The FDA has approved lenacapavir (Sunlenca) in combination with antiretroviral therapy (ART) for HIV-1 patients who have received a lot of prior treatment and have infections that are resistant to other existing medications or who cannot tolerate those medications.

Initially delivered as oral tablets (300 mg) and subcutaneous injections (463.5 mg/1.5 mL), lenacapavir is a first-in-class long-acting HIV capsid inhibitor. Maintenance injections are after that given every six months.

The approval was based on a multicenter CAPELLA trial, which included 72 patients with HIV-1 infections that were drug-resistant. Despite being on ART regimens, the patients in the phase II/III study showed significant viral levels.

During a randomized, double-blind phase of the experiment 36 patients were given oral lenacapavir or a placebo along with their failed regimens. At 14 days, 87.5% of lenacapavir patients had reduced their HIV-1 viral load by 0.5 log10 compared to 16.7% of placebo patients. At 26 and 52 weeks into an open-label phase, 81% and 83% of patients on lenacapavir had undetectable levels of HIV RNA.

Lenacapavir use was associated with common side effects, including nausea and injection site reactions, some of which were described as nodules or indurations that lasted for some individuals. Furthermore, the FDA warned that immune reconstitution syndrome could also be developed and that low levels of lenacapavir from missed doses might increase the risk of viral resistance.

The risk of drug interactions could persist as residual amount of the drug linger in the body for up to a year. According to Gilead, CYP3A inducers can lower lenacapavir concentrations whereas CYP3A, P-gp, and UGT1A1 inhibitors can raise levels of the capsid inhibitor.

Experts from the trial said that approval of lenacapavir by the FDA will help to meet the needs of patients with complicated previous treatment histories and give doctors a long-needed twice-yearly treatment alternative for these patients who would otherwise have few treatment options.

(Source: https://www.medpagetoday.com/hivaids/hivaids/102382)