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Ibalizumab - TaiMed Biologics

Drug Profile

Ibalizumab - TaiMed Biologics

Alternative Names: Hu1A8; Hu5A8; Ibalizumab-uiyk; TMB-355; TNX-355; Trogarzo

Latest Information Update: 20 Mar 2024

At a glance

  • Originator Biogen Idec
  • Developer TaiMed Biologics; Theratechnologies
  • Class Antiretrovirals; Monoclonal antibodies
  • Mechanism of Action HIV fusion inhibitors; Virus internalisation inhibitors
  • Orphan Drug Status

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

    Yes - HIV-1 infections
  • New Molecular Entity Yes
  • Available For Licensing Yes

Highest Development Phases

  • Marketed HIV-1 infections
  • Preclinical HIV-2 infections

Most Recent Events

  • 18 Mar 2024 Ibalizumab Commercialized to AcedrA BioPharmaceuticals in the Middle East and North Africa Region
  • 27 Feb 2024 Theratechnologies receives a refusal to file letter from the FDA for ibalizumab (Trogarzo®) in HIV-1 infections
  • 02 Jan 2024 Preregistration for HIV-1 infections (Treatment-experienced) in USA (IM)

Development Overview

Introduction

Ibalizumab is a humanised IgG4 monoclonal antibody, being developed by TaiMed Biologics, for the treatment of HIV-1 and HIV-2 infections. Ibalizumab inhibits HIV entry by binding to CD4 and preventing conformational changes in HIV gp120 that trigger co-receptor binding and membrane fusion. The drug is a long-acting antiretroviral, and CD4-directed post-attachment HIV-1 inhibitor. Ibalizumab binds to domain 2 of CD4 without blocking the interaction of HIV gp120 with domain 1 of CD4. Ibalizumab prevents entry of HIV into the cell and prevents its from infecting CD4+ immune cells while preserving normal immune function. Intravenous ibalizumab is available in the US, France, Netherlands, Poland, Italy and Germany. The drug is approved in the Puerto Rico, European Union, Iceland, Norway and Liechtenstein for the treatment of HIV-1 infections. The candidate is also approved in the US for IV push formulation. Intramuscular ibalizumab is under regulatory review in the US. Clinical development is underway in Taiwan for intravenous and intramuscular formulations of ibalizumab in HIV-1 infections. Preclinical development is underway in HIV-2 infections in France. Clinical development is underway in EU for intramuscular formulations of ibalizumab in HIV-1 infections. The intravenous formulations of the drug was under development in Canada which is discontinued. The subcutaneous formulations of the drug was under development in Canada however, no development has been reported as of March 2018.

Along with intravenous and intramuscular, the candidate is also developed in the formulation of IV Push, a more convenient form of administration, can be infused within 30 seconds without dilution compared to the 15-minute infusion time of the original IV Infusion. The IV push loading dose is approved in the US.

Tanox was originally developing the antibody, which was initially discovered by Biogen. TaiMed acquired the drug from Genentech (which had previously acquired Tanox).

As of April 2022, TaiMed Biologics is seeking marketing partnership for ibalizumab in the European Union [1] .

Company Agreements

In May 2024, TaiMed Biologics entered into a marketing agreement with AcedrA BioPharmaceuticals to commercialize Ibalizumab-uiyk (Trogarzo®) in the Middle East and North Africa Region. Under the terms of this agreement, AcedrA will be responsible in providing Trogarzo® in reply to named-patient requests through which physicians can legally and ethically prescribe Trogarzo® for patients prior to commercial availability. AcedrA, then, by a wider array of distribution activities, will be responsible for regulatory, sales, marketing, medical, and distribution in the MENA region.
[2]

In November 2022, TaiMed Biologics announced the termination of the exclusive commercialization rights for Trogarzo in European Territory with Theratechnologies as the recent price negotiations with key European countries were not satisfactory to Theratechnologies and the proposed reimbursed prices fall well below the floor price set by TaiMed, making it unfeasible to continue selling the drug in those countries. Theratechnologies continues to have the exclusive rights to commercialize Trogarzo in North American Territory. In April 2022, Theratechnologies sent a notice of termination to TaiMed which communicated their intention to cease commercialisation of ibalizumab (Trogarzo) in Europe, 180 days from April 27, 2022. Theratechnologies will return the European commercialization rights to TaiMed. The decision was taken due to unsatisfactory price negotiations with the European countries and receiving less than expected proposed reimbursed amount. Earlier in March 2017, TaiMed Biologics amended its agreement with Theratechnologies granting the latter commercialisation rights for ibalizumab additionally in the EU, Israel, Norway, Russia and Switzerland. The amended agreement also has a 12-year term following regulatory approval on a country-by-country basis. As per the terms of agreement the former will bear all regulatory responsibilities and associated costs. The latter will be responsible for any EMA required clinical trial and associated costs. Initial upfront payment of 906 077 Theratechnologies’ common shares equivalent to $US3 million was paid as an upfront payment by Theratechnologies. For sales up to $US50 million, transfer price of 52% will be paid which will increase to 57% if annual sales cross $US50 million threshold. TaiMed is eligible for an approval milestone payment of 50% of the cost of clinical trials and other development activities required for approval in Europe. A launch milestone payment of $US10 million is also payable with other milestone payments upon reaching certain threshold of net European sales over four consecutive quarters. Earlier, Theratechnologies and TaiMed Biologics entered into the 12-year collaboration agreement, in March 2016, for commercialisation of intravenous and intramuscular ibalizumab in the US and Canada. Under the terms of the agreement, Theratechnologies made a $US1 million cash payment and is obliged to make next $US1 million payment at the commercial launch. TaiMed Biologics is eligible for a further $US8.5 million payment due at commercial launch, subject to certain conditions, plus future development and sales milestone payments from Theratechnologies. TaiMed Biologics will be responsible for continued development, manufacture and supply of ibalizumab and regulatory approval in the US, while Theratechnologies will be responsible for regulatory approval in Canada. [3] [4] [1] [5]

In May 2021, TaiMed Biologics entered into an agreement with Theratechnologies to initiate a phase III study of ibalizumab (Trogarzo) intramuscular injection to further broaden the reach of ibalizumab to multidrug resistant (MDR) HIV-1 patients in USA and European union. Trial related costs and expenses will be paid by Theratechnologies which will have no effect on the profit sharing of their marketing agreement. [6]

In March 2020, TaiMed Biologics entered into a complete settlement agreement with Genentech for all disputes of the milestone and royalty payments. After fulfilling the agreed terms of settlement, the license agreement will be terminated, post which TaiMed have no obligation for any payments. In 2007, Genentech licensed ibalizumab to TaiMed Biologics [7]

In March 2020, TaiMed Biologics entered into a complete settlement agreement with Biogen for all disputes of the milestone and royalty payments. After fulfilling the agreed terms of settlement, the license agreement will be terminated, post which TaiMed have no obligation for any payments. In 1998, Tanox (a subsidiary of Genentech) in-licensed exclusive worldwide rights to ibalizumab from Biogen (now Biogen Idec), with limited sublicense rights. Tanox paid an upfront license fee, and was to make additional milestone payments up to an aggregate of $US10.4 million, of which, $US100 000 has been paid. Tanox was also to make royalty payments on annual net sales revenue. In November 2003, Biogen and IDEC Pharmaceuticals merged to form Biogen Idec [7]

In August 2012, TaiMed Biologics engaged WuXi PharmaTech in a contract manufacturing agreement for global phase II and III clinical trial supplies of subcutaneous ibalizumab [8] .

Key Development Milestones

TaiMed plans to implement the Post-Approval Named Patient Program (PA-NPP), to continue supplying Trogarzo in Europe and extends the PA-NPP to global regions outside of the United States and Canada. It will be announced by a company press release once the partner has been confirmed. After that, Taimed will evaluate the future drug use situation in Europe, and consider working with the commercial partner to re-market the drug by applying for a new dosage form of Trogarzo for intravenous or intramuscular injection [5] .

HIV-1 infections: Intravenous infusion formulation

Ibalizumab was launched in the US, in April 2018, for the treatment of human immunodeficiency virus type 1 (HIV-1) infection [9] . In March 2018, the US FDA approved ibalizumab (Trogarzo™) in combination with other antiretroviral treatments (ARTs) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen [10] [11] . The company is expecting to launch ibalizumab in the US by end of April 2018 [12] . The US FDA, in June 2017, accepted under the Priority Review status, TaiMed Biologics' BLA, seeking the approval of ibalizumab for the treatment of multi-drug resistant HIV-1 infection. The Prescription Drug User Fee Act (PDUFA) target action date had been set for January 03, 2018. However, in November 2017, the US FDA extended the PDUFA target action date to April 3, 2018. The additional time was required for a full review of the additional documents submitted by TaiMed, related to the manufacturing section of the BLA, as per FDA's request. The BLA was submitted in May 2017, and was supported by data from the phase III TMB-301 study [see below] [13] [14] [15] .

In May 2014, the US FDA approved the first batch of ibalizumab manufactured by WuXi PharmaTech for use in the treatment of patients with HIV-1 infections on expanded access. It will be used for continuing treatment of patients under investigator-sponsored INDs. WuXi PharmaTech reported that this was the first FDA approval of a sterile biologic manufactured in China for use under a US IND. TaiMed Biologics stated that the next phase of its collaboration with WuXi PharmaTech would be focussed on bringing the drug to marketing approval [16] .

