Pennsylvania, Hemispherx presented data from a comparative safety study of Alferon® N and Intron® A [see Adis Insight Drug profile 800009995], conducted in healthy volunteers [57] . Based on promising new results obtained from NIH sponsored independent laboratory research on human and related coronaviruses, Hemispherx will stockpile injectable and/or oral formats of Alferon® N and Ampligen® [58] .

In December 2003, Hemispherx initiated a strategic programme with Aplicare to package more than 100 000 sachets of Alferon LDO® (Low Dose Oral Interferon), as a topically applied experimental broad-spectrum immunotherapeutic/antiviral for SARS. This is designed to prevent the spread of SARS once the first cases are identified [59] [60] .

Hemispherx announced the initiation of a new joint multi-part clinical programme for the treatment of SARS in collaboration with Vanderbilt University in January 2004. As part of the programme, Alferon N Injection® will be used in a placebo-controlled, double-blind clinical trial to evaluate its efficacy in the treatment of SARS. In a parallel second trial Alfredo LDO® will be evaluated versus placebo for efficacy in prophylaxis of infection by SARS [61] . A further collaboration with the Princess Margaret Hospital in Hong Kong, announced in November 2004, involves a randomised dose-ranging study of Alferon® LDO in normal volunteers and or asymptomatic subjects with exposure to a person known to have SARS or possible SARS [62] .

Small cell lung cancer

Phase II development of interferon-α-n3 injection was underway in patients with small cell lung cancer in the US. However, no development was reported and development in this indication is presumed discontinued.

West Nile Virus programme

Clinical development of Alferon N Injection® was continuing for the treatment of West Nile virus infection. However, the company stated that its ability to continue the study was hampered by a significant reduction in the number of confirmed cases of the disease. An investigator sponsored US-based phase II/III trial is also being planned (Hemispherx Biopharma Form 10-K, March 2010).

Hemispherx has initiated a joint clinical programme with New York Hospital for the treatment of West Nile Virus (WNV) infection with Alferon N Injection®. The phase IIb placebo-controlled, double-blinded study is designed to evaluate the efficacy of Alferon® N when administered to patients with, or at high risk of, acute meningoencephalitis caused by WNV infection. In view of the spread of WNV infections into twelve states in the US, Hemispherx announced in July 2004 that it would be accelerating the clinical activities for Alferon®N. As of August 2007, enrolment in the phase IIb trial had reached approximately the 50% mark [63] [64] [65] [66] .

Zika virus infection

In February 2016, Hemispherx announced its intention to explore the oral use of Alferon® LDO in non-pregnant patients with Zika virus infection. The study aims to establish whether or not Alferon® 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 [67] .

Kaposi's sarcoma (AIDS-related)

Phase II trials were underway in Mexico in patients with AIDS-related Kaposi's sarcoma. However, development appears to have been discontinued.

Financing information

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 interferon-α-n3 as a preventative for seasonal and pandemic influenza [68] .

Patent Information

In January 2013, the US Patent Office granted Hemispherx three new patents in Australia, New Zealand and Singapore for the use of Alferon LDO® to treat bacterial or protozoan infections.

In January 2012, the US Patent Office granted Hemispherx Biopharma two patents for low-dose oral interferon alfa-n3 [45] .

Hemispherx Biopharma's US patent portfolio relating to the Alferon® products included US patent no.s 5 503 828 and 5 676 942 which expired in April 2013 and October 2014, respectively, and US patent no. 5 989 441, which was expected to expire in December 2017; however, the patent expired beforehand because a manufacturing methodology was no longer in use [69] .

In May 2004 Hemispherx announced that it had filed an expanded US patent application covering the use of Alferon N Injection®, and Alferon LDO® for the potential treatment and prevention of severe acute respiratory syndrome (SARS) and other emerging viruses.

Drug Properties & Chemical Synopsis

  • Route of administration Intralesional, PO, SC
  • Formulation Injection, unspecified
  • Class Anti-inflammatories, Antivirals, Interferons
  • Mechanism of Action Immunostimulants
  • WHO ATC code

    J05 (Antivirals for Systemic Use)

    J05A (Direct acting antivirals)

    J05A-X (Other antivirals)

    L03A-B01 (Interferon alfa natural)

    N07X (Other Nervous System Drugs)

  • EPhMRA code

    J5 (Antivirals for Systemic Use)

    J5B (Antivirals, excluding anti-HIV products)

    J5B4 (Influenza antivirals)

    J5C (HIV antivirals)

    L3B1 (Interferons, alpha)

    N7X (All other CNS drugs)

