An investigational long-acting injectable, lenacapavir, helped control HIV infection even in patients who had developed resistance to multiple drug classes, researchers reported at the .
About 88% of patients who had lenacapavir added to their current failing regimens were able to achieve at least a 0.5 log10 reduction in HIV viral load within 15 days of beginning treatment -- the trial's primary endpoint -- compared with 17% of patients who received placebo with their current regimens (P<0.0001), reported Sorana Segal-Maurer, MD, of NewYork-Presbyterian Queens in Flushing, New York.
In fact, the mean reduction achieved by the 24 patients who received subcutaneous injections of lenacapavir was 1.93 log10 compared with 0.29 log10 for the 12 patients on placebo, Segal-Maurer reported in her oral presentation.
To date, she said, 72% of patients who had been receiving the failing regimens had achieved viral loads below the 50-copies/mm3 detection limit.
The mean increase in CD4-positive counts was 73 cell/mm3 after 26 weeks.
Segal-Maurer said that among the 72 patients on lenacapavir, two developed resistance to the capsid inhibitor, but the M66.1-resistant strain that emerged impairs virus replication.
All the patients reported adverse events during the trial -- most frequently headache, nausea, cough, diarrhea, and rash, but none led to study discontinuation. One patient who developed pneumonia in the study died. Segal-Maurer said the team did not believe the pneumonia was related to the study drug.
Injection site reactions generally resolved after a few days, but nodules that occurred in 18% of patients stayed around for as long as 4 months, she said. All the nodules were considered to be Grade 1, and no participant discontinued due to injection site reactions.
"Lenacapavir is a potent, long-acting, first-in-class HIV capsid inhibitor and represents a new mechanism of action for treatment of HIV infection," Segal-Maurer said. "The study is ongoing, and longer-term data will be presented as follow-up continues."
"Lenacapavir has the potential to become an important agent for highly treatment experienced people living with HIV with multiple drug-resistant virus," she added. "These data support the ongoing evaluation of lenacapavir for treatment and prevention of HIV."
"I was blown away by these results," Sharon Hillier, PhD, of the University of Pittsburgh School of Medicine, who moderated a press conference where the results were described, told 鶹ý. "Lenacapavir is such an amazing potent molecule. This new generation of long-acting molecules that could be given in a sustained delivery way, I think are going to revolutionize prevention and treatment."
"I was quite taken that people whose medications were failing could take this injection subcutaneously and did amazingly well," Hillier continued. "I think it will lead us to a future where we are going to have really new options for how to manage treatments with these patients who have limited options."
For the study, Segal-Maurer and colleagues enrolled patients diagnosed with HIV whose viral loads were detectable at a level greater than 400 copies/mm3. An analysis of the virus also had to show resistance to at least two antiretroviral agents from three of four main classes of antiretrovirals, and that the regimens contained no more than two less fully active agents.
Participants received oral lenacapavir for 14 days before receiving subcutaneous lenacapavir ever 6 months for 52 weeks. The lenacapavir was administered on top of the optimized best regimen of available antiretrovirals. After the trial was completed, patients on placebo and another 36 patients were given open-label lenacapavir, for a total of 72 individuals in the program, Segal-Maurer explained.
The median age of the participants was 52, with the non-randomized patients generally younger than those in the blinded trial.
About 25% of the participants were female at birth. About 38% identified as Black, and about 21% were Latino or Hispanic. About 90% of the participants had been exposed to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors.
Disclosures
The trial was sponsored by Gilead Sciences.
Segal-Maurer disclosed relationships with Gilead, Janssen Therapeutics, ViiV Healthcare, U.S. HealthConnect, and Bastian.
Hillier has disclosed relationships with Becton, Dickinson and Company, Cepheid, Curatek, Dare Biosciences, Hologic, Merck, and Pfizer.
Primary Source
Conference of Retroviruses and Opportunistic Infections
Segal-Maurer S, et al "Potent Antiviral Activity of Lenacapavir in Phase 2/3 in Heavily ART-Experienced PWH" CROI 2021; Abstract 127.