CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

203

VH3810109 (N6LS) Efficacy and Safety in Adults Who Are Virologically Suppressed: The EMBRACE Study Peter Leone 1 , Babafemi Taiwo 1 , Margaret Gartland 1 , Paul Wannamaker 2 , Annie F. Luetkemeyer 3 , Charlotte-Paige M. Rolle 4 , Christopher J. Bettacchi 5 , William Towner 6 , Michael Warwick-Sanders 7 , Riccardo D’Agostino 7 , Rulan Griesel 2 , Chelsea MacFarlane 1 , David Dorey 8 , Sherene Min 1 , Jan Losos 1 1 ViiV Healthcare, Durham, NC, USA, 2 ViiV Healthcare, Brentford, UK, 3 University of California San Francisco, San Francisco, CA, USA, 4 Orlando Immunology Center, Orlando, FL, USA, 5 North Texas Infectious Diseases Consultants, Dallas, TX, USA, 6 Kaiser Permanente Southern California, Pasadena, CA, USA, 7 GSK plc, Brentford, UK, 8 GSK plc, Mississauga, ON, Canada Background: VH3810109 (N6LS) is a broadly neutralizing CD4-binding site antibody being developed for long-acting HIV-1 therapy. N6LS was well tolerated and efficacious in participants with HIV-1 naive to treatment when administered intravenously (IV) or subcutaneously (SC) in the proof-of-concept phase 2a BANNER study. In the phase 1 SPAN study, single-dose N6LS given IV (60 mg/kg) or SC (3000 mg) with recombinant human hyaluronidase PH20 (rHuPH20) showed a good safety profile in adults without HIV. Using the same doses from SPAN, the EMBRACE study evaluated the efficacy, safety, and tolerability of N6LS every 4 months + long-acting intramuscular cabotegravir (CAB LA) monthly for maintenance of HIV-1 suppression. Methods: EMBRACE is a phase 2b, randomized, open-label, multicenter study (45 sites; US and Puerto Rico) in adults with screening HIV-1 RNA <50 c/mL and phenotypic sensitivity to N6LS (90% inhibitory concentration [IC 90 ] ≤2.0 µg/ mL). Participants were randomized 2:2:1 to N6LS 60 mg/kg IV + CAB LA, N6LS 3000 mg + rHuPH20 SC + CAB LA, or to continue their pre-baseline standard of-care (SOC) regimen. The primary endpoint was plasma HIV-1 RNA ≥50 c/mL at Month 6 (FDA Snapshot algorithm). Results: Of 125 participants randomized, median (range) age was 53 (22-69) years and 83% were male; 63% identified as White, 28% as Black or African American, and 43% as Hispanic or Latin American. Proportions with plasma HIV-1 RNA ≥50 c/mL at Month 6 were 2/50 (4%) with N6LS 60 mg/kg IV, 3/49 (6%) with N6LS 3000 mg SC + rHuPH20, and 0/26 (0%) with SOC (Table). Through Month 6, confirmed virologic failure (CVF) occurred in 2 participants receiving N6LS 60 mg/kg IV, 2 receiving N6LS 3000 mg SC + rHuPH20, and 0 receiving SOC. Of 3 participants with data available at CVF, 1 had N6LS IC 90 >2 µg/mL and none had integrase resistance mutations. N6LS was well tolerated when given IV or SC + rHuPH20, with AEs leading to withdrawal occurring in 3/49 receiving SC + rHuPH20 and no N6LS/CAB-related serious AEs reported. Grade ≥3 N6LS-related infusion site reactions (ISRs) were reported in 0/50 (0%) participants receiving N6LS 60 mg/kg IV and 7/49 (14%) receiving N6LS 3000 mg SC + rHuPH20; mean (SD) duration of all ISRs was 2.0 (0.8) and 6.4 (5.2) days with N6LS dosed IV or SC + rHuPH20, respectively. Conclusions: N6LS administered IV or SC + rHuPH20 every 4 months in combination with monthly CAB LA maintained viral suppression in most adults who were sensitive to N6LS at baseline, with tolerability favoring IV N6LS.

