Capsid inhibitor GS-6207 shows potential for 3-monthly injections

28 March 2019. Related: Conference reports, Antiretrovirals, CROI 26 (Retrovirus) 2019.

Simon Collins, HIV i-Base

Early results study for a long-acting injection formulation of the capsid inhibitor GS-6207 were presented by Jennifer Sage from Gilead Sciences.

This was a phase 1 dose escalation study in 40 HIV negative volunteers.

Capsid inhibitors are potentially active at several stages of the viral lifecycle including early uncoating once HIV has infected a CD4 cell and at a late stage when new virus is being reassembled.

GS-6207 is a highly potent molecule that is formulated as a long-acting sub-cutaneous injection.

Forty participants were randomised to one of four single doses: 30 mg, 100 mg, 300 mg and 450 mg with 8 active and 2 placebo recipients in each arm. Three injections were required for the two highest doses.

Approximately 70% of the participants were male and 70% were white. Mean age was about 35 years (range 21 to 44).

Pharmacokinetic results showed prolonged exposure following the single exposure, with drugs levels sustained for over 24 weeks. Drug levels were dose related but similar exposures were seen for the 300 mg and 450 mg groups.

All doses for the 100 mg, 300 mg and 450 mg group remained above the protein adjusted EC95 at week 12 that continued out to week 24 for the 450 mg group.

There were no serious adverse events, most grade 1.

In vitro activity data for GS-6207 reporting significantly greater potency compared to current ARVs (including dolutegravir) with activity against resistance to NRTI, NNRTI, PI and integrase inhibitor classes was also presented in a poster. [2]

GS-6207 is already in phase 1 studies in HIV positive people. [3]

References

1. Sage JE et al. Safety and PK of subcutaneous GS-6207, a novel HIV-1 capsid inhibitor. Conference on Retroviruses and Opportunistic Infections (CROI), 4-7 March 2019, Seattle. Oral abstract 141.
   http://www.croiconference.org/sessions/safety-and-pk-subcutaneous-gs-6207-novel-hiv-1-capsid-inhibitor (abstract)
   http://www.croiwebcasts.org/p/2019croi/141 (webcast)
2. Yant SR et al. GS-6207, a potent and selective first-in-class long-acting HIV-1 capsid inhibitor. Conference on Retroviruses and Opportunistic Infections (CROI), 4-7 March 2019, Seattle. Poster 480.
   http://www.croiconference.org/sessions/gs-6207-potent-and-selective-first-class-long-acting-hiv-1-capsid-inhibitor (abstract)
3. ClinicalTrials.gov. Safety, pharmacokinetics, and antiviral activity of GS-6207 administered subcutaneously in HIV-1 infected adults.
   https://clinicaltrials.gov/ct2/show/NCT03739866