Phase 3 data for ibalizumab showed that nearly half of patients had a reduction in viral load of more than 80% after 25 weeks of therapy.
Brinda Emu, MD
A newly published phase 3 study of patients with multidrug-resistant (MDR) HIV shows that ibalizumab can be a safe and effective option for patients with limited other avenues of treatment.
The study was the culmination of years of research into a drug designated a breakthrough therapy and fast-tracked by the US Food and Drug Administration (FDA). The FDA approved ibalizumab for the treatment of patients with MDR HIV in March 2018. The drug is being marketed by TaiMed Biologics under the brand name Trogarzo.
Corresponding author Brinda Emu, MD, an assistant professor of medicine at Yale University, said the vast majority of patients with HIV find success taking existing antiretroviral therapies (ARTs), if they take the drugs consistently. The success of ART is broad, she said, thanks to the fact that the current ART drugs have varying mechanisms of action, high barriers to resistance, relatively few side effects, and a low pill burden.
“Due to these advances, the number of patients with multidrug-resistant virus is small,” she said. “However, this small group of individuals with MDR HIV is at high risk for virologic and immunologic failure, putting them at risk for development of serious AIDS related illnesses and death.”
Emu said there can be several reasons why a patient could harbor multidrug-resistant HIV, but she said the main reason is sequential use of drug regimens that have been unable to control viremia, possibly due to poor potency, low patient adherence, or other issues.
The phase 3 study included 40 patients with multidrug-resistant HIV-1, each of whom had viral loads exceeding 1000 copies of HIV-1 RNA per milliliter (c/mL). Patients in the study spent the first week on their existing therapies, then received a loading dose of 2000 mg of ibalizumab, followed by 800-mg doses of ibalizumab every 2 weeks through week 25 of the study.
The primary endpoint of the study was the proportion of patients who achieved a reduction in viral load of at least 0.5 log 10 c/mL. At 25 weeks, patients who had taken ibalizumab in combination with a background regimen had an average decrease of 1.6 log 10 c/mL from their baseline load, and 43% of patients had a viral load of less than 50 c/mL. Fully half (50%) of patients had a viral load of less than 200 c/mL.
Emu said ibalizumab is a monoclonal antibody that works by binding to the CD4 receptors on host cells, thus preventing viral entry.
“The key to targeting drug-resistant virus is finding new mechanisms of action with non-overlapping resistance and evidence of potent antiviral activity,” she said. “Ibalizumab fits that definition, thus making it an attractive option for patients who have limited alternative options.”
Ibalizumab is a good choice for a very specific group of patients, she said, but added that physicians should weigh each patient’s specific risks and needs carefully. One issue that differentiates ibalizumab from other ARTs is that it’s administered intravenously, rather than as a pill.
“Providers should engage in dialogue with patients about their interest and ability with complying with the regimen,” she said. “Potential logistical hurdles of biweekly IV administration must be weighed against the potential benefits of frequent visits, including the ability to quickly ascertain side effects to all medications, reminders about adherence, and building strong provider-patient relationships.”
The study, “Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1,” was published in the New England Journal of Medicine.