  • CAS Registry Number 99210-65-8

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

HIV-1 infections

Exclusion

CD4

1

HIV-1 infections

Inclusion

CD4

1

Biomarker

Drug Name Biomarker Name Biomarker Function
Interferon alpha n3 - AIM ImmunoTech CD4 Exclusion, Inclusion
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
Ebola virus infections - - No development reported (Research) USA PO / unspecified AIM ImmunoTech, United States Army Medical Research Institute of Infectious Diseases, Swiss Department of Defence, Civil Protection and Sport, National Institute of Allergy and Infectious Diseases, Howard University 28 Oct 2018
HIV infections - - No development reported (II) USA PO / unspecified AIM ImmunoTech 31 Dec 2007
Hepatitis C Patients that have failed or become intolerant to recombinant interferon treatment Treatment-experienced Registered Argentina SC / Injection AIM ImmunoTech 04 Mar 2013
Hepatitis C - - No development reported (III) Mexico SC / Injection AIM ImmunoTech 17 Sep 2003
Hepatitis C - - No development reported (II/III) USA SC / Injection AIM ImmunoTech 21 Oct 2009
Hepatitis C - - No development reported (II) Japan SC / Injection Fujimoto Pharmaceutical 17 Sep 2003
Human papillomavirus infections - - Marketed USA Intralesional / Injection AIM ImmunoTech 17 Nov 1995
Human papillomavirus infections Refractory or recurring disease Recurrent, Treatment-experienced Registered Argentina SC / Injection AIM ImmunoTech 26 Jan 2012
Human papillomavirus infections - - No development reported (I/II) Hong Kong, USA PO / unspecified AIM ImmunoTech 25 Mar 2015
Human papillomavirus infections - - Market Withdrawal Mexico SC / Injection AIM ImmunoTech 18 Jun 1996
Inflammation Patients that have failed or become intolerant to recombinant interferon treatment Treatment-experienced Registered Argentina SC / Injection AIM ImmunoTech 04 Mar 2013
Influenza A virus H7N9 subtype Prevention or treatment - No development reported (Preclinical) Switzerland, USA SC / unspecified AIM ImmunoTech 28 Jun 2018
Influenza A virus infections For avian influenza Prevention No development reported (Preclinical) Canada, USA PO / unspecified AIM ImmunoTech 04 Nov 2017
Influenza A virus infections For avian influenza Prevention No development reported (Preclinical) Canada, USA SC / Injection AIM ImmunoTech 04 Nov 2017
Influenza virus infections In hospitalised patients - No development reported (II) India PO / unspecified AIM ImmunoTech 25 Mar 2015
Influenza virus infections - - No development reported (I) USA PO / unspecified AIM ImmunoTech 04 Nov 2017
Kaposi's sarcoma - - Discontinued (II) Mexico SC / Injection AIM ImmunoTech 31 Dec 2004
Middle East respiratory syndrome coronavirus Biodefence purposes - No development reported (Research) USA SC / unspecified AIM ImmunoTech 04 Nov 2017
Multiple sclerosis Patients that have failed or become intolerant to recombinant interferon treatment Treatment-experienced Registered Argentina SC / Injection AIM ImmunoTech 04 Mar 2013
Small cell lung cancer - - Discontinued (II) USA SC / Injection AIM ImmunoTech 31 Dec 2004
Venezuelan equine encephalomyelitis Biodefence purposes - No development reported (Research) USA SC / unspecified AIM ImmunoTech 04 Nov 2017
Viral infections Patients that have failed or become intolerant to recombinant interferon treatment Treatment-experienced Registered Argentina SC / Injection AIM ImmunoTech 04 Mar 2013
West Nile virus infections - Prevention No development reported (II) USA SC / Injection AIM ImmunoTech 25 Mar 2015
Zika virus infection - - No development reported (Preclinical) USA PO / unspecified AIM ImmunoTech 28 Feb 2021

Orphan Status

Indication Patient Segment Country Organisation Event Date
Middle East respiratory syndrome coronavirus - European Union AIM ImmunoTech 20 Jan 2016

Commercial Information

Involved Organisations

Organisation Involvement Countries
Stem Cell Innovations Originator USA
AIM ImmunoTech Owner World
Andromaco Market Licensee Mexico
GP Pharm Market Licensee Argentina
Emerge Health Market Licensee Australia, New Zealand
Scientific Products Pharmaceutical Market Licensee Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates
Howard University Collaborator USA
National Institute of Allergy and Infectious Diseases Collaborator USA
Max Neeman International Collaborator India
Swiss Department of Defence, Civil Protection and Sport Collaborator Switzerland
United States Army Medical Research Institute of Infectious Diseases Collaborator USA
Bioclones Collaborator South-Africa

Brand Names

Brand Name Organisations Indications Countries
Alferon LDO AIM ImmunoTech Influenza A virus infections USA
Alferon N AIM ImmunoTech Human papillomavirus infections USA
Alferon N Gel AIM ImmunoTech Human papillomavirus infections Unknown
Alferon N Injection AIM ImmunoTech Human papillomavirus infections USA
Alferon N LDO AIM ImmunoTech HIV infections, Human papillomavirus infections USA
Altemol Andromaco Human papillomavirus infections Mexico
Naturaferon GP Pharm Human papillomavirus infections Argentina

Scientific Summary

  • Adverse Events Frequent: Hypertriglyceridaemia
    Occasional: Asthenia; Chills; Fever; Headache; Leucopenia; Muscle pain; Thrombocytopenia

Adverse Events

Typical adverse events associated with interferon-α-n3 therapy were seen in a phase II study of SC interferon-α-n3 (1.0-10.0MU) in 77 patients. These included: asthenia (n = 25), headache (20), leucopenia (18), fever (12), chills (10), myalgia (10), and thrombocytopenia (7) [77] .

The findings of a review by US-based researchers indicate that treatment with various forms of interferon-α (IFN-α) is associated with increased serum triglyceride levels. A review of 5 clinical trials identified 152 patients (mean age = 44.5 years) with chronic hepatitis C infection. The patients had been treated with various forms of IFN-α, including IFN-α-n3, with or without ribavirin. 24 weeks after stopping treatment, mean triglyceride levels had returned to baseline levels. The review found that the hypertriglyceridaemia is sometimes severe, but rarely associated with significant clinical consequences [72] .

Drug induced morbidity was significantly less in volunteers treated with interferon-α-n3 compared with those treated with the recombinant, bacteria derived interferon, Intron® A. In this double blinded study, 29 healthy volunteers (ages 18-50) were randomised to receive interferon-α-n3 (n=14) or Intron® A (15). The treatment consisted of 5 million units of interferon-α-n3 injection or Intron® A injection, five times per week for two weeks. One volunteer treated with interferon-α-n3 experienced chills compared with 11 volunteers treated with Intron® A (p<0.001). The number of volunteers who experienced fever was also lower (2 vs 9) in the interferon-α-n3 group compared with the Intron® A group (p<0.007) [57] .

Pharmacodynamics

Summary

Alferon® LDO demonstrated a dose-dependent, prevention of pulmonary damage, a characteristic of human fatal case arising due to primary influenza virus (H5N1) pneumonia, in non-human primate model. Alferon® LDO at highest dose of 62.5 IU/Kg showed marked reduction in alveolar inflammatory response in contrast to the haemorrhage and inflammatory response in treated animals compared with untreated animals. There were no reports of prevention of severe damage in the lower pulmonary airway to be associated with a parallel reduction in viral titers [39] .

Newborn piglets, treated with Alferon® N had significantly greater survival rates than placebo-treated piglets during an outbreak of porcine coronavirus infections. This study was conducted in a piglet population of 1740 animals, in Texas USA, living under typical field/farm conditions. During a natural outbreak of porcine coronavirus infections, groups of piglets were treated for four consecutive days with placebo or 1.0, 10.0 or 20.0 international units of Alferon® N. All dosages of Alferon N improved survival rates (p <0.01). A survival rate of 94.6% was seen in piglets that received the higher dosages (p<0.001) Alferon® N [71] .

Antimicrobial Activity

Summary

Interferon-α-n3 dose-dependently inhibited replication of Middle East Respiratory Syndrome (MERS) coronavirus in monkey kidney cells. In these in vitro studies, monkey kidney cells were treated with interferon-α-n3 either 18h prior or 1h after exposure of the cells to the coronavirus. Coronavirus titres were assessed on days 1 and 3 after infection [12] .