As of June 2022, the ibalizumab is available in Netherlands, Poland and France. In September 2019, European Commission granted approval to ibalizumab (Trogarzo®) for the treatment of multi-drug resistant HIV-1 infections [17] . In April 2019, TaiMed Biologics announced that the Scientific Advisory Group HIV/Viral Diseases (SAG) of the Committee for Medicinal Products for Human use (CHMP) gave a positive recommendation to ibalizumab. In July 2019, the European Medicines Agency (EMA)’s human medicines committee (CHMP) granted a positive opinion for ibalizumab for the treatment of multi-drug resistant HIV-1 infections [18] [19] [20] .In February 2019, the European Medicines Agency (EMA) had completed the Pre-Approval Inspection (PAI) of WuXi Biologics' cGMP drug substance (DS) and drug product (DP) manufacturing facilities, for the production of ibalizumab without identifying any critical issues. WuXi Biologics intends to submit responses to the EMA inspection report in March 2019, and anticipates obtaining GMP certification for its facilities in May 2019. Moreover, WuXi PharmaTech reported that this was the first such inspection of its kind in China [21] . In September 2018, the EMA confirmed the validity of marketing authorization application for ibalizumab filed in late August 2018. The validation confirms the submission completion, and begins the EMA’s centralised review process, dated to start in September 2018. In July 2018, Theratechnologies reported decision of Committee for Medicinal Products for Human Use (CHMP)'s (of the EMA) for reviewing the marketing authorisation application (MAA) for ibalizumab under the accelerated assessment procedure, for the treatment of HIV-1 infections. The application was based on the same clinical trial data that was reviewed by the FDA to grant marketing authorization of ibalizumab in the US [22] [23] [24] .

In April 2018, Theratechnologies announced, following meetings with the Rapporteur and Co-Rapporteur countries as well as with representatives from the EMA, that it will seek regulatory approval from the EMA for ibalizumab using efficacy and safety data from the clinical trials submitted to the US FDA [25] . In March 2017, Theratechnologies announced its intention to initiate discussions with the EMA for potential submission of a regulatory application [4] .

In September 2020, Theratechnologies, through its subsidiary, Theratechnologies Europe Limited, launched ibalizumab (Trogarzo®) in Germany, for the treatment of adults infected with multidrug resistant human immunodeficiency virus type 1 (HIV-1) infections for whom it is otherwise not possible to construct a suppressive antiviral regimen, in combination with other antiretrovirals. Theratechnologies filed its health technology assessment for the drug with the German health authority, Gemeinsamer Bundesausschuss. The drug can be commercialised based on German regulations, while the file is being reviewed by the health authority [26] .

In October 2023, Theratechnologies announced that it is planning to seek expert advice prior to completing a regulatory submission of ibalizumab (Trogarzo®) IM administration maintenance dose to the U.S. Food and Drug Administration (FDA) [27] .

In November 2018, TaiMed Biologics and Westat completed an expanded access phase III trial that evaluated the safety and tolerability of ibalizumab IV combined with an optimised background regimen for the treatment of patients with multi-drug resistant HIV-1 infections (TMB-311; NCT02707861). Patients were enrolled in two cohort. The non-randomised, parallel, open-label trial was initiated in March 2016, and enrolled 79 patients in the USA and Puerto Rico. In March 2019, updated efficacy and safety data from the trial were released by Theratechnologies [28] [29] [30] [31] . In October 2019, efficacy data from the trial were presented at the ID Week (IDW-2019) [32] [33] . In November the company released updated efficacy data from the trial [34] . In October 2020, the company presented updated efficacy data from the trial at IDWeek 2020 (IDW-2020) [35] [36] .

In December 2016, TaiMed Biologics completed the phase III TMB-301 trial, which met the primary endpoint without any treatment-related serious adverse events or discontinuations being reported at day 14 (TMB-301; NCT02475629). The trial evaluated the safety and efficacy of ibalizumab, in combination with an optimised background regimen of antiretroviral medications, in treatment-experienced patients with multi-drug resistant HIV-1 infections. This open-label, 24-week trial initiated in August 2015 enrolled 40 patients in the US, Puerto Rico and Taiwan, with the last patient having entered the 7-day control period. The treatment phase of the study has been completed in October 2016 and the last patient was enrolled in April 2016. On completion of this phase III trial, the regulatory application will be evaluated under priority review by the US FDA [37] [38] [3] [39] [40] [41] . In October 2018, Theratechnologies released the additional analysis results of the phase III trial. In March 2019, updated efficacy and safety data from the trial were released by the company at the 26th Conference on Retroviruses and Opportunistic Infections (CROI-2019) [42] [29] [43] [44] [3] [45] [46] . In March 2020, the company presented efficacy data from the phase III TMB-301 trial in HIV-1 infections at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [47] .

A phase IIb randomised dose-response clinical trial has been conducted in the US and Puerto Rico (NCT00784147; TMB-202 Amendment 2). The trial enrolled 113 treatment-experienced patients infected with HIV-1. The 24-week trial assessed intravenous ibalizumab (800mg every 2 weeks or 2000mg every 4 weeks) plus an optimised background regimen. Results were reported in September 2011 [48] [49] . In December 2016, an investigator-sponsored extension of the TMB-202 study was completed in collaboration with TaiMed Biologics that investigated the efficacy of continued use of ibalizumab beyond the original 24 weeks, in patients who continue to demonstrate virologic response (5460; NCT01056393). The randomised, open-label trial was initiated in November 2009 and enrolled 5 patients in the US [50] .

In March 2008, Tanox completed a phase IIa clinical trial of intravenous ibalizumab with an optimised background regimen, in treatment-experienced HIV-1 infected patients (TNX-355.03; NCT00089700). The trial was initiated in March 2004 and enrolled 82 patients in the US, Canada, and Puerto Ricoreported [51] [52] [53] [54] .

In October 2003, the US FDA granted fast track status to ibalizumab for the treatment of patients with HIV-1 infection who have failed or are failing antiretroviral therapy. Ibalizumab was granted orphan drug status by the FDA in December 1993 [55] .

In October 2014, TaiMed Biologics received an orphan drug designation from the US FDA for ibalizumab in the treatment of HIV-1 infections [56] . The agent also received breakthrough therapy designation from the US FDA in February 2015 for the treatment of HIV-1 infections [57] .

Late-breaking data presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2006) showed that patients involved in a phase Ib trial treated with ibalizumab later developed HIV virus with phenotypic resistance to the drug. In vitro studies of sera from such patients revealed that while the mechanism of resistance development to ibalizumab has not been clearly elucidated, reduced susceptibility to ibalizumab does not appear to alter the CD4 requirement for HIV entry [58] .

A multiple-dose, 9-week phase Ib trial was completed successfully [59] .

Intravenous slow push formulation

In October 2022, Theratechnologies announced that the US FDA approved ibalizumab-uiyk (Trogarzo®) for administration by intravenous (IV) push method by which the undiluted medication is “pushed” by syringe for faster administration into the body’s circulation. The maintenance dose can be administered as an undiluted IV push over 30 seconds. The approval was based on study TMB-302 (see below) that showed that the safety and PK profile of ibalizumab-uiyk administered via IV push are similar to that of IV infusion administration [60] . In February 2022, Theratechnologies reported that the US FDA accepted the earlier submitted sBLA for the IV push form of administration of ibalizumab and assigned a target action date of October 3, 2022 as per the Prescription Drug User Fee Act (PDUFA). Earlier in December 2021, Theratechnologies submitted supplemental biologics license application (sBLA) to the US FDA for the IV push form of administration of ibalizumab for improving the lives and treatment outcomes for patients living with HIV infections. The submission was based on data from a phase III trial (See below) [61] [62] .

In October 2022, TaiMed Biologics completed a phase III trial that evaluated the safety and pharmacokinetics of ibalizumab (800mg) administered as undiluted IV push over 30 seconds in patients with HIV-1 infections, who had received stable ibalizumab regimen (NCT03913195; TMB-302). The open-label study was initiated in May 2019 and enrolled 46 patients in the US. In September 2021, Theratechnologies released results from the trial. In September 2021, TaiMed Biologics released results from the trial. In February 2022, the company presented updated data from the trial at the 29th Conference on Retroviruses and Opportunistic Infections (CROI-2022) [61] [63] [64] [65] [66] . In October 2023, updated efficacy and adverse events data from the trial were released by the company [27] .

In March 2019, Theratechnologies reported that the US FDA had authorised study protocol TMB-302, to evaluate an intravenous (IV) slow push formulation of Trogarzo® (ibalizumab) injection [67] .

Parenteral

In August 2018, the Paediatric Committee of the European Medicines Agency (EMA) deferred the initiation of the Paediatric Investigation Plan for ibalizumab (Trogarzo™) as the application for marketing authorisation had been filed with the EMA [68] . Company intends to evaluate ibalizumab in children aged 6 to <18 years old [69] .

