Ibalizumab Demonstrates Promising Results in Phase 3 Trial for Multidrug Resistant HIV

New data from a pivotal phase 3 trial of long-acting antiretroviral ibalizumab show additional secondary safety and efficacy endpoint results that further support Theratechnologies upcoming FDA submission, according to a press release.

Ibalizumab is an investigational humanized monoclonal antibody for the treatment of multidrug resistant (MDR) HIV-1 infection. The drug is designed to bind primarily to the second extracellular domain of the CD4+ T cell receptor.

The FDA has granted Breakthrough Therapy and Orphan Drug designation for ibalizumab.

The 24-week, single arm, phase 3 TMB-301 study examined ibalizumab plus optimized background regimen (OBR) in 40 treatment-experienced patients with MDR HIV-1, according to the release. The primary objective was to demonstrate the antiviral activity of ibalizumab 7 days after the first dose of ibalizumab.

The primary efficacy endpoint was the proportion of patients achieving a ≥ 0.5 log₁₀ decrease in HIV-1 RNA 7 days after initiating ibalizumab therapy, day 14 of the study. Ibalizumab was continued at doses of 800 mg IV every 2 weeks through 24 weeks on treatment.

The results of the study showed that patients with MDR HIV-1 infection experienced a mean increase in CD4+ T cell of 48 cells/µL after 24 weeks of treatment with ibalizumab plus an OBR, according to the release.

Prior data show 83% of patients achieved a ≥ 0.5 log₁₀ decrease in viral load from baseline 7 days after a single loading dose of 2000 mg of ibalizumab, and a mean decrease in viral load of 1.6 log₁₀ over the 24 week treatment, with more than 48% of patients who experienced a reduction of more than 2.0 log₁₀ in their viral load.

“CD4+ T cells play an important role in protecting the body from infection," said Dr. Brinda Emu, Assistant Professor of Medicine, Infectious Diseases, Yale School of Medicine, New Haven, CT. “The higher the CD4+ T cell count, the better able you are to fight HIV and other infections. This meaningful increase in CD4+ T cell counts is particularly important for patients with multidrug resistant virus, as they often have the most advanced disease. These data suggest that for these patients, ibalizumab could be an important new treatment option.”

The results of the TMB-301 study showed that patients who received a single loading dose of 2000-mg ibalizumab intravenously, in addition to failing ART or no therapy, experienced a significant decrease in viral load, and were maintained during the 24-week trial.

At the end of the treatment period, the proportion of study participants with undetectable viral load (HIV-1 <50 copies/mL) was 43% (mean viral load reduction of 3.1 log₁₀), and 50% of patients had a viral load lower than 200 copies/mL, the press release stated.

No serious adverse events (AEs) were reported in the study, excluding 1 case of immune reconstitution inflammatory syndrome. A majority of treatment-induced AEs were mild to moderate in severity.

“There is an urgent need for a drug with a new mechanism of action for patients infected with multidrug resistant HIV-1,” said Christian Marsolais, PhD, senior vice president and chief medical officer of Theratechnologies Inc. “These results continue to support the submission of a Biologics License Application (BLA) to the FDA, and if approved by the FDA, ibalizumab will be the first antiretroviral treatment with a new mechanism of action to be approved in close to 10 years.”

The findings were presented at a late-breaker session at the Conference on Retroviruses and Opportunistic Infections (2017).