Additional in vitro studies confirmed the inhibitory effect of interferon-α-n3 on MERS coronavirus infections. In these studies, treatment with interferon-α-n3 24 hours prior to infection significantly and dose-dependently reduced virus titres in supernatants that were collected from cells at 36 hours after infection [21] .

In vitro

data demonstrated that interferon-α-n3 inhibited neuraminidase inhibitor resistant Shanghai/1/H7N9 virus, and inhibited replication of wild type and 292K H7N9 viruses. Both oseltamivir and Interferon-α-n3 showed significant inhibition of neuraminidase inhibitor sensitive H7N9 influenza virus [22] .

In vitro

studies in A549 cells demonstrated that interferon-α-n3 was active against an oseltamivir-sensitive wild-type human A(H7N9) influenza isolate A/Anhui/1/2013, and an oseltamivir-resistant patient influenza isolate (A/Shanghai/1/2013 (NA-292K; Shanghai 1-NA292K) [23] [78] .

Interferon-α-n3 [Alferon N®] was 10- to 100-fold more effective than equal concentrations of recombinant interferon-α-2b or recombinant interferon-α-2a, respectively, for inhibition of HIV in infected monocytes. It also had a higher maximal inhibition of HIV reverse transcriptase activity with an ID50 value of 1.2 IU/ml compared with values of 13.7 and 95 IU/ml for recombinant interferon-α-2b and recombinant interferon-α-2a, respectively [82] .

Interferon-α-n3 inhibits SARS-coronavirus (SARS-CoV) at a high specific activity in Vero 76 cells. Vero cells infected with coronavirus at a MOI of 0.001 visually exhibited 100% cytopathic effect over a 3-5 day incubation period without treatment. Interferon-α-n3 inhibited SARS-CoV at EC50 values of 5 696 ±1 703 IU/ml (visual) and 10 740 ±5 161 IU/ml (neutral red). Viral load reduction by one log10 was 78 000 ±22 000 IU/ml [70] .

Nineteen antiviral drugs approved for clinical use (for viral infections other than SARS), were tested in an in vitro model of SARS-CoV infection. High titres of SARS-CoV, originally isolated from a respiratory sample of a SARS patient and propagated in Vero E6 cells were completely inhibited by Alferon® N at 5000 IU/mL. Complete inhibition of cytopathic effects was only observed in 4/19 compounds and Alferon® N inhibited SARS-CoV at the lowest level (5000 IU/mL) of all tested compounds [56] .

Therapeutic Trials

In a retrospective analysis, brain magnetic resonance imaging was performed in 69 patients with multiple sclerosis who were either treated with interferon-α-n3 or untreated. The majority of patients in the interferon-α-n3 treatment group had received interferon-α-n3 after adverse reactions were experienced with other agents, such as interferon-β-1a. Interferon-α-n3 was also used in patients with very active multiple sclerosis, rapidly progressive disease or those with advanced disability who were judged unlikely to benefit from or tolerate interferon-β-1a. Gadolinium-enhanced lesions were observed in 6% of patients treated with interferon-α-n3 for 3-6 months, compared with 37% of patients in the untreated control group. Expanded disability status scale (EDSS) scores were recorded over a mean 11 months of follow-up - decreasing from 4.8 to 3.4 in patients treated with interferon and increasing from 3.8 to 4.5 in untreated patients [73] .

A retrospective review compared MRI scans from 40 patients with multiple sclerosis treated with interferon-α-n3 to scans from 40 patients treated with interferon-β-1b (Betaseron®). There was a reduction in the volume of T2-weighted brain lesions in both treatment groups (−10% for interferon-α-n3 and −7% for interferon-β-1b) relative to an untreated control group (+12%). EDSS scores were evaluated at baseline and at 12 months in 38 interferon-α-n3 recipients and 31 interferon-β-1b recipients. EDSS was reduced by 1.07 points with interferon-α-n3 and by 0.16 points with interferon-β-1b, compared with an increase of 0.8 points in untreated control patients [73] .

H

IV-1 infection: In a phase I multicentre trial, interferon-α-n3 was administered SC to 20 early stage HIV-1-infected patients (CD4 counts > 400 cells/mm3) three times weekly for 12 weeks. 15 patients continued treatment for another 12 weeks. Doses of interferon-α-n3 ranged from 1 MU/dose to the maximum tolerated dose (average 44 MU/week). A reduction in serum HIV-1 RNA levels was observed soon after induction of treatment and was correlated with dose given. Long term follow-up showed a significant delay in CD4 count reduction. The average CD4 count 21 months after initiation of therapy was 538 cells/mm3 compared with an expected count of 381 cells/mm3 (p < 0.002) [79] .

In a double-blind study, 41 ARC patients (CD4 counts 100-350 cells/mm3) received low dose oral interferon-α-n3 150 IU/day or placebo, for 6 weeks. 36 patient then continued in an open study of interferon-α-n3 150 IU/day for a further 48 weeks. The reduction in CD4 counts were similar in both groups. Weight change, incidence of fever and prevalence of thrush were also similar. However, prevalence and severity of common symptoms such as anorexia and fatigue showed significant improvement in the interferon-α-n3 recipients compared with the placebo recipients (11.8% vs 5.6% decrease, respectively). During the open phase of the study, symptomatic improvement was maintained in the primary interferon-α-n3 recipients and achieved in those who initially received placebo. Treatment did not appear to affect CD4 counts although only 1 patient progressed to AIDS during the 23.3 patient-years of interferon-α-n3 treatment [80] .

Results from a pilot dose-ranging study suggested that interferon-α-n3 administered 3 times weekly at ≥ 10MU reduced viraemia compared with placebo over 24 weeks of therapy in asymptomatic patients with baseline CD4 levels ≥ 400 cells/µl [74] .

Papillomavirus infection

The efficacy of interferon-α-n3 [Alferon N®] for the treatment of condylomata acuminata was tested in a double-blind, randomised, placebo-controlled trial involving 156 evaluable patients. Interferon-α-n3 (mean dose of 225 000 IU/wart and 920 000 IU/patient/treatment session) was injected into lesions twice weekly for 8 weeks or until all treated warts resolved. Interferon-α-n3 was shown to be significantly more effective than placebo in reducing the size and number of warts/patient and causing the complete disappearance of all warts. 80% of interferon-α-n3 recipients had complete or partial responses compared with 44% of patients receiving placebo (p < 0.001). Of these patients, 54% of interferon-α-n3 recipients and 20% of patients receiving placebo had complete resolution [81] .

