FDA Approves Lenacapavir for HIV Treatment

This morning the FDA announced the approval of the antiretroviral Sunlenca (lenacapavir), which is indicated for adult patients living with HIV, whose infections cannot be successfully treated with other available treatments due to resistance, intolerance, or safety considerations.

“Today’s approval ushers in a new class of antiretroviral drugs that may help patients with HIV who have run out of treatment options,” Debra Birnkrant, MD, director of the Division of Antivirals in the FDA’s Center for Drug Evaluation and Research, said in a statement.

Lenacapavir is the first of a new class of therapies called capsid inhibitors to be FDA-approved for treating HIV. This antiretroviral works by blocking the HIV-1 virus’ protein shell (the capsid), thereby interfering with multiple essential steps of the viral lifecycle.

Treatment Protocol
Lenacapavir’s starting protocol is for patients to be given as oral tablets and subcutaneous injections, followed by maintenance treatments given as single injections every six months. Lenacapavir is given in combination with other antiretroviral(s).

In today’s release, the FDA said patients should not receive lenacapavir if they also take certain drugs that cause reduced levels of lenacapavir. This may result in losing virologic response and developing viral resistance.

The Data
The approval was based around the data from the CAPELLA study, which was a double-blinded, placebo-controlled global multicenter trial designed to evaluate lenacapavir when administered every 6 months as a subcutaneous injection in heavily treatment-experienced (HTE) people with multi-drug resistant (MDR) HIV infection.

Overall, 72 participants were enrolled with 36 in each of the 2 cohorts. In terms of the makeup of the participants, 25% were female, 38% Black, the median age 52 years, 19% had VL > 100k c/mL, 64% had CD4 <200 cells/μL, 46% had HIV-1 resistant to all 4 major classes (NRTI, NNRTI, PI, INSTI), and 17% did not have any fully active agents in the optimized background regimen (OBR).

In cohort 1 (randomized group), participants were assigned (2:1) to add oral lenacapavir or placebo to their failing regimen (600 mg on Day 1[D] and 2 and 300 mg on D8). At Day 15, those on oral lenacapavir received subcutaneous (SC) lenacapavir 927 mg every 6 months; those on placebo started the 2 week oral lead-in, followed by SC Q6M. All randomized participants initiated an investigator-selected, OBR at D15 the investigators explained.

In cohort 2 (non-randomized group), the participants started OBR concurrent with lenacapavir (oral lead-in → SC). The investigators reported the secondary endpoint of W52 efficacy by FDA-snapshot algorithm in the randomized cohort and additional available efficacy and safety from both cohorts.

Earlier this year, Contagion spoke to Onyema Ogbuagu, MD, FACP, director of HIV Clinical Trials program at Yale School of Medicine, and who was the principal investigator for the CAPELLA study about it including its efficacy and safety profile as well as what the potential FDA approval of the therapy might mean for patients.

CRL
Back in March, the company’s manufacturer, Gilead, received a complete response letter (CRL) from the FDA. The letter cited Chemistry Manufacturing and Controls (CMC) issues relating to the compatibility of lenacapavir with the proposed container vial as the reason for their action.

The CRL was not reflective of the therapy itself.

“Gilead intends to provide FDA with a comprehensive plan and corresponding data to use a different vial type. We look forward to discussing this further with FDA over the coming months so that we can make this investigational new therapy available to people living with multidrug-resistant HIV as soon as possible,” Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences, said in a statement at the time.

Serving an Unmet Need
People with MDR HIV have limited or no therapy options, which can leave their disease management very challenging.

"The availability of new classes of antiretroviral medications may possibly help these patients live longer, healthier lives,” Birnkrant said.