Subcutaneous injection/Intramuscular injection formulation

In February 2024, Theratechnologies announced that the US FDA has issued a refusal to file letter (RTF) regarding the Company’s supplemental Biologics License Application (sBLA) for an intramuscular (IM) method of administration for the maintenance dose of ibalizumab (Trogarzo®). Upon preliminary review, the FDA determined that the sBLA was not sufficiently complete to permit a substantive review. The RTF states that the sBLA did not contain the data required to establish the pharmacokinetic bridge between the IM and the intravenous infusion route of administration of Trogarzo® [70] . In January 2024, Theratechnologies filed a supplemental Biologics License Application (sBLA) for an intramuscular (IM) method of administration every two weeks for the maintenance dose of ibalizumab to the US FDA for review. Theratechnologies expects acknowledgment letter of the sBLA application within 30 days along with a Prescription Drug User Fee Act (PDUFA) goal date [71] . In March 2016, TaiMed Biologics announced that it is developing subcutaneous and intramuscular formulations of ibalizumab to reduce the frequency of administration to bi-weekly or monthly. TaiMed Biologics announced its plan to conduct the trial of intramuscular or subcutaneous ibalizumab in a broad patient population with HIV-1 infections [3] .

In May 2021, TaiMed Biologics initiated a phase III clinical study of Trogarzo® (IM) for the treatment of patients with HIV-1-infections in the European union and the US [6] . In April 2022, TaiMed Biologics completed enrollment in the trial and is currently considering enrolling additional patients to further strength the clinical data set [72] [73] .

TaiMed Biologics is conducting a randomised phase I/II trial evaluating the pharmacodynamics and pharmacokinetics of intramuscularly (IM) administered ibalizumab in patients with HIV-1 infection who have not received antiretroviral treatment for at least one year in Taiwan (TMB-121). The pharmacodynamics and pharmacokinetics of ibalizumab IM was comparable with that of intravenously administered ibalizumab from a previous study. In February 2017, TaiMed Biologics presented pharmacokinetics, efficacy and safety data from the trial at the 24th conference on Retroviruses and Opportunistic Infections (CROI-2017) [74] [75] [76] .

TaiMed Biologics initiated a phase I/II trial of ibalizumab for subcutaneous and intramuscular administration in HIV negative volunteers and HIV patients in 2013 in Taiwan (TaiMed Biologics website, March 2016). The company was evaluating the intramuscular injection of ibalizumab for both bi-monthly and monthly administration as of March 2016 [3] . As of February 2022, Theratechnologies and TaiMed are evaluating an intramuscular (IM) mode of administration for Trogarzo® within the TMB-302 study [See above]. Patient screening for the IM study is in progress and completion is expected in the second half of 2022 [77] .

In September 2012, TaiMed Biologics, in collaboration with the Aaron Diamond AIDS Research Center and the Bill and Melinda Gates Foundation, completed a randomised, double-blind, placebo-controlled phase I trial of subcutaneous ibalizumab in sequentially increasing dose-groups, in at-risk, HIV-negative, healthy volunteers (TMB-108; NCT01292174). The trial was initiated in February 2011 and enrolment of 24 patients was completed in the US in May 2012 [78] .

TaiMed Biologics plans to conduct a phase II/III trial for front-line treatment of HIV infections in 2016 (TaimedBiologics pipeline, January 2016 and May 2016).

HIV-2 infections

In July 2020, in vitro antiviral data for ibalizumab was released by Theratechnologies in HIV-2 infections [79] .

Labelling information

In December 2023, the US FDA has approved the Labelling Prior Approval Supplement to include a 2000-mg intravenous (IV) push loading dose for ibalizumab. The label update follows FDA approval of the IV push maintenance dose in October 2022 [80] .

Financing information

In June 2018, Theratechnologies closed offering of convertible unsecured senior noted, which raised $US 57.5 millions. Theratechnologies intends to utilise the proceeds for payments totalling $US23,850,000 due under the third amendment of the EMD Serono termination agreement, an amount of approximately $US5,000,000 for approval and commercialisation of ibalizumab in the Europe. Rest of the proceeds will be utilised for general corporate purposes [81] .

Patent Information

The patents for ibalizumab expired in Europe, Canada, and Australia in 2011, and will expire in the US (US 05 871 732) in 2016, subject to extensions. The patent application is filed in Japan. The drug is covered under a worldwide patent WO 09 209 305.

Drug Properties & Chemical Synopsis

  • Route of administration IM, IV, Parenteral, SC
  • Formulation Infusion, Injection, unspecified
  • Class Antiretrovirals, Monoclonal antibodies
  • Target CD4 antigen; HIV fusion; Virus internalisation
  • Mechanism of Action HIV fusion inhibitors; Virus internalisation inhibitors
  • WHO ATC code

    J05A-X (Other antivirals)

  • EPhMRA code

    J5C4 (HIV antivirals, entry inhibitors)

  • Chemical name Immunoglobulin G4, anti-(human CD4 (antigen)) (human-mouse monoclonal 5A8 γ4-chain), disulfide with human-mouse monoclonal 5A8 κ-chain, dimer
  • CAS Registry Number 680188-33-4

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

HIV-1 infections

Detailed Description

T-cell surface antigen CD4

leptin receptor

1

1

HIV-1 infections

Eligibility Criteria

T-cell surface antigen CD4

2

HIV-1 infections

Outcome Measure

T-cell surface antigen CD4

protease, serine 33

IKAROS family zinc finger 4

EOS

2

1

1

1

Biomarker

Drug Name Biomarker Name Biomarker Function
Ibalizumab - TaiMed Biologics EOS Outcome Measure
IKAROS family zinc finger 4 Outcome Measure
Interferon Gamma (IFNg) Outcome Measure
Interleukin-10 (IL-10) Outcome Measure
Interleukin-2 (IL-2) Outcome Measure
Interleukin-6 (IL-6) Outcome Measure
Interleukin-8 (IL-8) Outcome Measure
leptin receptor Detailed Description
protease, serine 33 Outcome Measure
T-cell surface antigen CD4 Arm Group Description, Brief Title, Detailed Description, Eligibility Criteria, Official Title, Outcome Measure
Tumor necrosis factor alpha (TNF-alpha) Outcome Measure
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
HIV-1 infections - Combination therapy, Treatment-experienced Marketed USA IV / Infusion TaiMed Biologics 30 Apr 2018
HIV-1 infections - Combination therapy Marketed France, Germany, Italy, Netherlands, Poland IV / Infusion Theratechnologies 24 Feb 2022
HIV-1 infections administered as intravenous push formulation - Registered USA IV / Infusion TaiMed Biologics 03 Oct 2022
HIV-1 infections - Combination therapy Registered European Union, Iceland, Liechtenstein, Norway IV / Infusion Theratechnologies 26 Sep 2019
HIV-1 infections - Combination therapy, Treatment-experienced Registered Puerto Rico IV / Infusion TaiMed Biologics 07 Mar 2018
HIV-1 infections - Treatment-experienced Preregistration USA IM / Injection TaiMed Biologics 02 Jan 2024
HIV-1 infections - - Phase III European Union IM / Injection TaiMed Biologics 19 May 2021
HIV-1 infections - Treatment-experienced Phase III Taiwan IV / Infusion TaiMed Biologics 01 Aug 2015
HIV-1 infections - - Phase II Taiwan IM / Injection TaiMed Biologics 20 May 2016
HIV-1 infections - - No development reported (I/II) Taiwan SC / Injection TaiMed Biologics 08 Mar 2018
HIV-1 infections - Treatment-experienced Discontinued (II) Canada IV / Infusion TaiMed Biologics 08 Mar 2018
HIV-2 infections - - Preclinical France Parenteral / unspecified Theratechnologies 06 Jul 2020

Priority Development Status

Type Region Indication
Breakthrough Therapy USA HIV-1 infections

Orphan Status

Indication Patient Segment Country Organisation Event Date
HIV-1 infections - USA TaiMed Biologics 23 Oct 2014

Commercial Information

Involved Organisations

Organisation Involvement Countries
Biogen Idec Originator USA
Biogen Idec Owner USA
AcedrA BioPharmaceuticals Market Licensee Middle East, North Africa
Genentech Licensee World
TaiMed Biologics Sub-licensee World
Theratechnologies Sub-licensee Canada, USA

Licensing Availability

Licensing Organisation Available Indication Available Phase Region Date
TaiMed Biologics - Unspecified European Union 27 Apr 2022

Brand Names

Brand Name Organisations Indications Countries
Trogarzo Theratechnologies HIV-1 infections European Union, USA

Scientific Summary

  • Adverse Events Rare: Depression; Renal failure; Seizures

Pharmacokinetics

Updated results from a phase III TMB-302 trial showed that the proportion of patients with average C trough ≥ 300 ng/mL was observed to be 18/19 (94.7%) for both intravenous infusion (IVI) and IV push (IVP) and the 90% CI of the AUC ratio of IVP to IV Infusion was reported to be within the target value (0.9478- 1.1226). Among people with HIV (PWH), median VL at baseline and end of study was <20 copies/ mL, with no virologic failures observed. One patient experienced virologic rebound following the last IVP dose, which was linked to non-adherence to the oral antiretroviral regimen. Earlier results from a phase III TMB-302 trial showed that the proportion of patients with mean trough serum drug concentration equal or exceeding the target concentration was also the same for both forms of administration. The AUC values were comparable for both forms of administration. The p-value of the TOST was 0.0298. Both of the results showed that there were no differences in PK between IV push and IV infusion [64] [63] [65] [66] .

The pharmacokinetic profile of IM injection of ibalizumab at a dose of 800mg was comparable with IV infusion of the drug in a phase I/II trial conducted in patients with HIV-1 infection. The terminal half life was observed to be 0.86 day and distribution half life was 3.47 days with mean trough concentration of 5 to 14µg/ml. The randomised trial enrolled eight HIV positive male patients in 800mg dosing group who had not received antiretroviral (ARV) treatment for the preceding year [74] [76] .

