Positive results have been reported from a pivotal phase 3 study of ibalizumab, a humanized monoclonal antibody, in patients with multidrug-resistant human immunodeficiency virus-1 (HIV-1) infection.
Unlike other antiretroviral agents, ibalizumab binds primarily to the second extracellular domain of the CD4 receptor, away from binding sites on major histocompatibility complex II (MHC II) molecules. It potentially prevents HIV from infecting CD4-positive immune cells while preserving normal immunologic function. Ibalizumab is active against HIV-1 that is resistant to all approved antiretroviral agents, according to its developer (Theratechnologies Inc.).
The TMB-301 trial was a single-arm, 24-week study of ibalizumab plus an optimized background regimen in treatment-experienced patients infected with multidrug-resistant HIV-1. The study’s primary objective was to demonstrate the antiviral activity of ibalizumab seven days after the first dose. Patients receiving their current failing antiretroviral therapy (ART), or no therapy, were monitored during a seven-day control period. Thereafter, a loading dose of 2,000 mg of intravenous (IV) ibalizumab was the only ART added to their regimen. Ibalizumab was continued at a dosage of 800 mg IV every two weeks through 24 weeks of treatment. A total of 40 patients were enrolled in the study.
Patients with multidrug-resistant HIV-1 infection experienced a significant reduction in their viral loads after receiving a loading dose of ibalizumab 2,000 mg IV in addition to their failing ART or no therapy. Seven days after the loading dose, 83% of patients achieved a 0.5 log10 decrease from baseline compared with a 3% decrease during the seven-day control period. These results were statistically significant (P < 0.0001).
During the same period, 60% of patients achieved a decrease of 1.0 log10 in the viral load (P < 0.0001). The average reduction for the total population was 1.1 log10 (P < 0.0001). No treatment-related serious adverse events or discontinuations were reported during the initial seven-day treatment period.
Ibalizumab has received breakthrough therapy status from the FDA. This designation is awarded if a drug may provide a substantial improvement over what is currently available to address a serious and life-threatening condition. Ibalizumab has also received an orphan drug designation.
Source: Theratechnologies; October 28, 2016.