A 24-week phase 3 study has confirmed the safety and efficacy results with ibalizumab (Theratechnologies Inc./TaiMed Biologics) observed in a previously completed phase 2b trial, despite the fact that the patient population in the phase 3 investigation had higher levels of multidrug-resistant human immunodeficiency virus-1 ( HIV-1) and more-advanced disease at the time of enrollment. Ibalizumab is a humanized monoclonal antibody.
At baseline, the subjects had a mean HIV-1 viral load of 100,287 copies/mL. The median CD4 count was 73 cells/mm3, and nearly 30% of participants had less than 10 CD4 cells/mm3. More than 85% of the subjects had more than one identified mutation conferring resistance to nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), or protease inhibitors, and more than 60% of the subjects showed resistance to at least one integrase inhibitor. The subjects were infected with HIV-1 that was resistant to more than 75% of all drugs in the NRTI, NNRTI, protease inhibitor classes, and to one or two drugs in the integrase inhibitor class, on average. Just over 50% of the subjects had HIV-1 that resisted all available drugs from at least three classes of antiretroviral therapy.
After 24 weeks of treatment with ibalizumab, the mean reduction in the viral load was 1.6 log10, and 48% of the subjects showed a viral load reduction of more than 2.0 log10. At the end of the treatment period, using ibalizumab with an optimized background regimen, the proportion of participants with an undetectable HIV-1 load (less than 50 copies/mL) was 43%, representing a mean viral load reduction of 3.1 log10, and 53% of the subjects had a mean viral load of less than 400 copies/mL.
The results also indicated that 33 of the 40 subjects (83%) met the primary endpoint of a reduction of at least 0.5 log10 in the viral load after seven days of treatment with ibalizumab.
Unlike other antiretroviral agents, ibalizumab binds primarily to the second extracellular domain of the CD4 receptor, away from binding sites on the major histocompatibility complex II (MHC II) molecule. The drug 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.
Source: Theratechnologies; November 10, 2016.