Pharmacokinetic data from the phase III TMB-301 showed that high levels of CD4 receptor occupancy and drug concentration above therapeutic level was observed post injection of ibalizumab at a dose of 2,000 mg loading dose followed by an 800 mg maintenance dose every two weeks [39] .

Adverse Events

Updated data from the expanded access phase III TMB-311 trial, showed that ibalizumab (IBA) plus optimized background regimen (OBR) was well tolerated with a consistent safety profile as the pivotal phase III studies. During the follow-up period, there were no treatment-emergent adverse events (TEAE) or therapy discontinuations related to IBA. Earlier data showed that in the cohort 2 patients, diarrhoea (24%), headache (21%), nausea, cough, rash, and fatigue (16% each) were the most common adverse reactions. Injection site reactions related to the drug were not reported. Most events were mild in severity and Grade ≥3 TEAEs were reported in nine patients. An event of immune reconstitution inflammatory syndrome was reported that was considered possibly related to IBA. Two events were fatal (sepsis and cardiac arrest), however none were related to the drug. About 89% patients continued to receive treatment until week 48 and 3 patients discontinued early due to non ibalizumab-related reasons. No new or unexpected safety issues were observed between weeks 24 and 48. The trial enrolled a total of 79 patients [35] [32] [28] [29] [30] [31] .

The updated results from the phase III TMB-302 study demonstrated that ibalizumab was well tolerated in each subject received IM maintenance doses for eight weeks of treatment and a total of 152 IM injections. Injection-site pruritus (itching) was reported in one patient at a single time point. Injection-site pain was not observed in any patient who was administered with intramuscular ibalizumab [27] . Previous results from a phase III TMB-302 trial showed there were no serious adverse events observed and drug-related adverse events were considered mild to moderate. An adverse event was reported in the study which was related to the treatment. All AEs were considered to be mild to moderate. No notable safety signals were observed on clinical laboratory parameters. Adverse events reported were unrelated to IBA, consent withdrawal and protocol noncompliance [64] [61] [63] [65] [66] .

Ibalizumab was well tolerated through 96 weeks in the TMB-301 phase III trial conducted in patients with multi-drug resistant HIV-1 infections. The reasons for five discontinuations were death (2 patients) consent withdrawal (2 patients) and physician decision. All five reasons were non ibalizumab-related. Ibalizumab plus Optimized Background Regimen (OBR) was well tolerated with no new safety concerns emerging between week 25 and 96. For these 27 patients, median viral load (VL) reduction from baseline was 2.5 log10 at week 25 and 2.8 log10 at week 96 in the intent-to-treat-missing-equals-failure analysis. Results were reported from 40 patients [42] . A case of immune reconstitution inflammatory syndrome was reported with no other drug related serious adverse events. The severity of the most treatment related adverse events was mild to moderate. Anti-ibalizumab antibodies were not detected in blood samples of the patients. Nine patients (23%) discontinued the treatment which includes four non-drug related deaths, three withdrawals and two lost to follow up patients. This non-randomised, parallel, open-label trial enrolled 40 treatment-experienced patients [44] [37] [41] .

Clinical studies

ibalizumab (800mg q2w) and ibalizumab (2000mg q4w) were generally well tolerated in HIV-1 infected treatment-experienced patients also receiving optimised background therapy, in a randomised, 24-week phase IIb trial (n=113). Most adverse events were mild-to-moderate in severity and the most frequently reported included diarrhoea, nausea, headache and rash, with no significant difference between arms. No serious adverse events or discontinuations occurred [48] .

Ibalizumab was well tolerated in a phase II trial in 82 patients. No serious adverse events related to treatment were reported and discontinuation rates between treatment and placebo arms of the study were comparable [98] [51] [88]

Ibalizumab when administered as an IM injection, was safe and well tolerated in a phase I/II trial conducted in patients with HIV-1 infection, at a dose of 800mg without any adverse events, injection site reactions or treatment discontinuations. The randomised trial enrolled eight HIV positive male patients in 800mg dosing group who had not received antiretroviral (ARV) treatment for the preceding year [74] [76] .

In a phase Ia study involving 30 extensively pretreated patients, single doses of ibalizumab at 0.3, 1, 3, 10 and 25 mg/kg were administered by IV infusion to five cohorts of six patients. Ibalizumab was well tolerated, with no serious adverse events or immunogenicity observed [94] .

Ibalizumab was generally well tolerated and showed no depletion of CD4+ T-cells in a phase Ib study involving 22 patients on stable, failing HAART or no background therapy who received weekly or bi-weekly IV infusions of ibalizumab for 8 or 9 weeks. Serious adverse events noted were reocurrence of known depression, new-onset seizure after vaso-vagal reaction during phlebotomy, and acute renal failure with known renal insufficiency. Nineteen patients were randomised between two arms to receive IV infusions of ibalizumab either weekly or every 2 weeks, for 9 weeks. The two arms had dosing of 10 mg/kg/weekly and 6 mg/kg/every 2 weeks, after an initial 10 mg/kg dose. After completion of the first two arms, a third arm of three subjects was added at 25 mg/kg/every 2 weeks, for 8 weeks [93] [91] [92] .

Preclinical studies

safety studies in rhesus monkeys show that ibalizumab is safe and well tolerated. Ibalizumab was administered weekly at 5 mg/kg or 25 mg/kg, for 8 weeks [95] .

Pharmacodynamics

Summary

Clinical:

In a phase I/II trial conducted in patients with HIV-1 infection, ibalizumab showed the mean CD4 receptor occupancy of more than 80% during the dosing period of 800mg IM injection every two weeks. The randomised trial enrolled eight HIV positive male patients who had not received antiretroviral (ARV) treatment for the preceding year [74] [76] .

Preclinical studies

HIV envelopes were made resistant to enfuvirtide or ibalizumab using site directed mutagenesis. In vitro testing demonstrated that while the enfuvirtide-resistant envelopes exhibited a 11- to 32-fold reduction in susceptibility to enfuvirtide, the same envelopes had a < 2-fold reduction in susceptibility to ibalizumab. Envelopes rendered ibalizumab-resistant displayed a wild-type level of susceptibility to enfuvirtide at week 9. Cross-resistance induced by either inhibitor was not seen [85] .

Treatment with ibalizumab reduced viral load in macaque monkeys infected with simian immunodeficiency virus of macaques (SIVmac). Ibalizumab demonstrated selectivity in that it did not have immunosuppressive activity in healthy monkeys [96] .

Ibalizumab binds to both human T-cells and macrophages, but only to T-cells from rhesus monkeys. In this tissue cross-reactivity study, ibalizumab was evaluated on human (3 donors, 37 tissues) and rhesus monkeys (2 donors, 37 tissues). Highly identical staining patterns of ibalizumab in the two types of tissues support the use of rhesus monkeys as preclinical models. Ibalizumab induced antibodies in healthy rhesus monkeys, but not in chimpanzees. Also, ibalizumab did not cross-react with other tissues [95] .

In vitro

studies have been conducted using sera of HIV-infected patients from a phase Ib study who received ibalizumab and later developed virus with phenotypic resistance to ibalizumab. Results have shown that ibalizumab-resistant HIV requires CD4 for cell entry. The plateau phenotype for ibalizumab correlated with the saturation of CD4 molecules with ibalizumab. Finally, ibalizumab-resistant HIV was susceptible to inhibition by enfuvirtide [58] .

Antimicrobial Activity

Summary

HIV-1 subtype B viruses, isolated from entry inhibitor-naive patients, were susceptible to ibalizumab, independent of chemokine coreceptor tropism. IC50 values for viruses capable of infecting CCR5 and CXCR4 cells were 0.01-0.16 µg/mL and 0.07-0.23 µg/mL, respectively [87] .

Treatment with ibalizumab prevented HIV-1 primary clinical isolates infecting target cells in vitro.

Ibalizumab was active against CXCR4, CCR5, and dual/mixed topic viruses in vitro [89] .

In vitro

analysis in HIV-2 infections showed that ibalizumab inhibited viral replication in all seven HIV-2 isolates with IC50 ranging from 0.002 to 0.18 µg/mL while maximum percent inhibition (MPI) was below 80% in only two strains, between 80 and 90% in one stain and above 90% in four strains [79] .

Drug Interactions

Summary

Ibalizumab showed strong synergistic antiretroviral activity in combination with enfuvirtide in vitro [89] .

