Other Names: Hu5A8, TMB-355, TNX-355
Drug Class: Entry and Fusion Inhibitors
Registry Number: 680188-33-4 (CAS)
Chemical Name: Immunoglobulin G4, anti-(human CD4 (antigen)) (human-mouse monoclonal 5A8 γ4-chain), disulfide with human-mouse monoclonal 5A8 κ-chain, dimer
Company: TaiMed Biologics
Phase of Development: II
(Compound details obtained from ChemIDplus Advanced1 and NIAID Therapeutics Database2)
Mechanism of Action: HIV-1 entry inhibitor. Ibalizumab, a humanized monoclonal antibody (mAb), binds to extracellular domain 2 of the CD4 receptor. The ibalizumab binding epitope is located at the interface between domains 1 and 2, opposite from the binding site for major histocompatibility complex class II molecules and gp120 attachment.3,4 Ibalizumab's post-binding conformational effects prevent viral entry and fusion.5
: 3 to 3.5 days on average (estimated from a multiple-dose study of weekly ibalizumab10 mg/kg in one study arm and biweekly ibalizumab 25 mg/kg in another study arm, given via intravenous [IV] infusion in HIV-infected adults).4
Resistance: Reduced ibalizumab susceptibility is associated with mutations that disrupt potential N-linked glycosolation sites (PNGS) in variable region 5 (V5) of HIV-1 envelope glycoproteins.3,6 A Phase Ib study indicated that cross-resistance between enfuvirtide and ibalizumab does not occur.5
Ibalizumab can be administered via IV infusion.
Phase IIa (treatment-experienced):
- Ibalizumab 10 mg/kg weekly for 8 weeks (followed by 10 mg/kg biweekly) or 15 mg/kg biweekly versus placebo, each in combination with an optimized background regimen.7
Phase IIb (treatment-experienced):
- Ibalizumab 800 mg every 2 weeks or 2000 mg every 4 weeks, each in combination with an optimized background regimen.8
Ibalizumab can also be administered via subcutaneous (SC) injection.
Phase I (healthy volunteers):
- Ibalizumab 120 mg, 240 mg, or 480 mg weekly versus placebo.9
The most common treatment-emergent adverse events occurring in a Phase IIb trial were rash, diarrhea, headache, and nausea. Most events were mild to moderate. No drug-related deaths, serious adverse events, or discontinuations occurred. Laboratory and vital sign abnormalities were determined not to be clinically relevant.8
Ibalizumab drug interactions are currently unknown.
- United States National Library of Medicine. ChemIDplus Advanced.
- NIAID ChemDB, HIV Drugs in Development
- Toma J, Weinheimer SP, Stawiski E, et al. Loss of asparagine-linked glycosylation sites in variable region 5 of human immunodeficiency virus type 1 envelope is associated with resistance to CD4 antibody ibalizumab. J Virol. 2011 Apr;85(8):3872-80.
- Jacobson JM, Kuritzkes DR, Godofsky E, et al. Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1-infected adults. Antimicrob Agents Chemother. 2009 Feb;53(2):450-7.
- Bruno CJ, Jacobson JM. Ibalizumab: an anti-CD4 monoclonal antibody for the treatment of HIV-1 infection. J Antimicrob Chemother. 2010 Sep;65(9):1839-41.
- Toma J, Weinheimer SP, Stawiski E, et al. Loss of Asparagine-Linked Glycosylation Sites in Variable Region Five of Human Immunodeficiency Virus Type 1 Envelope is Associated with Resistance to CD4 Antibody Ibalizumab. Poster presented at: 18th Conference on Retroviruses and Opportunistic Infections (CROI); February 27-March 2, 2011; Boston, MA. Poster 586.
- Norris D, Morales J, Gathe J, et al. Phase 2 efficacy and safety of the novel entry inhibitor, TNX-355, in combination with optimized background regimen (OBR). Abstract presented at: 16th International AIDS Conference; August 13-18, 2006; Toronto, Canada. Abstract TUPE0058.
- Khanlou H, Gathe J Jr, Schrader S, Towner W, Weinheimer S, Lewis S. Safety, Efficacy, and Pharmacokinetics of Ibalizumab in Treatment-Experienced HIV-1 Infected Patients: a Phase 2b Study. Abstract presented at: 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17-20, 2011; Chicago, IL; Abstract H2-794b.
- TaiMed Biologics Inc. A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Sequential Dose-Escalation Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered Ibalizumab in HIV-Negative, At-Risk Volunteers. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on Feb 7, 2011. NLM Identifier: NCT01292174. Last accessed March 20, 2013.