By Ed Susman
An investigational long-acting injectable, lenacapavir, helped control HIV infection even in patients who had developed resistance to multiple classes of drugs, researchers reported at the Virtual Conference on Retroviruses and Opportunistic Infections .
Aproximadamente el 88% de los pacientes a los que se agregó lenacapavir a sus regímenes fallidos actuales pudieron lograr al menos una reducción de 0,5 log 10 en la carga viral del VIH dentro de los 15 días posteriores al inicio del tratamiento, el criterio de valoración principal del ensayo, en comparación con el 17% de los pacientes que recibieron placebo con sus regímenes actuales ( P <0,0001), informó Sorana Segal-Maurer, MD, de NewYork-Presbyterian Queens en Flushing, Nueva York.
In fact, the average reduction achieved by the 24 patients who received subcutaneous injections of lenacapavir was 1.93 log 10 compared to 0.29 log 10 for the 12 patients on placebo, Segal-Maurer reported in her oral presentation.
To date, he said, 72% of patients who had been receiving the failed regimens had achieved viral loads below the detection limit of 50 copies/ mm3 .
The mean increase in CD4 positive counts was 73 cells/ mm3 after 26 weeks.
Segal-Maurer said that among the 72 patients who received lenacapavir, two developed resistance to the capsid inhibitor, but the M66.1-resistant strain that emerged disrupts viral replication.
All patients reported adverse events during the trial, most commonly headache, nausea, cough, diarrhea, and rash, but none led to discontinuation of the study. 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 persisted for up to 4 months, he said. All nodules were considered Grade 1, and no participants discontinued treatment due to injection site reactions.
“Lenacapavir is a potent, long-acting, first-in-class HIV capsid inhibitor and represents a novel mechanism of action for the 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 treatment-experienced people living with multidrug-resistant HIV," he added. "These data support the ongoing evaluation of lenacapavir for the 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 describing the findings, told MedPage Today . “Lenacapavir is an incredibly potent molecule. I think this new generation of long-acting molecules that can be delivered sustainably is going to revolutionize prevention and treatment.”
“I was quite surprised that people whose medications were failing could receive this subcutaneous injection and did incredibly well,” Hillier continued. “I think it will lead us to a future where we’ll have truly new options for managing treatments with these patients who have limited choices.”
For the study, Segal-Maurer and colleagues enrolled HIV-diagnosed patients whose viral loads were detectable at a level above 400 copies/ mm3 . An analysis of the virus also had to show resistance to at least two antiretroviral agents from three of the four major classes of antiretrovirals, and the regimens had to contain no more than two less active agents.
Participants received oral lenacapavir for 14 days before receiving subcutaneous lenacapavir every 6 months for 52 weeks. The lenacapavir was administered in addition to the best available optimized antiretroviral regimen. After the trial was completed, the patients who received placebo and an additional 36 patients received open-label lenacapavir, for a total of 72 people in the program, Segal-Maurer explained.
The median age of the participants was 52 years, and the non-randomized patients were generally younger than those in the blinded trial.
Approximately 25% of the participants were female at birth. Approximately 38% identified as Black, and approximately 21% were Latino or Hispanic. Approximately 90% of the participants had been exposed to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors.
Main source
Conference on Retroviruses and Opportunistic Infections
Reference source: Segal-Maurer S, et al "Potent antiviral activity of lenacapavir in phase 2/3 in PWH with extensive experience in ART" CROI 2021; Abstract 127.