Therapeutic Trials

Updated results from the expanded access TMB-311 phase III trial in patients with multi-drug resistant HIV-1 infections, showed that for most patients, the durability of virologic response was maintained with minimal adjustments to the optimized background regimen (OBR). The baseline median viral load (VL) was 4.4 log10 copies/mL (c/mL) and CD4 count was 135 cells/mL for the 12 patients who moved into expanded access after completion of TMB 202. At the last visit, all 12 patients were suppressed (VL < 50 c/mL) and gained an average of 99 CD4 cells/mL relative to baseline. Overall, the 12 patients remained on ibalizumab (IBA) for an average of 8.9 years (range 8-9.5), during which addition of new ARVs to their OBR was not needed in eight of 12 patients to maintain suppression. Earlier data showed that median baseline viral load (VL) and CD4 count were 35,350 copies/mL and 73 cells/mL, respectively. The number of patients in the VL strata were 11, 17 and 12 for VL of 10,000, 10,000-70,000, and 70,000 copies/mL, respectively. There were 12, 10, 5 and 13 patients in the subgroups with CD4 count 10, 10-100, 100-200 and 200 cells/µL. Population disease severity was reflected by four deaths. The proportion of suppressed patients increased from 55% at week 24 (n=31) to 75% for patients remaining on treatment for 96 weeks (n=20). Median VL decrease was 2.9 log10 copies/mL. Notably, no statistically significant differences were found across groups. Among patients with advanced HIV disease, 66.7% with CD4 count of 10 cells/mL and 71.4% with VL of 70,000 copies/mL at baseline remained fully suppressed at week 96.The efficacy results observed at week 25 were maintained until week 96. At time of last visit, all 12 patients reported undetectable viral load. Viral load suppression was reported in close to 60% of patients(16/27), who had participated in the TMB-301. About 56% of the patients achieved viral suppression below 50 copies/mL at both week 25 and week 96. At week 96, the median viral load reduction was 2.8 log10 compared with 2.5 log10 at week 25. An increase in the median CD4+ cell count increase was observed with 45 cells/µL at week 96 versus 42 cells/µL at week 25. Earlier it was reported that sustained virologic suppression was observed through 24 week till 48th week in 27 patients with multidrug resistant HIV-1. Median viral load reduction from baseline was 2.5log10 at weeks 24 and 48. All 15 patients with an undetectable viral load at week 24 maintained suppression to week 48. Another patient reached less than 50 copies/ml at week 48 after having a detectable viral load at week 24. 63% patients achieved a viral load less than 200 copies/ml. At baseline, TMB-311 trial had, a median viral load of 21 700 copies/mL. 19% of patients had a viral load =100 000 copies/mL. The median CD4+ cell count was 102 cells/µL. In cohort 2, which enrolled 38 patients, ibalizumab treatment demonstrated the median viral load reduction of -2.6 log10 copies/mL at both 24 and 48 weeks. At week 24, 46% of patients taking ibalizumab reached a viral load reduction below 50 copies/mL and at week 48, 47% of patients taking ibalizumab reached a viral load reduction below 50 copies/mL. The trial enrolled a total of 79 patients [35] [35] [36] [34] [33] [29] [30] [31] .

The updated results from the phase III TMB-302 study demonstrated that the mean trough concentrations of ibalizumab was found to be greater than 15 µg/mL suggesting that IM injection was sufficient at maintaining the drug trough concentration above the therapeutic level of 0.3 µg/mL. In HIV patients, mean trough concentrations were comparable between IV infusion and IM injection. The trial did not meet the equivalence limits (0.8, 1.25) which is a primary endpoint measuring a 90% confidence interval of the ratio of IM injection to IV infusion (0.69, 1.08). The secondary endpoint, viral suppression was maintained in all HIV-positive subjects throughout the IM phase and the overall study [27] . Previous results from a phase III TMB-302 trial showed that the primary endpoint measuring a 90% confidence interval of the ratio of IV push to IV infusion was 0.9478-1.1226 which was within the target value. The proportion of patients with mean trough serum drug concentration equal or exceeding the target concentration was 18/19 (94.7%) for both forms of administration. Secondary endpoints were also achieved confirming no difference in HIV-1 viral load due to the change from IV infusion to IV push. Results showed that there were no increase in plasma viral load levels above thousand copies per ml on two consecutive measurements at least two weeks apart. Additionally, there were no anti-ibalizumab antibodies or immunogenicity concerns of ibalizumab detected [61] [63] [65] [66] .

In the phase III TMB-301 trial, treatment with ibalizumab demonstrated median viral load (VL) and CD4 counts of 65 000 and 20 000 copies/mL and 57 and 89 cells/mm3 for the OSS1 and OSS2 patients, respectively. In OSS1 (n=12) patients, 11 (92%) patients reported >0.5log10 VL decrease on IBA functional after 7 days. At Week 25, 5 of the 7 OSS1 patients reported <50 copies/mL, of which three were on fully active DTG. At Week 96, 5 of 7 OSS1 patients maintained viral suppression. In OSS2 patients, 13 of 18 patients reported a >0.5log10 VL decrease. At Week 25, 9 patients with OSS2 reported <50 copies/mL, 7 of which were on a fully active DTG regimen, with a similar virologic efficacy as IBA paired with one or two fully active agents. At Week 96, viral suppression was maintained in 9 patients [47] . Earlier results reported that ibalizumab was effective and maintained through 96 weeks. Dolutegravir was observed in 45% patients of which 11 had major dolutegravir resistance mutations (Q148 plus additional mutations). Of 18 dolutegravir resistant patients, 10 received dolutegravir in their optimised background regimen (OBR) while 16 of 22 dolutegravir susceptible patients received dolutegravir as OBR. Twenty-seven patients (68%) had darunavir resistance. Darunavir was included as OBR in 26 patients: 18 with darunavir resistant HIV and 8 with darunavir susceptible HIV. Long-term results were obtained for 27 patients of which 82% completed treatment up to 96 weeks. Results were reported from 40 patients enrolled in the study [42] . At week 48, the median viral load reduction was observed to be 2.9 log10 among the 24 patients who were still on treatment. Among those 24 patients, 67% (16 of 24) had a viral load under 50 copies/ml compared with a 2.8 log10 reduction and 59% of patients with a viral load suppression below 50 copies/ml with the ITT-MEF method. Earlier at day 14, a viral load reduction of at least 0.5 log10, was achieved by 83% of patients (33/40) treated with ibalizumab compared with 3% of patients in the control group. After 24 weeks of treatment, the mean reduction in viral load was 1.6 log10 and 48% of patients had a reduction in viral load of more than 2.0 log10. At the end of the treatment period, 43% (mean viral load reduction of 3.1 log10) of participants had undetectable viral load (HIV-1 <50 copies/mL), and 50% of patients had a viral load lower than 200 copies/mL. An increase in the total CD4+ T cell count of 9 cells/µL for lower than 50 cells/µL baseline level (n=17), 75 cells/µL for 50 to 200 cells/µL level (n=10) and 78 cells/µL for higher than 200 cells/µL level (n=13) was observed. Patients who did not achieve the primary endpoint of a 0.5 log10 viral load reduction, following seven days of receiving a loading dose of ibalizumab, consequently experienced clinical benefits during the length of the study. Three of the seven patients, after receipt of a loading dose after seven days, displayed a viral load under 50 copies/ml, or below detection, by week 25 in combination with an optimised background regimen. Another patient displayed a 1.1 log10 reduction in viral load by week 25, and viral load declined by 2.1 log10 and 1.6 log10 in two patients, respectively at week 21. One patient who did not complete the trial in this group showed a 0.5 log10 reduction in viral load, at day 21. Updated results showed that ibalizumab maintained viral suppression at week 25. About 44% of patients who were resistant to DTG achieved a viral load reduction >0.5 log10 from baseline at week 25, while 82% of DTG susceptible patients reached the same reduction level. In DRV resistant patients, 67% of patients achieved a viral load reduction >0.5 log10 from baseline while 62% of DRV susceptible patients reached the same reduction level. Earlier it was reported that at week 25, 31 of 40 patients had the median viral load reduction of 2.5 log10 with 55% (17 of 31) achieving a viral load below 50 copies/ml compared with a 1.8 log10 viral load reduction and 43% of patients with a viral load suppression below 50 copies/ml using the intent to treat missing equals failure (ITT-MEF) analysis method. The trial was conducted in 40 patients [29] [43] [40] [44] [45] [99] [46] [41] [100] .

Preliminary results demonstrated that 82.5% patients (33/40, p < 0.0001) met the primary endpoint during a phase III trial in patients with multi-drug resistant HIV-1 infections. A decrease of = 0.5 log10 in viral load was observed, following a 7-day treatment period with ibalizumab. This open-label, 24-week trial enrolled 36 patients [37] [41] .

At week 24, ibalizumab (800mg q2w) and ibalizumab (2000mg q4w) were associated with clinically relevant reductions in viral load in HIV-1 infected treatment-experienced patients also receiving optimised background therapy, in a phase IIb trial in 113 patients. The proportions of patients achieving viral loads <50 copies/mL were similar between treatment arms (44% vs 28% of patients; primary endpoint) [48] .

Ibalizumab, in combination with optimised background therapy (OBT), produced a significantly greater reduction in viral load compared with placebo + OBT, the primary endpoint for this phase II trial, in 82 patients with HIV at 24 and 48 weeks. Patients were randomised to receive ibalizumab (10 or 15 mg/kg) or placebo with OBT every two weeks. Patients in the 10 mg/kg group received a loading dose of 10 mg/kg every week for 8 weeks. After 48 weeks of treatment, patients who received 10 mg/kg and 15 mg/kg doses of ibalizumab had significantly greater reductions in viral load (0.82 log10 and 0.57 log10, respectively), compared with placebo recipients. A viral load reduction of at least 1 log10 was seen 37% patients in the ibalizumab 10 mg/kg arm, and 32% of those in the 15 mg/kg arm compared with 11% of the placebo group. The median time to loss of virologic response was significantly longer in those receiving either ibalizumab 10 mg/kg (230 days) or 15 mg/kg (253 days) compared with placebo group (0 days). Furthermore, patients who received v experienced significantly greater increases in CD4+ cell count, compared with placebo recipients. After 24 weeks of treatment with 10 mg/kg, the viral load reduction was 1.16 log10, compared with a reduction of 0.20 log10 in the placebo group. The maximum reduction in viral load observed during the 24-week trial period was 1.97 log10 in the 10 mg/kg group. In this group, 56% of patients achieved a reduction in viral load of at least 0.5 log10 at week 24, and 44% of patients had a reduction of at least 1.0 log10 at week 24. Treatment with 15 mg/kd resulted in a significant reduction in viral load of 0.95 log10. At week 24, 22% of patients receiving 10 mg/kg of ibalizumab had a viral load <400 copies/mL, compared with 0% of patients receiving placebo [98] [86] [101] [51] [90] [88] .