Chronic hepatitis C infection

In a phase II study, 77 previously untreated patients with chronic hepatitis C were randomised to receive interferon- α -n3 1.0, 2.5, 5.0 or 10.0 MU SC three times a week for 24 weeks and then followed for an additional 24 weeks. At the end of the treatment 67% of patients in the 10MU group had a normal ALT level and 59% had undetectable hepatitis C virus RNA. After 24 weeks of follow-up, normal ALT and undetectable hepatitis C virus RNA occurred in 44% and 24% of patients, respectively. Lower doses were much less effective. As interferon-α-n3 is a natural product, it did not induce neutralising anti-interferon antibodies during or after the treatment period [77] .

Patients with chronic hepatitis C who had not responded to prior interferon therapy were included in a study of concomitant therapy with interferon-α-n3 and ribavirin. They were randomised to receive oral ribavirin 1 g/day for 6 months followed by IFN-α-n3 3MU 3 times weekly for a further 6 months (group 1; n=33), oral ribavirin 1 g/day plus IFN-α-n3 3MU 3 times weekly for 6 months (group 2; 33) or IFN-α-n3 3MU 3 times weekly for 6 months (group 3; 30). At the end of treatment, 10, 41 and 17% of patients from groups 1, 2 and 3, respectively, had normal ALT levels. However, 6 months after completing therapy, only 12.5% of patients in group 2 had normal ALT levels. Nonsignificant reductions in HCV RNA levels were observed in all 3 treatment groups at the end of therapy, however, mean HCV RNA levels had returned to baseline by the end of follow-up [76] .

There was no significant difference between the efficacy and tolerability of recombinant interferon-α-2b compared with interferon-α-n3 for treating patients with chronic liver disease induced by hepatitis C virus. Patients in the study had mild chronic hepatitis (n = 34), moderate-severe chronic hepatitis (81) or active cirrhosis (53). Baseline hepatitis C virus RNA level was 5.3 × 106 Eq/ml for patients receiving interferon-α-2b and 6.3 × 106 Eq/ml for patients receiving interferon-α-n3; 83 and 80% of patients, respectively, were anti-hepatitis C virus immunoglobulin M seropositive [75] .

