Gilead’s Phase 1a clinical trial evaluated the safety, tolerability, and pharmacokinetics (PK) of single ascending doses of GS-1720, a novel oral long-acting integrase strand transfer inhibitor (INSTI), in healthy adults without HIV-1. Presented at this year’s IDWeek, the study demonstrated that GS-1720 has the potential to be a transformative treatment option for people living with HIV, with primary endpoints indicating favorable pharmacokinetic properties.
Jared Baeten, MD, PhD, lead of the virology therapeutic area at Gilead Sciences, emphasized the potential impact of GS-1720, stating, “For people living with HIV, this could be transformative, as having to take medicines once a week instead of every day would improve adherence and persistence—the ability to consistently take medications over a long time.”
The results indicated that GS-1720 demonstrated nonlinear pharmacokinetics, with maximum concentration (Cmax) and AUCinf increasing less than dose proportionally showing 1.6- to 2.2-fold increases in Cmax and 1.8- to 2.5-fold increases in AUCinf (area under the concentration-versus-time curve extrapolated to infinity) with each three-fold dose increase. The median time to maximum concentration was 4 hours, and the terminal half-life was approximately 9.3 days.
The study included 40 participants who were randomly assigned to receive escalating doses of GS-1720 (50, 150, 450, or 1350 mg; n=8 per cohort) or placebo (n=2 per cohort) under fasting conditions. Participants were monitored for up to 70 days for safety and pharmacokinetic outcomes.
Regarding safety, the assessment revealed that GS-1720 was generally well tolerated, with no serious adverse events (AEs), Grade 3/4 AEs, or clinically significant laboratory abnormalities observed across any dose levels. Additionally, no dose-related effects on the incidence or nature of AEs were noted. Baeten added, “This study aimed to understand how it would behave in humans. By understanding this, we aimed to determine what an appropriate dose would be for those living with HIV as part of their treatment.”
The population pharmacokinetic model developed during the study illustrated GS-1720’s absorption and disposition, featuring a two-compartment model with dose-dependent saturation. This model informed optimal dosing frequency and levels for subsequent Phase 1b studies, suggesting that dosing on Days 1 and 2 would be preferable over Day 1-only dosing.
Baeten further explained, “This study also provided insights into safety in a population, both at doses lower and higher than what one might typically expect to choose. Based on these data, along with other studies involving GS-1720 in persons living with HIV, we can identify the dose to move into later phase studies. In fact, GS-1720, in combination with another investigational agent, is currently in Phase 2 for HIV treatment.”
Overall, GS-1720 demonstrated a favorable safety profile and nonlinear pharmacokinetics in this healthy cohort, supporting its continued development as a long-acting treatment option for HIV-1. Further investigations, including multiple ascending dose cohorts, will provide additional insights into the drug’s efficacy and safety.
