Trial Data Released for Investigational HIV-1 Capsid Inhibitor

GS-6207 is a first-in-class investigational HIV-1 capsid inhibitor with the potential to be a long-acting therapy for people living with HIV.

Data from clinical and preclinical studies on the use of GS-6207 were presented via 3 posters at the annual Conference on Retroviruses and Opportunistic Infections (CROI 2020).

Poster 1: Dose-Response Relationship

A randomized, double-blind phase 1b dose-response study evaluated GS-6207 in terms of safety, pharmacokinetics, and antiviral activity.

The study team randomized 39 people living with HIV to receive either placebo or a single subcutaneous dose of GS-6207 at 20, 50, 450, or 750 mg. The primary end point of the study was maximum reduction of plasma HIV-1 RNA through ten days after dosing.

The 750mg cohort is still enrolling. All participants in the 450 and 20 mg cohorts who received GS-6207 had significant reductions in HIV-1 RNA by day 10 relative to placebo.

“The maximum reduction in HIV-1 RNA through Day 10 ranged from 0.8 to 3.0 log₁₀ copies/mL. The predicted maximum HIV-1 RNA reduction was 2.2 log₁₀ copies/mL,” the poster authors wrote.

The capsid inhibitor was generally well tolerated and safe. Most common adverse events were mild injection site reactions.

Poster 2: Pharmacokinetics, Food Effect and Safety

In a randomized phase 2 study, investigators tested the safety, pharmacokinetics, and food effect of oral GS-6207 in HIV-negative participants.

In the first study cohort, 40 participants were randomized to either placebo or a single dose of oral GS-6207 at 50, 300, 900, or 1800 mg. The second study cohort featured 16 participants who received a single 300 mg dose of GS-6207 after either a high-fat or lighter meal.

Interim results were presented. The treatment was generally safe and well tolerated, with common adverse events reported being back pain or headache.

The half-life of the inhibitor was around 12 days, and the pharmacokinetic profile was not impacted by either the high or low fat meal. This suggests the agent can be developed without regard to food impact.

Poster 3: Absence of GS-6207 Phenotypic Resistance in HIV Gag Cleavage Site and Other Mutants

A preclinical study examined the impact of gag cleavage site mutations on the antiviral activity of GS-6207. The study also explored the effect of mutations associated with resistance to other classes of HIV drugs such as nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors.

In vitro activity of GS-6207 was not impacted by mutations associated with resistance to the 4 primary classes of HIV drugs or by mutations at the HIV gag cleavage site.

“The results support the evaluation of GS-6207 in people living with HIV with multi-class resistance,” the poster authors wrote.

These posters were virtually presented at CROI 2020 on Wednesday, March 11.