Development History

Event Date Update Type Comment
28 Feb 2021 Phase Change - No development reported No recent reports of development identified for preclinical development in Zika-virus-infection in USA (PO) Updated 28 Feb 2021
23 Aug 2019 Company Involvement Hemispherx Biopharma is now called AIM ImmunoTech Updated 05 Sep 2019
08 Feb 2019 Active Status Review 9259972: No updates Updated 08 Feb 2019
28 Oct 2018 Phase Change - No development reported No recent reports of development identified for research development in Ebola-virus-infections in USA (PO) Updated 28 Oct 2018
28 Jun 2018 Phase Change - No development reported No recent reports of development identified for preclinical development in Influenza-A virus H7N9 subtype in Switzerland (SC) Updated 28 Jun 2018
24 Jun 2018 Biomarker Update Biomarkers information updated Updated 31 Aug 2018
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for phase-I development in Influenza-virus-infections in USA (PO) Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for preclinical development in Influenza-A virus H7N9 subtype in USA (SC) Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for preclinical development in Influenza-A-virus-infections(Prevention) in Canada (PO) Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for preclinical development in Influenza-A-virus-infections(Prevention) in Canada (SC, Injection) Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for preclinical development in Influenza-A-virus-infections(Prevention) in USA (PO) Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for preclinical development in Influenza-A-virus-infections(Prevention) in USA (SC, Injection) Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for research development in Middle-East-respiratory-syndrome-coronavirus in USA (SC) Updated 04 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for research development in Venezuelan equine encephalomyelitis in USA (SC) Updated 04 Nov 2017
06 Jun 2016 Licensing Status Hemispherx irrevocabaly obtains all intellectual property related to Alferon® under a comprehensive omnibus assignment [3] Updated 09 Jun 2016
31 May 2016 Licensing Status Hemispherx renews the sales, marketing, distribution and supply agreement with GP Pharm for interferon alpha n3 in Latin America [10] Updated 06 Jun 2016
04 Apr 2016 Licensing Status Hemispherx Biopharma and Scientific Products Pharmaceutical agree to co-promote Interferon-alpha-n3 in Saudi Arabia, United Arab Emirates, Kuwait, Oman, Qatar, and Bahrain, for Middle East respiratory syndrome [4] Updated 07 Apr 2016
09 Feb 2016 Trial Update Hemispherx plans a clinical trial for Zika virus infections [67] Updated 11 Feb 2016
03 Feb 2016 Phase Change - Preclinical Preclinical trials in Zika virus infection in USA (PO) Updated 11 Feb 2016
20 Jan 2016 Regulatory Status Interferon-alpha-n3 (Alferon N Injection®) receives Orphan Drug status for Middle East Respiratory Syndrome in European Union [50] Updated 21 Jan 2016
19 Oct 2015 Regulatory Status Committee for Orphan Medicinal Products recommends orphan drug designation for Interferon-alpha-n3 in European Union for Middle East respiratory syndrome [51] Updated 22 Oct 2015
11 Aug 2015 Licensing Status Hemispherx and Emerge Health agree to co-promote interferon-alpha-n3 under a named patient programme and to seek regulatory approval in Australia and New Zealand for Human papillomavirus infections (Intralesional) [5] Updated 17 Aug 2015
15 Jul 2015 Regulatory Status Hemispherx Biopharma applies for Orphan Drug status in Middle East respiratory syndrome in Europe [52] Updated 21 Jul 2015
25 Mar 2015 Active Status Review The product is approved for Human papillomavirus infections in Argentina Updated 24 Sep 2015
25 Mar 2015 Phase Change - No development reported(I/II) No development reported - Phase-I/II for Human papillomavirus infections in Hong Kong (PO) Updated 25 Mar 2015
25 Mar 2015 Phase Change - No development reported(I/II) No development reported - Phase-I/II for Human papillomavirus infections in USA (PO) Updated 25 Mar 2015
25 Mar 2015 Phase Change - No development reported(II) No development reported - Phase-II for Influenza virus infections in India (PO) Updated 25 Mar 2015
25 Mar 2015 Phase Change - No development reported(II) No development reported - Phase-II for West Nile virus infections (Prevention) in USA (SC) Updated 25 Mar 2015
02 Mar 2015 Regulatory Status US FDA accepts amended BLA for Interferon-alpha-n3 for Human papillomavirus infections for review before March 2015 [31] Updated 09 Sep 2015
29 Sep 2014 Company Involvement Hemispherx enters into five research collaborations to develop therapeutic cocktails against Ebola virus infections [15] Updated 02 Oct 2014
22 Sep 2014 Scientific Update Pharmacodynamics data from preclinical trial in Influenza virus infections (H5N1) released by Hemispherx Biopharma [38] Updated 26 Sep 2014
10 Sep 2014 Company Involvement Hemispherx establishes a research agreement with Swiss Department of Defense, Civil Protection and Sports for the development of Interferon-α-n3 in Ebola virus infections [14] Updated 15 Sep 2014
08 Sep 2014 Phase Change Early research in Ebola virus infections in USA (PO) [20] Updated 06 Nov 2014
08 Jul 2014 Licensing Status Hemispherx and Bioclones enter into an agreement for clinical trials of interferon-alpha-n3 in South Africa [11] Updated 15 Jul 2014
03 Jun 2014 Scientific Update Antimicrobial data from an in vitro study in Middle East Respiratory Syndrome coronavirus released by Hemispherx [21] Updated 13 Jun 2014
21 May 2014 Company Involvement Hemispherx establishes a research agreement with Swiss Department of Defense, Civil Protection and Sports for the development of Interferon-α-n3 in Influenza-A virus H7N9 [13] Updated 21 May 2014
14 May 2014 Phase Change - Preclinical Preclinical trials in Influenza-A virus H7N9 subtype in Switzerland (SC) Updated 21 May 2014
06 May 2014 Scientific Update Antimicrobial data from an in vitro study in Middle East Respiratory Syndrome coronavirus released by Hemispherx [12] Updated 14 May 2014
07 Jan 2014 Scientific Update Antimicrobial data from an in vitro study in Influenza virus infections released by Hemispherx Biopharma [22] Updated 17 Jan 2014
01 Dec 2013 Trial Update Hemispherx Biopharma discontinues phase II trial in Influenza A virus infection in India (CTRI/2010/091/001115) Updated 09 Jul 2014
18 Sep 2013 Scientific Update Antimicrobial data from an in vitro study in Influenza virus infections released by Hemispherx Biopharma [23] Updated 18 Sep 2013
12 Sep 2013 Phase Change Early research in Middle-East respiratory syndrome coronavirus in USA (SC) Updated 18 Sep 2013
12 Sep 2013 Phase Change Early research in Venezuelan equine encephalomyelitis in USA (SC) Updated 18 Sep 2013
26 Aug 2013 Phase Change - Preclinical Preclinical trials in Influenza-A virus H7N9 subtype (prevention and treatment) in USA (SC) Updated 18 Sep 2013
26 Aug 2013 Phase Change - Preclinical Preclinical trials in Influenza A virus infections (prevention) in USA (PO) Updated 29 Aug 2013
26 Aug 2013 Phase Change - Preclinical Preclinical trials in Influenza A virus infections (prevention) in Canada (PO) Updated 29 Aug 2013
26 Aug 2013 Phase Change - Preclinical Preclinical trials in Influenza A virus infections (prevention) in Canada (SC) Updated 29 Aug 2013
26 Aug 2013 Phase Change - Preclinical Preclinical trials in Influenza A virus infections (prevention) in USA (SC) Updated 29 Aug 2013
04 Mar 2013 Phase Change - Registered Registered for Hepatitis C (patients that have failed or become intolerant to recombinant interferon treatment) in Argentina (SC) Updated 06 Mar 2013
04 Mar 2013 Phase Change - Registered Registered for Inflammation (patients that have failed or become intolerant to recombinant interferon treatment) in Argentina (SC) Updated 06 Mar 2013
04 Mar 2013 Phase Change - Registered Registered for Multiple sclerosis (patients that have failed or become intolerant to recombinant interferon treatment)in Argentina (SC) Updated 06 Mar 2013
04 Mar 2013 Phase Change - Registered Registered for Viral infections (patients that have failed or become intolerant to recombinant interferon treatment) in Argentina (SC) Updated 06 Mar 2013