In a phase I/II trial conducted in patients with HIV-1 infection, IM injection of ibalizumab showed a mean maximum viral load reduction of 1.23 log10 at day seven which returned to the baseline of 55 000 copies /mL at the end of the dosing cycle. Average CD4+ T cell counts were observed to be 51% higher than the baseline (314 cells/µl) after three doses. The randomised trial enrolled eight HIV positive male patients in 800mg dosing group who had not received antiretroviral (ARV) treatment for the preceding year [74] [76] .

Treatment with ibalizumab significantly reduced HIV RNA levels in a phase Ia study involving 30 extensively pretreated patients. Single doses of ibalizumab at 0.3, 1, 3, 10 and 25 mg/kg were administered by intravenous (IV) infusion to five cohorts of six patients. Dose-dependent reductions in viral loads were observed, with the achievement of trough viral loads correlating with the duration of CD4+ cell coating. CD4+ cell depletion did not occur at any ibalizumab dose level [94] .

Ibalizumab therapy was associated with initial, clinically meaningful reductions in viral load in a phase Ib trial involving 22 patients with HIV-1 infection on stable, failing highly active anti-retroviral therapy (HAART) or no background therapy. Nineteen patients were randomised between two arms to receive IV infusions of ibalizumab either weekly or every 2 weeks, for 9 weeks. The two arms had dosing of 10 mg/kg/weekly and 6 mg/kg/every 2 weeks, after an initial 10 mg/kg dose. After completion of the first two arms, a third arm of three subjects was added at 25 mg/kg/every 2 weeks, for 8 weeks. Clinically relevant reductions from baseline in HIV-1 RNA levels of 0.5-1.7 log10 were seen in 21 of 22 patients; a 1 log10 decrease corresponds to a 90% reduction in viral load. By week 2, mean peak reductions from baseline in viral loads were 0.99 log10 with the 10 mg/kg/weekly dose, 1.11 log10 with the 6 mg/kg/bi-weekly dose, and 0.96 log10 with the 25 mg/kg/bi-weekly dose. Approximately two-thirds of the patients experienced reductions in viral loads of > 90%; four patients experienced a decrease from 5000 copies/mL at baseline, to 400 copies/mL. A return towards baseline viral loads by week 9 was associated with reduced susceptibility (increase in IC50) to ibalizumab. Recovery in viral load was associated with in vitro sensitivity to ibalizumab [93] [91] [92] .

Future Events

Expected Date Event Type Description Updated
02 Feb 2024 Regulatory Status Theratechnologies expects to receive an acknowledgment letter of the sBLA application along with a Prescription Drug User Fee Act (PDUFA) goal date within 30 days [71] 04 Jan 2024
31 Dec 2023 Regulatory Status Theratechnologies plans to file a sBLA to the US FDA for Ibalizumab for the treatment of HIV-1 infections (Intramuscular) in 2023 [82] 04 Jan 2024
03 Oct 2022 Regulatory Status US FDA assigns PDUFA action date of 03/10/2022 for ibalizumab for HIV-1 infections (Intravenous push formulation) [61] 05 Oct 2022
31 Dec 2021 Trial Update Theratechnologies plans a phase III trial for HIV-1 infection (IM) in 2021 (700269404) [69] 30 Dec 2021
31 Dec 2021 Regulatory Status Theratechnologies intends to initiate first study in paediatric investigation plan for HIV infections in second half of 2021 [69] 06 Mar 2021
31 Dec 2021 Regulatory Status Theratechnologies announces intention to submit supplemental Biologics License Application (sBLA) to US FDA for in fourth quarter of 2021 [65] 30 Dec 2021
29 May 2019 Regulatory Status CHMP plans to give recommendation for ibalizumab to the EMA in May 2019 (9265174) 31 Jul 2019
30 Sep 2018 Regulatory Status Theratechnologies intends to file for ibalizumab's regulatory approval from the EMA in HIV-1 infections in Europe around the end of 3Q 2018 [84] 02 Aug 2018
30 Apr 2018 Regulatory Status Theratechnologies plans to launch ibalizumab in USA in April 2018 [12] 11 Jul 2018
01 Apr 2018 Regulatory Status FDA assigns PDUFA action date of 03/04/2018 for ibalizumab for HIV-1 infections (Treatment experienced) (IV) [13] 07 Mar 2018
31 Mar 2017 Regulatory Status TaiMed Biologics announces intention to submit BLA to the US FDA in March 2017 09 May 2017

