The Food and Drug Administration (FDA) has approved Sunlenca® (lenacapavir), in combination with other antiretroviral(s), for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant (MDR) HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.
Lenacapavir is a first-in-class, long-acting HIV-1 capsid inhibitor designed to inhibit HIV replication by interfering with capsid-mediated uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation. The approval was based on data from the CAPELLA trial (ClinicalTrials.gov Identifier: NCT04150068), which evaluated the efficacy and safety of lenacapavir in heavily treatment-experienced patients with MDR HIV-1 infection who had previously received a median of 9 antiretroviral drugs.
The trial was composed of 2 cohorts: a randomized cohort with participants who had a less than 0.5 log10 HIV-1 RNA decline compared with the screening visit (cohort 1), and a nonrandomized cohort with participants who had a 0.5 or greater log10 HIV-1 RNA decline compared with the screening visit or after cohort 1 reached its planned sample size (cohort 2).
In cohort 1 (n=36), patients were randomly assigned 2:1 to receive oral lenacapavir (n=24) or placebo (n=12) for 14 days, in addition to continuing their failing regimen (functional monotherapy period). On day 15 after enrollment, lenacapavir was administered subcutaneously at a dose of 927mg every 6 months. After the functional monotherapy period, patients in the placebo arm received oral lenacapavir followed by subcutaneous doses every 6 months. Both groups continued receiving an optimized background regimen.
At the end of the initial 14 days, 87.5% of patients treated with lenacapavir met the primary endpoint (achieving a viral load reduction of ≥0.5 log10 copies/mL from baseline in HIV-1 RNA) compared with 16.7% of those treated with placebo (treatment difference, 70.8%; [95% CI, 34.9-90.0]; P <.0001). At 26 weeks, 81% of patients treated with lenacapavir achieved HIV RNA suppression (HIV-1 RNA <50 copies/mL). After 52 weeks, 83% of lenacapavir-treated patients continued to have HIV RNA suppression. At week 26 and week 52, the mean change from baseline in CD4+ cell count was 81 cells/mm3 (range, -101 to 522) and 82 cells/mm3 (range, -194 to 467), respectively.
In cohort 2 (n=36), all patients received lencapavir and optimized background therapy starting on day 1. At week 26 and week 52, 81% and 72% of patients achieved HIV1 RNA <50 copies/mL, respectively, and the mean change from baseline in CD4+ cell count was 97 cells/mm3 (range, -103 to 459) and 113 cells/mm3 (range, -124 to 405), respectively.
The most common adverse reactions reported with lenacapavir were injection site reactions and nausea.
“Following today’s decision from the FDA, lenacapavir helps to fill a critical unmet need for people with complex prior treatment histories and offers physicians a long-awaited twice-yearly option for these patients who otherwise have limited therapy choices,” said Sorana Segal-Maurer, MD, Director of the Dr James J. Rahal Jr. Division of Infectious Diseases at NewYork-Presbyterian Queens, Professor of Clinical Medicine at Weill Cornell Medicine and the Site Principal Investigator for the CAPELLA trial.
Sunlenca is supplied as 300mg tablets and as a 463.5mg/1.5mL injection. The product is expected to be available in January 2023.
- Sunlenca® (lenacapavir) receives FDA approval as a first-in-class, twice-yearly treatment option for people living with multi-drug resistant HIV. News release. Gilead Sciences, Inc. Accessed December 22, 2022. https://www.businesswire.com/news/home/20221221005541/en/Sunlenca%C2%AE-lenacapavir-Receives-FDA-Approval-as-a-First-in-Class-Twice-Yearly-Treatment-Option-for-People-Living-With-Multi-Drug-Resistant-HIV.
- FDA approves new HIV drug for adults with limited treatment options. News release. US Food and Drug Administration. Accessed December 22, 2022. https://www.prnewswire.com/news-releases/fda-approves-new-hiv-drug-for-adults-with-limited-treatment-options-301709176.html.