08 Oct 2012 Licensing Status The licensing agreements with Engitech in the US, Cell Pharm in Germany, Edward Keller Ltd. in Hong Kong and Guangdong Medicine Group in China for interferon-α-N3 appear to have been discontinued (http://www.hemispherx.net) Updated 08 Oct 2012
01 Oct 2012 Phase Change - Preregistration Preregistration for Hepatitis C in Argentina (SC) Updated 05 Oct 2012
26 Jan 2012 Phase Change - Registered Registered for Human papillomavirus infections (refractory or reccuring disease) in Argentina (SC) Updated 27 Jan 2012
17 Aug 2011 Phase Change - Preregistration Preregistration for Human papillomavirus infections in Argentina (SC) Updated 19 Aug 2011
07 Jan 2011 Active Status Review Phase-I/II development of Alferon LDO® is ongoing in USA and Hong Kong Updated 07 Jan 2011
20 Dec 2010 Licensing Status Alferon N Injection® licensed to GP Pharm in Argentina, with an option for other Latin American countries [9] Updated 24 Dec 2010
10 Nov 2010 Company Involvement Hemispherx receives grant through the US Qualifying Therapeutic Discovery Project programme for interferon-alpha-n3 development in Influenza (prevention) [68] Updated 15 Nov 2010
19 Jul 2010 Phase Change - II Phase-II clinical trials in Influenza virus infections in India (PO) Updated 28 Jul 2010
13 Jul 2010 Regulatory Status Indian Drugs Controller General approves phase II trial application for Interferon-alpha-n3 in hospitalised patients with Influenza virus infections [42] Updated 28 Jul 2010
12 Mar 2010 Active Status Review Interferon-alpha-n3 (oral) is still in Phase-I trials for Influenza virus infections in USA Updated 08 Apr 2010
31 Oct 2009 Regulatory Status Hemispherx Biopharma submits protocol for Phase-II trial in Influenza virus infections to the US FDA Updated 09 Apr 2010
21 Oct 2009 Phase Change - No development reported(II/III) No development reported - Phase-II/III for Hepatitis C in USA (SC) Updated 21 Oct 2009
31 Dec 2007 Phase Change - No development reported(II) No development reported - Phase-II for HIV infections in USA (PO) Updated 07 Jan 2011
08 Aug 2006 Licensing Status Hemispherx has purchased the royalty interest on sales of interferon-α-n3 products from Stem Cell Innovations Updated 08 Aug 2006
20 Dec 2005 Phase Change - I/II Phase-I/II clinical trials in Human papillomavirus infections in Hong Kong (PO) Updated 28 Dec 2005
20 Dec 2005 Phase Change - I/II Phase-I/II clinical trials in Human papillomavirus infections in USA (PO) Updated 28 Dec 2005
19 May 2005 Phase Change - I Phase-I clinical trials in Coronavirus infections in USA (unspecified route) Updated 19 May 2005
16 May 2005 Phase Change - I Phase-I clinical trials in Influenza virus infections in USA (PO) Updated 05 Jun 2007
23 Mar 2005 Phase Change - Preclinical Preclinical trials in Influenza virus infections in USA (PO) Updated 05 Jun 2007
31 Dec 2004 Phase Change - Discontinued Development discontinued for Kaposi's sarcoma before 2004 Updated 07 Jan 2011
31 Dec 2004 Phase Change - Discontinued Development discontinued for Small cell lung cancer before 2004 Updated 07 Jan 2011
21 Jun 2004 Phase Change - II Phase-II clinical trials in Multiple sclerosis in USA (Injection) Updated 21 Jun 2004
22 Apr 2004 Scientific Update Preclinical data from a media release have been added to the Viral Infections antimicrobial activity section [56] Updated 22 Apr 2004
22 Mar 2004 Company Involvement Hemispherx has completed the acquisition of worldwide rights to Alferon N® Updated 22 Mar 2004
08 Mar 2004 Phase Change - II Phase-II clinical trials in HIV infections treatment in USA (PO) Updated 08 Mar 2004
28 Jan 2004 Phase Change - II Phase-II clinical trials in West Nile virus infections in USA (Injection) Updated 28 Jan 2004
13 Nov 2003 Phase Change - Preclinical Preclinical trials in Coronavirus infections in USA (unspecified route) Updated 13 Nov 2003
13 Nov 2003 Scientific Update Preclinical data from a media release have been added to the Viral Infections antimicrobial activity section [70] Updated 13 Nov 2003
17 Sep 2003 Phase Change - No development reported(Clinical) No development reported - Clinical-Phase-Unknown for Multiple sclerosis in USA (Injection) Updated 17 Sep 2003
17 Sep 2003 Phase Change - No development reported(II) No development reported - Phase-II for Hepatitis C in Japan (Injection) Updated 17 Sep 2003
17 Sep 2003 Phase Change - No development reported(II) No development reported - Phase-II for Kaposi's sarcoma in Mexico (unspecified route) Updated 17 Sep 2003
17 Sep 2003 Phase Change - No development reported(II) No development reported - Phase-II for Small cell lung cancer in USA (unspecified route) Updated 17 Sep 2003
17 Sep 2003 Phase Change - No development reported(III) No development reported - Phase-III for Hepatitis C in Mexico (Injection) Updated 17 Sep 2003
17 Sep 2003 Phase Change - II/III Phase-II/III clinical trials in Hepatitis C in USA (Injection) Updated 17 Sep 2003
17 Sep 2003 Phase Change - II/III Phase-II/III clinical trials in HIV infections treatment in USA (PO) Updated 17 Sep 2003
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 Alferon N in China for Hepatitis C Updated 08 Sep 2003
21 Aug 2003 Licensing Status Hemispherx has entered into a sales and marketing agreement with Engitech to promote Alferon N® in the US Updated 21 Aug 2003
05 Jun 2003 Scientific Update Data from a media release have been added to the adverse events section [57] Updated 05 Jun 2003
22 May 2003 Scientific Update Preclinical data from a media release have been added to the Viral Infections pharmacodynamics section [71] Updated 22 May 2003
17 Mar 2003 Company Involvement Hemispherx has acquired certain assests of Interferon Sciences, including the rights to interferon-α-n3 [6] Updated 17 Mar 2003
21 Dec 2001 Scientific Update Data from a review of clinical studies have been added to the adverse events section [72] Updated 21 Dec 2001
20 Nov 2001 Scientific Update Retrospective data have been added to the Neurological Disorders therapeutic trials section [73] Updated 20 Nov 2001
08 Aug 2001 Phase Change Investigation in Multiple sclerosis in USA (Injection) Updated 08 Aug 2001
26 Nov 1998 Scientific Update A dose-ranging study of HIV-infected patients has been added to the Viral infections therapeutic trials section [74] Updated 26 Nov 1998
13 Oct 1998 Scientific Update A study has been added to the Viral infections therapeutic trials section [75] Updated 13 Oct 1998
05 Oct 1998 Scientific Update A study has been added to the Viral infections therapeutic trials section [76] Updated 05 Oct 1998
15 Apr 1997 Scientific Update A study has been added to the Viral infections therapeutic trials and adverse events sections [77] Updated 15 Apr 1997
25 Oct 1996 Phase Change - III Phase-III clinical trials for HIV infections treatment in USA (PO) Updated 25 Oct 1996
13 Oct 1996 Phase Change - II Phase-II clinical trials for Small cell lung cancer in USA (Unknown route) Updated 13 Oct 1996
22 Jul 1996 Phase Change - III Phase-III clinical trials for Hepatitis C in Mexico (Injection) Updated 22 Jul 1996
19 Jul 1996 Phase Change - III Phase-III clinical trials for Hepatitis C in USA (Injection) Updated 19 Jul 1996
10 Jul 1996 Phase Change - III Phase-III clinical trials for HIV infections treatment in USA (Injection) Updated 10 Jul 1996
18 Jun 1996 Phase Change - Marketed Launched for Human papillomavirus infections in Mexico (Injection) Updated 18 Jun 1996
23 May 1996 Phase Change - II Phase-II clinical trials for Hepatitis C in USA (Injection) Updated 23 May 1996
12 Dec 1995 Phase Change - II Phase-II clinical trials for HIV-1 infections in USA (PO) Updated 12 Dec 1995
17 Nov 1995 Phase Change - Marketed Launched for Human papillomavirus infections in USA (Intralesional) Updated 17 Nov 1995
17 Nov 1995 Phase Change - II Phase-II clinical trials for Small cell lung cancer (Unknown route) Updated 17 Nov 1995
17 Nov 1995 Phase Change - III Phase-III clinical trials for HIV-1 infections (PO) Updated 17 Nov 1995
09 Nov 1995 Phase Change - II Phase-II clinical trials for Hepatitis C in Japan (Injection) Updated 09 Nov 1995
09 Nov 1995 Phase Change - II Phase-II clinical trials for Kaposi's sarcoma in Mexico (Unknown route) Updated 09 Nov 1995

