Efficacy, safety, and pharmacokinetics of lenacapavir oral bridging when subcutaneous lenacapavir cannot be administered

作者：Onyema Ogbuagu, Anchalee Avihingsanon, Sorana Segal-Maurer, Hui Wang, Vamshi Jogiraju, Renu Singh, Martin S. Rhee, Hadas Dvory‐Sobol, Peter Sklar, Jean‐Michel Molina · 发表于：AIDS · 年份：2025 · DOI：10.1097/qad.0000000000004142 · 被引用次数：8 · 研究领域：HIV/AIDS drug development and treatment、HIV Research and Treatment、Virus-based gene therapy research

OBJECTIVE: To assess efficacy, safety and pharmacokinetics (PK) of oral lenacapavir (LEN) when used as oral bridging (OB) between delayed subcutaneous (SC) LEN injections. DESIGN: Post-hoc analysis of participants in two clinical trials of SC LEN for HIV-1 treatment who required OB when LEN SC dosing was interrupted. METHODS: Oral LEN [300 mg once weekly (QW)] was initiated within 2 weeks of the next scheduled injection (dosing interval: 26 weeks). Efficacy, safety, and PK were assessed every 10-12 weeks. RESULTS: Overall, 139 participants received ≥1 dose of oral 300 mg QW LEN plus other antiretrovirals. Median duration of OB was 19 weeks in both clinical trials. By missing = excluded analysis, over 95% of participants maintained virologic suppression (HIV-1 RNA <50 copies/mL) at Weeks 10, 20, and 30. Treatment-emergent AEs (TEAEs) were similar to those with SC LEN (excluding injection site reactions). No Grade ≥3 or serious TEAEs were considered related to oral LEN. Throughout OB, mean LEN plasma concentrations and lower bound of 90% confidence intervals (CIs) were consistently above inhibitory quotient 4 (4-fold in-vitro protein binding-adjusted 95% effective concentration). OB adherence (by pill count) was ≥95% in the majority of participants in both clinical trials. CONCLUSIONS: High rates of virological suppression were maintained during OB. Oral 300 mg QW LEN was well tolerated and provided adequate plasma concentrations to bridge SC LEN dosing. This analysis supports ...