204A Switch to DOR/ISL (100/0.25 mg) QD From BIC/FTC/TAF: A Blinded Phase III Study in Adults With HIV-1 Michelle Fox 1 , Anthony M. Mills 2 , Moti Ramgopal 3 , Christopher J. Bettacchi 4 , Olayemi Osiyemi 5 , Federico Hinestrosa 6 , Gordon E. Crofoot 7 , Harold P. Katner 8 , Hiroyuki Gatanaga 9 , Margaret Johnson 10 , Feng-Hsiu Su 1 , Alice Xu 1 , Luisa Stamm 1 , Amy E. Colson 11 , Rima Lahoulou 12 1 Merck & Co, Inc, Rahway, NJ, USA, 2 Men's Health Foundation, Los Angeles, CA, USA, 3 Midway Immunology and Research Center, Fort Pierce, FL, USA, 4 North Texas Infectious Diseases Consultants, Dallas, TX, USA, 5 Triple O Research Institute, West Palm Beach, FL, USA, 6 Orlando Immunology Center, Orlando, FL, USA, 7 The Crofoot Research Center, Houston, TX, USA, 8 Mercer University, Macon, GA, USA, 9 National Center for Global Health and Medicine, Tokyo, Japan, 10 Royal Free London NHS Foundation Trust, London, UK, 11 Community Resource Initiative, Boston, MA, USA, 12 MSD France, Puteaux, France Background: Doravirine (DOR), an NNRTI, and islatravir (ISL), an investigational nucleoside reverse transcriptase translocation inhibitor, have complementary mechanisms of action and resistance profiles. MK-8591A-052 is an ongoing phase 3 study evaluating the efficacy and safety of switching from bictegravir/ emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) to DOR/ISL (100/0.25 mg), a once-daily single-tablet regimen. Declines in CD4 T-cell and lymphocyte counts were seen with higher ISL doses. Methods: In this double-blind, non-inferiority study (NCT05630755) adults with HIV-1, virologic suppression for ≥3 months on BIC/FTC/TAF, and no history of treatment failure or known resistance to DOR were randomized (2:1) to switch to DOR/ISL (100/0.25 mg) or continue BIC/FTC/TAF. Primary efficacy endpoint was % of participants with HIV-1 RNA ≥50 c/mL at week 48 (FDA snapshot; non inferiority margin 4%). Discontinuation was required for confirmed decline in total lymphocytes (≥30% and to <1.0 x 109/L) or in CD4 T-cell count (≥30% and to <350 cells/mm 3 from baseline ≥350 or to <200 from baseline ≤349). Results: We treated 513 participants: 342 switched to DOR/ISL (100/0.25 mg), 171 continued BIC/FTC/TAF. Mean age was 47.6 (±12.9) yrs, 21.4% were female at birth, 60.8% were White, 30.8% were Black/African American, and 22.8% were Latine. At week 48, HIV-1 RNA was ≥50 c/mL in 5 (1.5%) participants on DOR/ISL and 1 (0.6%) on BIC/FTC/TAF (difference 0.9%, 95% CI -1.9, 2.9; CI upper bound <4%), demonstrating non-inferiority of DOR/ISL to BIC/FTC/TAF. HIV-1 RNA was <50 c/mL in 91.5% of participants on DOR/ISL and 94.2% on BIC/FTC/ TAF. One participant on DOR/ISL discontinued due to lack of efficacy with no on treatment resistance detected at the time of viremia. Rates of AEs (74.6% DOR/ ISL, 71.3% BIC/FTC/TAF), drug-related AEs (10.2%, 9.4%), and discontinuations due to AEs (2.9%, 1.8%) were similar between groups. There were no between‑group differences in mean change in CD4 T-cell or total lymphocyte count at week 48. Two participants on DOR/ISL (0.6%) and one on BIC/FTC/TAF (0.6%) discontinued due to decrease in CD4 T-cell or total lymphocyte count. Conclusions: DOR/ISL (100/0.25 mg) maintained viral suppression and was non-inferior to BIC/FTC/TAF at week 48. DOR/ISL was well tolerated with a similar safety profile to BIC/FTC/TAF and did not adversely affect lymphocytes.

Oral Abstracts

58

CROI 2025