References

  1. USAMRIID Reports Genetic Changes in Ebola Virus May Impede Potential Treatments.

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

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

    Media Release
  4. Hemispherx Biopharma Enters into Alfa-n3 Interferon Clinical Trial, Sales, Marketing, Distribution, and Supply Agreement with Saudi Arabias Premier Pharma Company in Fight Against the Deadly MERS Disease.

    Media Release
  5. Hemispherx Expands Its Collaboration With Emerge Health for the Commercialization of Alferon in Australia and New Zealand.

    Media Release
  6. Hemispherx Acquires Rights for Only FDA Approved Natural Alpha Interferon Drug Company.

    Media Release
  7. Hemispherx Biopharma Completes Acquisition for Worldwide Rights to Alferon N.

    Media Release
  8. Hemispherx Biopharma Announces Purchase of Royalty Interest from Stem Cell Innovations, Inc.; Only Natural Alpha Interferon Product on the U.S. Market.

    Media Release
  9. Hemispherx Biopharma Licenses Alferon N Injection(R) to GP Pharm in Latin America.

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

    Media Release
  11. Hemispherx Biopharma and Bioclones Join Forces in Effort to Eradicate HIV/AIDS Virus Based on Recent Clinical Insights of Wistar Institute, University of Pennsylvania.

    Media Release
  12. Alferon(R) N Effective Against MERS (Middle East Respiratory Syndrome) Virus In-Vitro.

    Media Release
  13. Hemispherx Biopharma Formally Collaborates With the Swiss Department of Defense, Civil Protection and Sports to Study Alferon(Rm) Against Tamiflu Resistant Influenza Virus Strains.

    Media Release
  14. 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
  15. Hemispherx Biopharma Expands Research on Potential Ebola Treatments to Five Independent Experts/Institutional Collaborators.

    Media Release
  16. Hemispherx Biopharma Enters Into Direct Supply Agreement With Gulf Coast Regional Blood Center to Supply Leukocytes to Manufacture Alferon N Injection(R).

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

    Media Release
  18. Hemispherx Biopharma Enters into Sales and Marketing Agreement with Engitech for Alferon N; Agreement Provides Nationwide Sales Team for Alferon N.

    Media Release
  19. 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
  20. 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
  21. Hemispherx Announces That the University of Texas Medical Branch Confirms Activity of Alferon(Rm) N Against MERS (Middle East Respiratory Syndrome) Virus.

    Media Release
  22. Hemispherx Biopharma Reports Evidence Based Clinical Potential of a Natural Interferon (IFN) -- Alpha for Infection Control and Treatment of Drug Resistant H7N9 Influenza Virus.

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

    Media Release
  24. Hemispherx Biopharma Board Appoints New President.

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

    Media Release
  26. Hemispherx Biopharma Director Dr. William Mitchell to Present Research on Treating Deadly Emerging Viruses During the 4th World Congress on Virology October 8.

    Media Release
  27. A study to assess the safety and biological effects of adding interferon-alpha-n3 to a strategic therapeutic intervention protocol in African patients with HIV

    ctiprofile
  28. A randomized, dose-ranging study of Alferon (R) LDO [low dose interferon alfa-n3 (human leukocyte derived)] in asymptomatic HIV+ subjects

    ctiprofile
  29. Hemispherx Biopharma Announces FDA Authorization for a Clinical Study with New Biological Alferon LDO for HIV; Company to Initiate Phase II Study in Early-Stage HIV Patients.

    Media Release
  30. Hemispherx Biopharma to Present at the 17th Annual Rodman & Renshaw Global Investment Conference in New York City September 8-10, 2015.

    Media Release
  31. Hemispherx Biopharma Announces the Completion of the Newly Upgraded Alferon(Rm) Facility: Commercial Production of Alferon(Rm) is in the Final Stage Integrating Continuous Flow Manufacturing Technology.

    Media Release
  32. Photo Release -- Hemispherx Biopharma Fully Aligns Executive Bonus Programs to Accelerate Product Revenue Opportunities and Market Entry.

    Media Release
  33. Hemispherx Biopharma Gains Broad Treatment Expansion for Alferon N Injection in Argentina.

    Media Release
  34. Hemispherx Biopharma Files for Treatment Expansion in Argentina for Alferon N Injection(R) for Hepatitis C.

    Media Release
  35. Hemispherx Biopharma Gains Regulatory Approval in Latin America.

    Media Release
  36. Hemispherx Biopharma Submits for Regulatory Approval of Alferon(R) in Argentina.

    Media Release
  37. Hemispherx to Present at the 4th Annual Biodefense Research Meeting Sponsored by the American Society of Microbiology; Ampligen(R) and Alferon(R) in Global Clinical / Animal Trials Against Avian Influenza.

    Media Release
  38. Hemispherx Presents New Data on Protection From Pulmonary Damage Associated With Infection by Highly Pathogenic Influenza Virus.

    Media Release
  39. Hemispherx Announces Primate Research Showing Alferon(Rm) LDO Protection From Pulmonary Damage Associated With Infection by Highly Pathogenic Influenza Virus.

    Media Release
  40. Director of the U.S. Department of Homeland Security Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD), Professor J. Richt, DVM, Ph.D., to Present Programs to Potentially Reduce Pandemic Influenza Spread.

    Media Release
  41. Hemispherx Announces Biosecurity Program to Potentially Reduce Pandemic Influenza Threat.

    Media Release
  42. The Indian Drugs Controller General Approves Start of Clinical Study of Hemispherx Biopharma's Natural Interferon Product, Alferon N Injection(R), in Hospitalized Flu Patients.

    Media Release
  43. Hemispherx Biopharma and Max Neeman International Team Initiate Influenza Research Programs.

    Media Release
  44. A Double Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Interferon Alfa-N3 Therapy in Addition to Standard of Care in Adults Hospitalized Due to Acute Severe Influenza.

    ctiprofile
  45. Hemispherx Biopharma Receives U.S. Patent Office Notification of Two New Patents Granted for Alferon(R) LDO.

