LBPEB13

Title

Safety and antiviral activity over 10 days following a single dose of subcutaneous GS-6207, a first-in-class, long-acting HIV capsid inhibitor in people living with HIV

Presenter

Eric S. Daar

Authors

E.S. Daar¹, C. McDonald², G. Crofoot³, P. Ruane⁴, G. Sinclair⁵, H. Patel⁶, J. Sager⁶, Y.-P. Liu⁶, D.M. Brainard⁶, R.H. Hyland⁶, M. Rhee⁶

Institutions

¹Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, United States, ²Tarrant County Infectious Disease Associates, Fort Worth, United States, ³The Crofoot Research Center, Houston, United States, ⁴Ruane Clinical Research Group Inc, Los Angeles, United States, ⁵AIDS Arms Inc. DBA Prism Health North Texas, Dallas, United States, ⁶Gilead Sciences, Foster City, United States

Background: GS-6207 is a novel, long-acting inhibitor of HIV-1 capsid function. In a previous study in HIV-negative volunteers, a single dose of subcutaneous (SC) GS-6207 at 30, 100, 300, or 450 mg was well tolerated and maintained systemic exposure ≥24 weeks.
Methods: This ongoing, phase 1b, double-blinded, placebo-controlled, dose-ranging, randomized (3:1; n=8/group) people living with HIV who were capsid- and integrase-naive and ART-naive (or had not received ART 12 weeks before entry). Participants received a single SC dose of GS-6207 (20, 50, 150, 450, or 750 mg) or placebo. Primary endpoint was maximum reduction of plasma HIV-1 RNA through day 10. Safety was assessed using laboratory tests and adverse event (AE) reporting. On day 10, all participants initiated single-tablet regimen bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). Herein, we present efficacy (through day 10) and blinded safety (through at least day 16) data for the 50, 150, and 450 mg cohorts.
Results: Demographics and baseline characteristics were similar across groups. Significant reductions in plasma HIV-1 RNA by day 10 were observed for all groups, compared with placebo (p< 0.0001). Mean maximum decrease in HIV-1 RNA in each group ranged from 1.76 to 2.20 log₁₀ copies/mL (figure). No serious AEs, AEs leading to discontinuation, Grade 3 or 4 AEs, or clinically relevant Grade 3 or 4 laboratory abnormalities were reported. Most common AEs were mild or moderate injection site reactions (63%; 15 of 24). Available data from remaining cohorts will be presented.
Conclusions: These preliminary data demonstrate the first proof-of-concept for in vivo antiviral activity of capsid inhibition. Following a single SC dose, potent antiviral activity was observed in all participants who received GS-6207 at 50, 150, or 450 mg through day 10. GS-6207 was generally safe and well tolerated. These results support further evaluation of GS-6207 as a long-acting antiretroviral agent in people living with HIV.

[Mean (95% CI) Changes from Baseline in HIV-1 RNA (log₁₀ copies/mL)]