People with multidrug-resistant (MDR) HIV have limited or no therapy options, which can leave their disease management very challenging. The antiviral, lenacapavir (Sunlenca 463.5 mg/1.5 mL injection), was FDA approved late last year for this patient population, and was indicated specifically 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 at that time. "The availability of new classes of antiretroviral medications may possibly help these patients live longer, healthier lives,” Birnkrant said at the time.
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 MDR HIV.
Yesterday, Gilead announced new CAPELLA data at the ongoing European AIDS Conference (EACS) supporting its HIV antiviral. The latest results include two-year data from the Phase 2/3 CAPELLA trial, including updated resistance data on lenacapavir.
What You Need to Know
Lenacapavir (Sunlenca 463.5 mg/1.5 mL injection) received FDA approval last year for the treatment of adult patients with multidrug-resistant (MDR) HIV.
The approval of lenacapavir was based on data from the CAPELLA study, a double-blinded, placebo-controlled global multicenter trial. The study involved heavily treatment-experienced (HTE) people with MDR HIV.
The new data suggests that lenacapavir has the potential to improve clinical outcomes for adults with HIV who are heavily treatment experienced. It may also positively impact their health-related quality of life.
CAPELLA investigators enrolled 72 participants with advanced HIV disease. Of the 27 participants who met the resistance analysis criteria, 13 did not develop resistance to lenacapavir. Fourteen participants developed lenacapavir resistance-associated mutations; importantly, all 14 either had inadequate adherence to their OBR (n=10) or an OBR lacking fully active antiretrovirals (n=4), 7 of the 14 participants with Sunlenca resistance resuppressed (HIV-1 <50 copies/mL) upon re-adherence to their OBR or with OBR change.
“The new findings presented at EACS 2023 demonstrate that Sunlenca has the potential to improve clinical outcomes for adults with HIV who are heavily treatment experienced and also positively impact their health-related quality of life,” Jared Baeten, MD, PhD, vice president, HIV Clinical Development, Gilead Sciences, said in a statement. “These unmet needs fueled our research teams at Gilead to develop Sunlenca, an innovative treatment option that helps respond to the unmet needs of adults with limited therapy choices.”
Gilead discussed findings last year at the time of the approval. Seventy-two 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.
Last 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. In the interview, Ogbuagu discussed the therapy's efficacy and safety profile.
New Data Presented at EACS 2023 Further Demonstrate Strong Clinical Profile of Twice-Yearly Sunlenca® for Adults With Multi-Drug Resistant HIV. Businesswire press release. October 20, 2023. Accessed October 20, 2023.