A Clinical Overview of Ibalizumab

May 22, 2013

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

Adverse Events

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

Drug Interactions

Ibalizumab drug interactions are currently unknown.


  1. United States National Library of Medicine. ChemIDplus Advanced.
  2. NIAID ChemDB, HIV Drugs in Development
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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: Bethesda (MD): National Library of Medicine (US). Registered on Feb 7, 2011. NLM Identifier: NCT01292174. Last accessed March 20, 2013.

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