CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

change from baseline in plasma HIV-1 RNA was −1.17, −2.15, and −2.31 log10 c/mL for VH-184 at 10, 50, and 300 mg, respectively. An exposure-response relationship was observed for plasma HIV-1 RNA decrease. During monotherapy, the only adverse event (AE) reported in >1 participant was vomiting (VH-184, n=2 [11%]). Each drug-related AE was reported in 1 participant. All AEs were grade 1 or 2 in severity. No AEs leading to withdrawal, serious AEs, or deaths were reported during monotherapy or follow-up. There were no clinically relevant changes in clinical laboratory parameters, electrocardiograms, or vital signs. No VH-184 genotypic or phenotypic resistance was detected at Day 10, the end of monotherapy. Conclusions: VH-184 monotherapy demonstrated rapid and highly potent antiviral activity, with HIV-1 RNA declines of >2 log 10 c/mL at the highest doses, and was well tolerated, with a favorable safety and tolerability profile. An exposure-response relationship was established comparable to the maximum effect with other INSTIs. These results support further development of VH-184 as the core agent in a complete long-acting regimen for the treatment of HIV-1. Proof-of-Concept Trial of Oral VH4011499 (VH-499), a New HIV-1 Capsid Inhibitor Rulan Griesel 1 , Sebastián A. Núñez 2 , Alma Minerva Pérez Rios 3 , Clara Lehmann 4 , Carmen Busca 5 , Pedro Cahn 6 , Amy Pierce 7 , Jerry L. Jeffrey 7 , Nilay Thakkar 8 , Bronagh Shepherd 9 , Veronica Bainbridge 9 , Konstantinos Angelis 9 , Carlye McMillan 10 , Cynthia McCoig 11 , Paul Benn 1 1 ViiV Healthcare, Brentford, UK, 2 Centro Médico Maffei and Investigación Clínica Aplicada, Buenos Aires, Argentina, 3 Centro de Investigación Farmacéutica Especializada, Guadalajara, Mexico, 4 University Hospital Cologne, Cologne, Germany, 5 Hospital La Paz Institute for Health Research, Madrid, Spain, 6 Fundación Huésped, Buenos Aires, Argentina, 7 ViiV Healthcare, Durham, NC, USA, 8 GSK, Collegeville, PA, USA, 9 GSK, London, UK, 10 GSK, Mississauga, ON, Canada, 11 ViiV Healthcare, Madrid, Spain Background: New long-acting antiretroviral therapy (ART) regimens are needed to expand treatment choices for people living with HIV-1. VH4011499 (VH-499) is a new HIV-1 capsid inhibitor in development as a long-acting antiretroviral agent for the treatment and prevention of HIV-1. Here, we present antiviral effect, pharmacokinetics, safety, and tolerability data for VH-499 from a proof-of concept, phase 2a trial in people living with HIV-1. Methods: This randomized, double-blind, placebo-controlled trial evaluated oral VH-499 monotherapy in adults naive to ART with HIV-1 RNA ≥3000 c/mL. In the 10-day monotherapy period, participants received oral VH-499 25, 100, or 250 mg or placebo on Day 1 (baseline) and Day 6. After the monotherapy period, participants initiated locally sourced, standard-of-care ART. The primary endpoint was maximum change from baseline in plasma HIV-1 RNA through Day 11. Secondary endpoints included pharmacokinetics, exposure-response relationships, safety, and tolerability. Results: A total of 23 participants were enrolled (VH-499, n=20; placebo, n=3), 83% were assigned male at birth, 65% identified as White, and 65% identified as Hispanic or Latin American; median (range) age was 31 (18-62) years. Plasma

HIV-1 RNA (−2.2 [0.43] log 10 c/mL) than the 25 mg (−1.8 [0.51] log 10 c/mL) and 100 mg dose groups (−1.8 [0.45] log 10 c/mL). Increasing VH-499 exposures were associated with higher viral load declines. All adverse events (AEs) were grade 1 or 2 in severity, with no trends observed in types of AEs. Each drug-related AE was only reported once. No AEs leading to withdrawal, serious AEs, or deaths were reported. There were no clinically relevant changes in clinical laboratory parameters, electrocardiograms, or vital signs. Conclusions: VH-499 monotherapy was well tolerated, had a favorable safety profile, and demonstrated highly potent antiviral activity in people living with HIV-1, with up to a mean maximum 2.2 log 10 c/mL reduction in HIV-1 RNA over 10 days. A VH-499 exposure-response relationship was established. These results support further development of VH-499 as part of a complete long-acting regimen for the treatment of HIV-1. Pharmacokinetics and Safety of Once-Yearly Formulations of Lenacapavir Vamshi Jogiraju, Pallavi Pawar, Jenna Yager, John Ling, Gong Shen, Anna Chiu, Ramesh Palaparthy, Christoph Carter, Renu Singh Gilead Sciences, Inc, Foster City, CA, USA Background: Long-acting injectables may address barriers to HIV pre-exposure prophylaxis (PrEP), such as stigma and pill burden. In a Phase 3 trial in cisgender women, twice-yearly (Q6M) subcutaneous (SC) lenacapavir (LEN) (927 mg, in two 1.5 mL injections) was safe and 100% efficacious as PrEP, with high adherence among participants. We assessed the pharmacokinetics (PK) and safety of two once-yearly (Q12M) LEN formulations. Methods: This ongoing, open-label study in healthy participants (n=20/cohort) evaluated the PK, safety, and tolerability of two intramuscular (IM) single dose 500 mg/mL LEN free acid formulations: formulations 1 and 2. Intensive PK sampling occurred from Days 1–15, and single anytime PK samples were collected at prespecified times through Day 449. LEN plasma concentrations were quantified using a validated liquid chromatography–tandem mass spectrometry method. LEN PK parameters (maximum observed concentration [C max ], trough concentration [C trough ]) were estimated using non-compartmental analysis. Safety and tolerability, including participant-reported pain scores, were assessed throughout. Results: Peak concentrations of LEN formulation 1 were achieved ~12 weeks (W) post dose with mean (coefficient of variation [CV]) C max of 290 ng/mL (61.4%) (Fig). After 12 months (M) (52W, n=13), mean (CV) C trough was 62.2 ng/mL (42.8%), and its lower bound 90% CI was 49.1 ng/mL, which were above the target concentration (mean C trough following Q6M SC LEN: 21.1 ng/mL [ Jogiraju et al, AIDS 2022 ]). Preliminary PK data for LEN formulation 2 (40W) showed similar LEN concentrations; mean C trough and the lower bound 90% CI are expected to remain above target concentration after 12M. Adverse events (AEs), including injection-site reactions (ISRs), were similar between the two cohorts; most were

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mild or moderate in severity. The most common ISR was pain (75%); pain scores were similar between cohorts. Most reported mild pain, which resolved within 1

HIV-1 RNA levels for all VH-499 dose groups declined from baseline through Day 11 (Figure). The 250 mg dose group had a greater mean (SD) maximum change in

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CROI 2025