GS-9722 Generally Safe, Well-Tolerated in Two Studies

Gilead Sciences is developing GS-9722 for use in an HIV cure regimen. The broadly neutralizing antibody (bNAb) is effector-enhanced and targets a V3 glycan motif of the HIV envelope protein.

It is derived from the bNAb PGT121 which has previously demonstrated success in vitro of immune cell-mediated killing of HIV-infected cells and has shown efficacy in monkeys infected with simian human immunodeficiency virus.

In a virtual oral abstract presentation at the Conference on Retroviruses and Opportunistic Infections (CROI 2020), investigators presented data on safety, tolerability, and efficacy, from randomized, blinded, placebo-controlled, staggered dose escalation studies featuring GS-9722.

Investigators conducted 2 studies on intravenously administered GS-9722, 1 in HIV-negative participants and 1 in virally suppressed people with HIV.

In the first study, HIV-negative participants were assigned to receive a single dose (150, 500, or 1500 mg) or multiple doses (150, 500, or 1000 mg every other week for 3 doses) or placebo.

For the second study, virally suppressed people living with HIV received either a single dose or multiple dose (every other week for 5 doses) of GS-9722 150 or 500 mg. The authors of the abstract note that this study remains ongoing, but safety and pharmacokinetics are being assessed throughout the study.

According to the investigators, 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,” the investigators wrote in their abstract. “GS-9722 t_1/2 was ~26 days, supportive of at least [every other week] dosing.”

The study team indicates that based on preliminary pharmacokinetic data, single dose GS-9722 data are similar in the virally suppressed population and HIV-negative participants.

Overall, most adverse events were considered grade 1 or 2. However in study 1, 2 participants who received multiple doses of 1000mg discontinued the study drug as a result of drug-related adverse events. One individual had thrombocytopenia, considered a grade 3 serious adverse event, and the other individual had a grade 2 adverse event of infusion-related reaction.

In study 2, 1 individual who received a 150 mg single dose had an unrelated grade 2 serious adverse event of small intestinal obstruction. Thus far, no other serious adverse events or adverse events related to study drug discontinuation have been reported.

“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 2 populations,” the investigators wrote.

The team concludes that based on these data, GS-9722 should continue to be evaluated as part of a combination therapy for HIV cure.

The abstract, Safety & pharmacokinetics of GS-9722 in HIV negative participants and people with HIV, was presented on Monday, March 9, 2020, in a virtual session at CROI 2020.