Development History

Event Date Update Type Comment
18 Mar 2024 Licensing Status Ibalizumab Commercialized to AcedrA BioPharmaceuticals in the Middle East and North Africa Region [2] Updated 20 Mar 2024
27 Feb 2024 Regulatory Status Theratechnologies receives a refusal to file letter from the FDA for ibalizumab (Trogarzo®) in HIV-1 infections [70] Updated 05 Mar 2024
02 Jan 2024 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-experienced) in USA (IM) [71] Updated 04 Jan 2024
02 Jan 2024 Regulatory Status Theratechnologies expects to receive an acknowledgment letter of the sBLA application along with a Prescription Drug User Fee Act (PDUFA) goal date within 30 days [71] Updated 04 Jan 2024
13 Dec 2023 Regulatory Status The US FDA approves ibalizumab (IV push formulation) for HIV1-infection in the USA [80] Updated 15 Dec 2023
13 Oct 2023 Regulatory Status Theratechnologies plans a regulatory submission of maintenance dose of Ibalizumab for the treatment of HIV-1 infections (IM) to the US FDA [27] Updated 17 Oct 2023
13 Oct 2023 Scientific Update Efficacy and adverse events data from a TMB-302 phase III trial in HIV infections released by Theratechnologies [27] Updated 17 Oct 2023
28 Feb 2023 Regulatory Status Theratechnologies plans to file a sBLA to the US FDA for Ibalizumab for the treatment of HIV-1 infections (Intramuscular) in 2023 [82] Updated 04 Jan 2024
01 Nov 2022 Regulatory Status TaiMed plans to implement the Post-Approval Named Patient Program (PA-NPP), to continue supplying Trogarzo in Europe and extends the PA-NPP to global regions outside of the United States and Canada [5] Updated 23 Nov 2022
01 Nov 2022 Company Involvement TaiMed Biologics terminates the exclusive commercialization rights for Trogarzo in European Territory and its neighboring countries such as the United Kingdom, Israel, Norway, Russia and Switzerland with Theratechnologies [5] Updated 15 Nov 2022
31 Oct 2022 Trial Update TaiMed Biologics completes a phase III trial in HIV-1 infections (Intravenous push formulation) in USA (IV) (NCT03913195) Updated 13 Oct 2021
03 Oct 2022 Phase Change - Registered Registered for HIV-1 infections in USA (IV) [60] Updated 05 Oct 2022
27 Apr 2022 Licensing Status Ibalizumab - TaiMed Biologics is available for market licensing in European Union as of 27 Apr 2022. www.taimedbiologics.com Updated 04 May 2022
27 Apr 2022 Licensing Status Theratechnologies sends notification of returning commercialization rights of ibalizumab in the European Union to TaiMed Biologics [1] Updated 04 May 2022
24 Feb 2022 Phase Change - Marketed Launched for HIV-1 infections (Combination therapy) in Italy (IV) [77] Updated 16 Mar 2022
16 Feb 2022 Regulatory Status US FDA assigns PDUFA action date of 03/10/2022 for ibalizumab for HIV-1 infections (Intravenous push formulation) [61] Updated 05 Oct 2022
12 Feb 2022 Scientific Update Updated pharmacokinetics and adverse events data from the TMB-302 phase III study in HIV infections were presented at the 29th Conference on Retroviruses and Opportunistic Infections (CROI-2022) [64] Updated 29 Mar 2022
07 Feb 2022 Trial Update TaiMed Biologics re-initiates a phase III trial in HIV-1 infections (Intravenous push formulation) in USA (IV) (NCT03913195) Updated 07 Feb 2022
06 Dec 2021 Phase Change - Preregistration Preregistration for HIV-1 infections in USA (IV Push formulation) [62] Updated 08 Dec 2021
04 Dec 2021 Regulatory Status TaiMed Biologics intends to obtain marketing approval in HIV-1 infections in Israel (IV, fusion) [83] Updated 30 Dec 2021
27 Sep 2021 Scientific Update Efficacy, pharmacodynamics and adverse events data from a phase III trial in HIV-1-infections released by TaiMed Biologics [63] [61] Updated 27 Sep 2021
22 Sep 2021 Regulatory Status Theratechnologies announces intention to submit supplemental Biologics License Application (sBLA) to US FDA for in fourth quarter of 2021 [65] Updated 30 Dec 2021
22 Sep 2021 Scientific Update Efficacy, adverse events and pharmacokinetic data from a phase III trial in HIV-1 infections released by Theratechnologies [65] Updated 24 Sep 2021
24 Jun 2021 Biomarker Update Biomarkers information updated Updated 17 Sep 2021
14 Jun 2021 Phase Change - Marketed Launched for HIV-1 infections (Combination therapy) in Netherlands, Poland, France (IV) Updated 03 Mar 2023
19 May 2021 Phase Change - III Phase-III clinical trials in HIV-1 infections in USA and European Union (IM), prior to May 2021 [6] Updated 31 Aug 2022
18 May 2021 Licensing Status TaiMed Biologics and Theratechnologies partner to initiate phase III trial of ibalizumab for HIV-1 infection (IM) in [6] Updated 27 May 2021
25 Feb 2021 Trial Update Theratechnologies plans a phase III trial for HIV-1 infection (IM) in 2021 [69] Updated 30 Dec 2021
25 Feb 2021 Regulatory Status Theratechnologies intends to initiate first study in paediatric investigation plan for HIV infections in second half of 2021 [69] Updated 06 Mar 2021
09 Dec 2020 Scientific Update Updated efficacy data from the phase III TMB-311 trial in HIV-infections presented at the IDWeek (IDW-2020) [36] Updated 09 Dec 2020
21 Oct 2020 Scientific Update Updated efficacy and adverse events data from the phase III TMB-311 trial in HIV-1 infections presented at the IDWeek 2020 (IDW-2020) [35] Updated 11 Dec 2020
11 Sep 2020 Phase Change - Marketed Launched for HIV-1 infections (Combination therapy) in Germany (IV) [26] Updated 13 Sep 2020
06 Jul 2020 Phase Change - Preclinical Preclinical trials in HIV-2 infections in France (Parenteral) before July 2020 [79] Updated 08 Jul 2020
06 Jul 2020 Scientific Update Antimicrobial data from a preclinical study in HIV-2 infections released by Theratechnologies [79] Updated 08 Jul 2020
11 Mar 2020 Licensing Status TaiMed Biologics enters a settlement agreement with Genentech and Biogen for milestone and royalty payments of Ibalizumab [7] Updated 17 Mar 2020
08 Mar 2020 Scientific Update Efficacy data from the phase III TMB-301 trial in HIV-1 infections presented at the 27th Conference on Retroviruses and Opportunistic Infections (CROI-2020) [47] Updated 05 Apr 2020
07 Nov 2019 Scientific Update Updated efficacy data from the phase III TMB-311 trial in HIV-infections released by Theratechnologies [34] Updated 21 Nov 2019
03 Oct 2019 Scientific Update Updated efficacy and adverse events data from phase III TMB-311 trials in HIV-infections released by Theratechnologies [33] Updated 10 Oct 2019
02 Oct 2019 Scientific Update Updated adverse events data from the phase III TMB-311 trial in HIV-infections presented at the IDWeek (IDW-2019) [32] Updated 30 Dec 2019
26 Sep 2019 Phase Change - Registered Registered for HIV-1 infections (Combination therapy) in European Union, Iceland, Liechtenstein, Norway (IV) [17] Updated 30 Sep 2019
25 Jul 2019 Regulatory Status The Committee for Medicinal Products for Human Use recommends approval of ibalizumab for HIV-1 infections in European Union [18] Updated 31 Jul 2019
30 May 2019 Phase Change - III Phase-III clinical trials in HIV-1 infections (Intravenous push formulation) in USA (IV) (NCT03913195) Updated 17 Jun 2019
17 Apr 2019 Regulatory Status CHMP plans to give recommendation for ibalizumab to the EMA in May 2019 [19] Updated 31 Jul 2019
17 Apr 2019 Regulatory Status Scientific Advisory Group (SAG) of CHMP gives a positive recommendation for ibalizumab [19] Updated 22 Apr 2019
08 Mar 2019 Scientific Update Updated efficacy and adverse events data from phase III TMB-301 and TMB-311 trials in HIV-infections released by Theratechnologies [29] Updated 13 Mar 2019
07 Mar 2019 Regulatory Status 9261936- updated KDM, HE, profile recently reviewed Updated 07 Mar 2019
06 Mar 2019 Regulatory Status CHMP recommends its Scientific Advisory Group (SAG) to review regulatory filing for ibalizumab [20] Updated 08 Mar 2019
04 Mar 2019 Scientific Update Updated efficacy and adverse events data from the TMB-301 phase III study in HIV infections were presented at the 26th Conference on Retroviruses and Opportunistic Infections (CROI-2019) [42] Updated 06 May 2019
04 Mar 2019 Trial Update Theratechnologies plans the TMB-302 clinical trial for HIV-1 infections (IV slow push formulation) [67] Updated 07 Mar 2019
01 Nov 2018 Trial Update TaiMed Biologics and Westat completes an expanded access phase III trial for HIV-1 infections (Combination therapy, Treatment-experienced) in Puerto Rico and USA (IV) (NCT02707861) Updated 30 Nov 2018
31 Oct 2018 Scientific Update Updated efficacy data from a phase III trial in HIV-1 infections (Treatment-experienced) released by Theratechnologies [43] Updated 09 Nov 2018
30 Oct 2018 Scientific Update Updated efficacy data from a phase III trial in HIV-1 infections released by Theratechnologies [40] Updated 06 Nov 2018
03 Oct 2018 Scientific Update Pharmacokinetics data from a phase III TMB-301 trial in HIV-1 infections presented at the IDWeek 2018 (IDW - 2018) Updated 09 Oct 2018
14 Sep 2018 Regulatory Status European Medicines Agency (EMA) accepts marketing authorization application of ibalizumab for the review [22] Updated 20 Sep 2018
20 Aug 2018 Regulatory Status Paediatric Committee of the European Medicines Agency defers the initiation of Paediatric Investigation Plan for Human immunodeficiency virus type 1 (HIV-1) infection [68] Updated 22 Aug 2018
20 Aug 2018 Regulatory Status Theratechnologies announces intention to launch ibalizumab in the Europe [68] Updated 22 Aug 2018
31 Jul 2018 Phase Change - Preregistration Preregistration for HIV-1 infections in European Union before July 2018 (IV) [24] Updated 02 Aug 2018
31 Jul 2018 Regulatory Status Ibalizumab receives accelerated assessment status in European Union for HIV-1 infections [24] Updated 02 Aug 2018
30 Apr 2018 Phase Change - Marketed Launched for HIV-1 infections (Combination therapy, Treatment-experienced) in USA (IV) [9] Updated 03 May 2018
24 Apr 2018 Regulatory Status Theratechnologies intends to file for ibalizumab's regulatory approval from the EMA in HIV-1 infections in Europe around the end of 3Q 2018 [84] Updated 02 Aug 2018
08 Mar 2018 Phase Change - Discontinued(II) Discontinued - Phase-II for HIV-1 infections (Treatment-experienced) in Canada (IV) Updated 08 Mar 2018
08 Mar 2018 Phase Change - No development reported(I/II) No development reported - Phase-I/II for HIV-1 infections in Taiwan (SC) Updated 08 Mar 2018
06 Mar 2018 Regulatory Status Theratechnologies plans to launch ibalizumab in USA in April 2018 [12] Updated 11 Jul 2018