    Media Release
  46. Phase II trial investigating the efficacy and tolerability of low-dose oral interferon alpha-n3 (Alferon LDO) for the prevention and treatment of influenza in a family setting.

    ctiprofile
  47. Hemispherx Biopharma Enters Research Agreement with Defence R&D Canada.

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

    Media Release
  49. Hemispherx Presents Potential Avian Influenza Treatment Breakthrough at Paris Conference.

    Media Release
  50. Hemispherx Biopharma Europe N.V./S.A. : Orphan Medicine Designation and European Medicines Agency Public Opinion Summary Published by EMA Regarding Alferon N Injection(R) as a Treatment of Middle East Respiratory Syndrome (MERS).

    Media Release
  51. Hemispherx Biopharma Europe N.V./S.A. Receives Positive Opinion on Application for Orphan Designation by the European Medicines Agency for Alferon N Injection to Treat Patients With Middle East Respiratory Syndrome (MERS).

    Media Release
  52. Hemispherx Biopharma Europe N.V./S.A. Submits Application for Orphan Medicine Designation to the EMA for Alferon N Injection(R) for Treatment of Middle East Respiratory Syndrome (MERS).

    Media Release
  53. Hemispherx Biopharma Receives FDA Authorization for Clinical Trial in Multiple Sclerosis; Trial Approved for Patients in Resistant / Intolerant MS Group.

    Media Release
  54. Hemispherx Biopharma Launches Multiple Sclerosis Salvage Program with Natural Interferons.

    Media Release
  55. Hemispherx Initiates Collaboration on SARS with Genome Institute of Singapore.

    Media Release
  56. Hemispherx Biopharma Reports Publication Showing Superior Activity of Alferon Against SARS; Alferon Highest Activity Against SARS Among 19 Clinically Approved Compounds.

    Media Release
  57. Hemispherx Reports Data on Alferon at SARS Conference.

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

    Media Release
  59. Hemispherx Biopharma Expands Applications for Alferon Through New Manufacturing Agreement.

    Media Release
  60. Hemispherx Biopharma Accelerates New Oral SARS Prevention Program; Company's Oral Interferon Could Potentially Stem Next Outbreak of Disease.

    Media Release
  61. Hemispherx Biopharma Announces Joint SARS Clinical Program with Vanderbilt University.

    Media Release
  62. Hemispherx Biopharma Initiates Alferon LDO Clinical Program in Collaboration with Princess Margaret Hospital in Hong Kong.

    Media Release
  63. Double Blinded, Placebo Controlled Trial of Alpha Interferon Therapy for West Nile Meningoencephalitis

    ctiprofile
  64. Hemispherx Biopharma Accelerates Enrollment in West Nile Virus Controlled Trial of Alferon N as Cases Increase Nationwide.

    Media Release
  65. Hemispherx Biopharma Provides Update On West Nile Virus Program; Alferon-N Well-Controlled Clinical Trial Accelerates as New Human Cases of WNV Reported in Twelve States.

    Media Release
  66. Hemispherx Biopharma Announces Joint West Nile Virus Clinical Program with New York Hospital.

    Media Release
  67. 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
  68. Hemispherx Biopharma Receives Therapeutic Discovery Project Grant From U.S. Department of Treasury.

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

    Available from: URL: https://www.sec.gov/Archives/edgar/data/946644/000149315217003242/form10-k.htm
  70. Hemispherx Biopharma Reports New SARS Data on Alferon at the 14th International Antiviral Symposium.

    Media Release
  71. Hemispherx Reports Positive Independent Study Results of Alferon N in the Treatment of Pig Coronavirus -Animal Model of SARS-.

    Media Release
  72. Naeem M, Bacon BR, Mistry B, Britton RS, Di Bisceglie AM. Changes in serum lipoprotein profile during interferon therapy in chronic hepatitis C. Am-J-Gastroenterol 2001;962468-2472.

    PubMed | CrossRef Fulltext
  73. Data on the use of interferon alfa-n3 in the treatment of multiple sclerosis presented at the XVII World Congress of Neurology Meeting.

  74. Brand D, Beal J, Plasse T, Alferon HIV Study Group, et al. Natural interferon alpha treatment of HIV patients: a randomized, placebo-controlled, double-blind study. 38th-ICAAC 1998;393.

  75. Ascione A, De Luca M, Guardascione MA, Canestrini C, Galeota Lanza A, et al. Recombinant vs leucocytic interferon in the treatment of HCV chronic liver disease: final report of a randomized controlled trial. J-Hepatol 1998;28 (Suppl. 1)191.

  76. Sostegni R, Ghissetti V, Pittaluga F, Marchiaro G, Rocca G, et al. Sequential versus concomitant administration of ribavirin and interferon alfa-n3 in patients with chronic hepatitis C not responding to interferon alone: results of a randomized, controlled trial. Hepatology 1998;28341-346.

    PubMed | CrossRef Fulltext
  77. Simon DM, Gordon SC, Kaplan MM, Koff RS, Regenstein F, et al. Treatment of chronic hepatitis C with interferon alfa-n3: a multicenter, randomized, open-label trial. Hepatology 1997;25445-448.

    PubMed | CrossRef Fulltext
  78. Natural Human Interferon (Alpha-n3) is Active Against Both Wild-Type and Oseltamivir Resistant Avian-Origin Influenza A (H7N9) Virus.

    Media Release
  79. Meltzer MS, Skillman DR, Liao MJ, et al. Phase I trial of interferon alfa-n3 in early-stage HIV-1 disease. J-Immunother-Emphasis-Tumor-Immunol 1995;17116.

    PubMed
  80. Hassett J, Mendelsohn L. Effect of low dose oral interferon alfa-N3 in ARC. 9th-Int-Conf-AIDS 1993;I494.

    PubMed
  81. Friedman-Kien A. Management of condylomata acuminata with Alferon N injection, interferon alfa-n3 (human leukocyte derived). Am-J-Obstet-Gynecol 1995;1721359-1368.

    PubMed
  82. Fan SX, Skillman DR, Liao M-J, et al. Increased efficacy of human natural interferon alpha (IFN-alpha-n3) versus human recombinant IFN-alpha-2 for inhibition of HIV-1 replication in primary human monocytes. AIDS-Res-Hum-Retroviruses 1993;91115-1122.

    PubMed
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