New phase 3 data demonstrate safety, efficacy of ibalizumab

TaiMed biologics released 24-week data of a phase 3 trial that showed ibalizumab — a long-acting humanized monoclonal antibody administered intravenously every 2 weeks — was well-tolerated and safely reduced viral load in patients with multidrug resistant HIV.

The outcomes support similar findings observed in a phase 2b trial of ibalizumab.

Jacob Lalezari

“The results of the phase 3 trial of ibalizumab in [multidrug-resistant (MDR)] HIV-1 patients are particularly exciting,” Jacob Lalezari, MD, medical director for Quest Clinical Research, said in a press release. “They confirm what we had previously observed with ibalizumab, but in a patient population with higher antiretroviral drug resistance and more advanced disease.”

Lalezari and colleagues conducted a single-arm study, TMB-301, comprising 40 treatment-experienced patients with MDR HIV. They monitored patients who were on a failing drug regimen or no therapy for 7 days during a control period and then intravenously administered a 2,000-mg loading dose of ibalizumab as monotherapy. They measured antiviral activity a week later, and patients then started an optimized background regimen (OBR) that included at least one sensitive agent. After day 14, patients continued to receive ibalizumab at 800 mg every 2 weeks for 24 weeks in combination with their OBR.

Before treatment with ibalizumab, patients in the study had a mean viral load of 100,287 copies/mL and a median CD4 count of 73 cells/mm³, with nearly 30% having less than 10 CD4 cells/mm³. More than 50% of patients had resistance to all available drugs from at least three classes of ART.

After 24 weeks of treatment, patients achieved a mean reduction in HIV-1 RNA of 1.6 log₁₀, and almost half had a reduction of more than 2 log₁₀. In addition, 43% of patients had undetectable viral loads and 53% had a viral load less than 400 copies/mL. As previously reported, ibalizumab reached its primary endpoint, with 83% of patients achieving at least a 0.5 log₁₀ decrease in HIV-1 RNA by day 14 (P < .0001).

One case of immune reconstitution inflammatory syndrome, which can occur after switching to a more active ART regimen, was reported; however, there were no other serious adverse events. By the end of the treatment period, four patients died from nondrug-related causes, three withdrew from the study and two were lost to follow-up.

According to the press release, the results support a biologics license application that was submitted to the FDA. The agency granted ibalizumab with orphan drug status in 2014 and breakthrough therapy designation in 2015.

“If approved by the FDA, ibalizumab would be the first long-acting and the first biologic product to show such efficacy in patients with highly resistant HIV-1,” Lalezari said in the release.

Reference:

Lalezari J, et al. Abstract LB-6. Presented at: IDWeek; Oct. 26-30, 2016; New Orleans.

Disclosure: The study was supported by TaiMed Biologics.