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SAFETY & PHARMACOKINETICS OF GS-9722 IN HIV-NEGATIVE PARTICIPANTS AND PEOPLE WITH HIV
Peter Ruane1, Eric Daar2, Kimberly Workowski3, Rebecca Begley4, Rita Humeniuk4, Tariro Makadzange4, Steve K. West4, Hui Liu4, Yizhao Li4, John Ling4
1Peter J Ruane, MD Inc, Los Angeles, CA, USA,2Harbor–UCLA Medical Center, Torrance, CA, USA,3Emory University, Atlanta, GA, USA,4Gilead Sciences, Inc, Foster City, CA, USA,5University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,6MedStar Health, Washington, DC, USA,7Orlando Immunology Center, Orlando, FL, USA
GS-9722 is an effector-enhanced, broadly neutralizing antibody (bNAb) targeting a V3 glycan motif of the HIV envelope protein which is being developed for use in a HIV cure regimen. GS-9722 is a derivative of the bNAb PGT121 which has demonstrated immune cell-mediated killing of HIV-infected cells in vitro and efficacy in SHIV-infected monkeys. The safety, tolerability and pharmacokinetics (PK) of GS-9722 administered intravenously (IV; 30 infusion) were evaluated in a first-in-human study in HIV-negative participants (Study 1) and in virally suppressed people with HIV (VS-PWH; Study 2).
Two randomized, blinded, placebo-controlled, staggered dose escalation studies were conducted. In Study 1, HIV-negative participants received single dose (SD; 150, 500, or 1500 mg) or multiple doses (MD; 150, 500, or 1000 mg every other week [QOW] for three doses) of GS‑9722 (n=6/cohort) or placebo (n=2/cohort). In Study 2, VS-PWH received SD or MD (QOW for five doses) GS-9722 150 or 500 mg (n=6/cohort) or placebo (n=2/cohort). Study 1 has completed; Study 2 is ongoing. Safety and PK are assessed throughout each study.
In Studies 1 and 2, 45 of 49 and 32 of 32 participants completed treatment, respectively. In Study 1, dose-proportional increases in GS-9722 AUC and Cmax were observed (Table). GS-9722 t1/2 was ~26 days, supportive of at least QOW dosing. Preliminary SD PK data in VS-PWH are similar to HIV-negative participants (Table); PK analysis in MD VS-PWH cohorts is ongoing. Most AEs were grade 1 or 2. In Study 1, two participants discontinued study drug due to AEs (1000 mg; MD), both of which were considered related to study drug; one participant had a grade 3 SAE of thrombocytopenia and the other had a grade 2 AE of infusion related-reaction. In Study 2, one participant had a grade 3 unrelated SAE of small intestinal obstruction (150 mg; SD). No other SAEs or AEs leading to study drug discontinuation were reported to date.
These studies demonstrate that GS-9722 is generally safe and well tolerated in HIV-negative participants and VS-PWH, with similar single dose PK in the two populations. These data support ongoing evaluation of GS-9722 as part of a combination therapy for HIV cure.