Research of broadly neutralizing antibodies — which are able to neutralize multiple strains of HIV — have the potential to treat, prevent and maybe even cure HIV.
A proof-of-concept study has clinicians who treat patients with HIV excited about new possibilities for treatment and possibly remission of HIV. They addressed an audience at ID Week in Boston in a session today about what’s hot in HIV research.
Michelle Cespedes, M.D., professor of medicine, Icahn School of Medicine at Mount Sinai in New York and Bernard Macatangay, M.D., associate professor of medicine and immunology at the University of Pittsburgh, discussed a newer approach in HIV research that has achieved some early success.
Results of a phase 1b study released earlier this year evaluated Sunlenca (lenacapavir) in combination with broadly neutralizing antibodies. These antibodies target specific epitopes of the virus and offer a new way to kill HIV-1 cells. They also have the ability to neutralize multiple strains of HIV, giving researchers hope for therapies that can protect against HIV that has mutated.
Macatangay said it could be possible to cure HIV, and he highlighted several cases in the literature where stem cell transplantation resulted in HIV remission, and patients were able to stop antiretroviral therapy. The use of broadly neutralizing antibodies to enhance the immune response is one strategy investigators with an eye toward achieving HIV remission.
Cespedes reviewed data from the CAPELLA trial, which led to the FDA approval of Gilead Sciences’ Sunlenca in December 2022 to treat HIV-1 infection in heavily treated adults with multidrug resistant (MDR) HIV-1 infection.
Sunlenca is the first of a new class of drugs called capsid inhibitors. Sunlenca works by blocking the HIV-1 virus’ protein shell (the capsid) and disrupts the HIV viral life cycle at several points. The twice-yearly treatment is for patients whose HIV is not adequately controlled. About 2% of adults living with HIV are unable to maintain virus suppression due to resistance, intolerance or safety.
Sunlenca is currently being studied in trials for patients who haven't been treated, for preexposure prophylaxis (PrEP) and in patients who have treated with other HIV drugs (switching studies).
But more exciting is a study that looked at the combination of Sunlenca with the broadly neutralizing antibodies teropavimab and zinlirvimab as a potential long-acting treatment regimen. The combination of Sunlenca with the two broadly neutralizing antibodies has the potential to keep HIV at undetectable levels and drive remission.
Earlier this year, Gilead released results of a phase 1b study that showed that the Sunlenca-teropavimab-zinlirvimab combination was well tolerated with high efficacy in patients whose viral load had been previously suppressed with standard antiretroviral therapy. At week 26, 18 of the 20 patients enrolled maintained viral suppression. There were no serious adverse events that led to study discontinuation.
Gilead is currently recruiting for a phase 2 study that will assess two different dose levels of the broadly neutralizing antibodies and will evaluate the efficacy of switching to a regimen of Sunlenca, teropavimab, and zinlirvimab compared with continuing on oral antiretroviral therapy. The study will enroll 75 patients.
Separately at the ID Week meeting, Onyema Ogbuagu, MBBCh, associate professor of Medicine and director of antivirals and vaccines research program at the Yale School of Medicine, presented a poster that assessed long-term results of Sunlenca alone. Researchers assessed heavily treated patients who were enrolled in the ongoing CAPELLA phase 2/3 study and who continued in the trial after week 52.
They found that at week 104 for the 66 patients who continued treatment, Sunlenca along with antiretroviral therapy continued to result in high and sustained levels of viral suppression. No patients experienced a serious adverse event, and one patient discontinued the study because of an injection site reaction.