06 Mar 2018 Phase Change - Registered Registered for HIV-1 infections (Treatment-experienced, Combination therapy) in USA and Puerto Rico (IV) - First global approval [11] Updated 07 Mar 2018
13 Nov 2017 Regulatory Status FDA assigns PDUFA action date of 03/04/2018 for ibalizumab for HIV-1 infections (Treatment experienced) (IV) [13] Updated 07 Mar 2018
04 Oct 2017 Scientific Update Safety and efficacy data from the phase III TMB-311 trial in HIV-1 infections released by Theratechnologies [30] Updated 06 Oct 2017
30 Jun 2017 Regulatory Status The US FDA accepts the BLA for ibalizumab for HIV-1 infections for priority review [14] Updated 04 Jul 2017
03 May 2017 Phase Change - Preregistration Preregistration for HIV-1 infections (Treatment-experienced) in USA (IV) [15] Updated 09 May 2017
03 May 2017 Regulatory Status TaiMed Biologics requests priority review status for ibalizumab for HIV-1 infections in USA [15] Updated 09 May 2017
06 Mar 2017 Licensing Status Theratechnologies acquires commercial rights to ibalizumab from TaiMed Biologics in European Union, Israel, Norway, Russia and Switzerland [4] Updated 08 Mar 2017
06 Mar 2017 Regulatory Status Theratechnologies announces intention to initiate discussion to submit a MAA with the EMA [4] Updated 08 Mar 2017
23 Feb 2017 Regulatory Status TaiMed Biologics announces intention to submit BLA to the US FDA in March 2017 Updated 09 May 2017
15 Feb 2017 Trial Update TaiMed Biologics initiates enrolment in a phase I/II trial for HIV-1 infections in Taiwan before February 2017 [75] Updated 21 Feb 2017
14 Feb 2017 Scientific Update Efficay and adverse events data from phase III TMB-301 trial in HIV-1 infections (Treatment-experienced) released by Theratechnologies [44] Updated 17 Feb 2017
13 Feb 2017 Scientific Update Efficacy, adverse events, pharmacokinetics and pharmacodynamics data from a phase I/II trial in HIV-1 infections presented at the 24th Conference on Retroviruses and Opportunistic Infections (CROI-2017) [74] Updated 23 Mar 2017
15 Dec 2016 Trial Update TaiMed Biologics completes an Investigator-sponsored phase II extension trial in HIV-1 infections in USA (NCT01056393) Updated 21 Aug 2017
01 Dec 2016 Trial Update TaiMed Biologics completes a phase III trial in HIV-1 infections (Treatment-experienced) in USA, Puerto Rico and Taiwan (IV) (NCT02475629) Updated 14 Feb 2017
26 Oct 2016 Scientific Update Efficacy data from a phase III trial in HIV-1 infections presented at the IDWeek 2016 (IDW - 2016) [45] Updated 02 Jan 2017
26 Oct 2016 Scientific Update Efficacy data from a phase III trial in HIV-1 infections released by Theratechnologies [46] Updated 26 Oct 2016
24 May 2016 Scientific Update Efficacy and adverse events data from a phase III trial in HIV-1 infections released by Theratechnologies [37] Updated 30 May 2016
20 May 2016 Phase Change - II Phase-II clinical trials in HIV-1 infections in Taiwan (IM) (TaiMed Biologics pipeline, May 2016) Updated 05 Jul 2016
27 Apr 2016 Trial Update TaiMed Biologics completes enrolment in a phase III trial for HIV-1 infections (Treatment-experienced) in USA, Puerto Rico and Taiwan [38] Updated 29 Apr 2016
18 Mar 2016 Active Status Review Ibalizumab is still in phase I/II trials for HIV-1 infections in Taiwan (IM) [3] Updated 29 Mar 2016
18 Mar 2016 Licensing Status Theratechnologies and TaiMed Biologics agree to co-promote Ibalizumab in USA and Canada for HIV-1 infections (IV),(IM) [3] Updated 29 Mar 2016
18 Mar 2016 Trial Update TaiMed Biologics plans a phase III trial for HIV-1 infections (SC),(IM) [3] Updated 29 Mar 2016
01 Mar 2016 Trial Update TaiMed Biologics and Westat initiates an expanded access phase III trial for HIV-1 infections (Combination therapy, Treatment-experienced) in Puerto Rico (IV) (NCT02707861) Updated 30 Nov 2018
01 Mar 2016 Trial Update TaiMed Biologics and Westat initiates an expanded access phase III trial for HIV-1 infections (Combination therapy, Treatment-experienced) in USA (IV) (NCT02707861) Updated 15 Mar 2016
18 Jan 2016 Trial Update TaiMed Biologics plans a phase II/III trial for HIV infections (TaiMed Biologics pipeline, January 2016) Updated 05 Jul 2016
01 Aug 2015 Phase Change - III Phase-III clinical trials in HIV-1 infections (Treatment-experienced) in Taiwan (IV) after August 2015 Updated 18 Jan 2016
01 Aug 2015 Phase Change - III Phase-III clinical trials in HIV-1 infections (Treatment-experienced) in Puerto Rico, USA (IV) Updated 30 Sep 2015
30 Jul 2015 Active Status Review Phase-II development is ongoing in USA and Puerto Rico Updated 30 Jul 2015
23 Jun 2015 Trial Update TaiMed Biologics plans a phase III trial for HIV-1 infections (Treatment-experienced) in USA (NCT02475629) Updated 23 Jun 2015
27 Feb 2015 Regulatory Status Ibalizumab receives breakthrough therapy designation for HIV-1 infections in USA [57] Updated 03 Mar 2015
23 Oct 2014 Regulatory Status Ibalizumab receives Orphan Drug status for HIV-1 infections in USA [56] Updated 27 Oct 2014
01 Jan 2013 Phase Change - I/II Phase-I/II clinical trials in HIV-1 infections in Taiwan (IM) Updated 30 Mar 2016
01 Jan 2013 Phase Change - I/II Phase-I/II clinical trials in HIV-1 infections in Taiwan (SC) Updated 30 Mar 2016
01 Sep 2012 Trial Update TaiMed Biologics completes a phase I trial in HIV-1 infections (In volunteers) in USA (SC) (NCT01292174 ) Updated 23 Jun 2015
30 May 2012 Trial Update TaiMed Biologics completes enrolment in its phase I trial for HIV-1 infections (in volunteers) in USA (SC) (NCT01292174) Updated 21 Jun 2012
20 Sep 2011 Scientific Update Efficacy & adverse events data from a phase IIb trial in HIV-1 infections presented at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2011) [48] Updated 11 Oct 2011
02 Jun 2011 Trial Update Investigator-sponsored phase II extension trial in HIV-1 infections completes enrolment in USA (NCT01056393) Updated 29 Aug 2012
14 Apr 2011 Trial Update TaiMed completes a phase IIb trial in HIV-1 infections in the US and Puerto Rico (NCT00784147) Updated 04 May 2011
23 Feb 2011 Licensing Status Ibalizumab is available for licensing in World as of 23 Feb 2011. http://taimedbiologics.com.tw Updated 23 Feb 2011
08 Feb 2011 Phase Change - I TaiMed initiates enrolment in a phase-I trial in HIV-1 infections (In volunteers) in USA (SC) (NCT01292174) Updated 23 Feb 2011
12 Nov 2010 Trial Update TaiMed completes enrolment in its phase IIb trial (NCT00784147) for HIV infections in the US and Puerto Rico Updated 15 Dec 2010
31 Aug 2008 Trial Update TaiMed initiates enrolment in a phase IIb trial (NCT00784147) for HIV-1 infections in the US and Puerto Rico Updated 15 Dec 2010
01 Mar 2008 Trial Update Tanox completes a phase II trial for HIV-1-infections (Treatment experinced) in USA, Canada, and Puerto Rico (NCT00089700) Updated 20 Jan 2021
26 Sep 2007 Licensing Status Genentech licences ibalizumab to TaiMed Biologics Updated 26 Nov 2007
03 Aug 2007 Company Involvement Tanox has been acquired by Genentech Updated 08 Aug 2007
16 Oct 2006 Scientific Update Late-breaking data presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2006) have been added to the Viral Infections pharmacodynamics section [58] Updated 01 Nov 2006
29 Aug 2006 Scientific Update Data presented at the XVI International AIDS Conference (AIDS-2006) have been added to the Viral Infections pharmacodynamics section [85] Updated 29 Aug 2006
12 May 2006 Scientific Update 48-Week results from a phase II clinical trial in patients with HIV infection have been added to the Viral Infections therapeutic trials section [86] Updated 12 May 2006
23 Feb 2006 Scientific Update Data presented at the 13th Conference on Retroviruses and Opportunistic Infections (CROI-2006) have been added to the Viral Infections antimicrobial activity section [87] Updated 23 Feb 2006
31 Jan 2006 Scientific Update Data presented at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2005) have been added to the adverse events, drug interactions and Viral Infections antimicrobial activity and therapeutic trials sections [88] , [89] Updated 31 Jan 2006
10 Nov 2005 Scientific Update Data from a media release have been added to the adverse events and Viral Infections therapeutic trials sections [51] Updated 10 Nov 2005
07 Nov 2005 Scientific Update Data from a media release have been added to the Viral Infections therapeutic trials section [90] Updated 07 Nov 2005
14 Mar 2005 Trial Update Tanox has completed enrolment in a phase II trial for HIV infections in the US, Canada and Puerto Rico Updated 14 Mar 2005
07 May 2004 Phase Change - II Phase-II clinical trials in HIV infections treatment in Canada (IV-infusion) Updated 14 Mar 2005
07 May 2004 Phase Change - II Phase-II clinical trials in HIV infections treatment in Puerto Rico (IV-infusion) Updated 14 Mar 2005
07 May 2004 Phase Change - II Phase-II clinical trials in HIV infections treatment in USA (IV-infusion) Updated 07 May 2004
19 Feb 2004 Scientific Update Data presented at the 11th Conference on Retroviruses and Opportunistic Infections (CROI-2004) have been added to the adverse events and Viral Infections therapeutic trials sections [91] , [92] Updated 19 Feb 2004
25 Nov 2003 Scientific Update Data from a media release have been added to the adverse events and Viral Infections therapeutic trials sections [93] Updated 25 Nov 2003
17 Nov 2003 Company Involvement IDEC Pharmaceuticals has merged with Biogen to form Biogen Idec Updated 17 Nov 2003
10 Oct 2003 Regulatory Status Ibalizumab has received fast track status for HIV infection in the US Updated 10 Oct 2003
31 Mar 2003 Scientific Update Data presented at the 10th Conference on Retroviruses and Opportunistic Infections (CROI-2003) have been added to the adverse events and Viral Infections therapeutic trials section [94] Updated 31 Mar 2003
10 Feb 2003 Trial Update A phase Ib trial in HIV infections treatment is in progress Updated 20 Mar 2003
20 Jan 2003 Trial Update Tanox has completed a phase I trial in HIV infections treatment in US Updated 20 Jan 2003
14 Jun 2002 Scientific Update A study has been added to the adverse events and Viral Infections pharmacodynamics sections [95] Updated 14 Jun 2002
15 Aug 2001 Scientific Update A preclinical study has been added to the Viral Infections antimicrobial activity and pharmacodynamics sections [96] Updated 15 Aug 2001
10 Aug 2001 Phase Change - I Phase-I clinical trials for HIV infections treatment in USA (IV-infusion) Updated 10 Aug 2001
13 Jul 2000 Phase Change - Preclinical Preclinical development for HIV infections treatment in USA (Unknown route) Updated 13 Jul 2000

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