SEATTLE — Researchers presented positive findings from early-stage clinical trials of two novel HIV inhibitors at CROI.
At a news conference, Jennifer E. Sager, PhD, a clinical pharmacologist at Gilead Sciences, presented results of a phase 1 study on the safety, tolerability and pharmacokinetics of GS-6207, a first-in-class HIV capsid inhibitor, for use as a long-acting antiretroviral agent.
In the ongoing randomized, blinded, placebo-controlled trial, 40 healthy volunteers were randomly assigned to receive placebo (n = 8) or a single shot of GS-6207 (n = 32) at 30 mg, 100 mg, 300 mg or 450 mg.
No deaths, serious adverse events, or grade 3 or 4 adverse events have been recorded, according to Sager and colleagues. They reported that most recorded adverse events have been mild — grade 1 — and resolved.
“There were no apparent patterns of adverse events across dosing cohorts,” Sager said. “With respect to [pharmacokinetics] following a subcutaneous dose in healthy volunteers, we observed prolonged GS-2607 exposure, with measurable concentrations for at least 24 weeks, and across the entire range of evaluated doses, maximum concentrations and exposure increased in a dose proportional manner. And the terminal half-life was approximately 35 days.”
Other results indicated that a dosing interval 12 weeks or longer could potentially be supported, Sager said.
Edwin DeJesus, MD, FACP, FIDSA, medical director at Orlando Immunology Center and assistant professor at University of Central Florida College of Medicine, discussed a phase 2A study of GSK 2838232, a novel maturation inhibitor.
The study measured the safety, efficacy and pharmacokinetics of the drug in once-daily 20 mg, 50 mg, 100 mg and 200 mg doses in combination with cobicistat 150 mg for 10 days. It included 33 patients infected with HIV-1 who were not on ART.
“The study showed an ascending dose-exposure and a dose-ranging activity relationship, with the highest activity seen in the 200-mg dose cohort, in which over half of the subjects achieved a greater than 1.5 log reduction from baseline HIV-1 RNA over the 10-day monotherapy dose period,” DeJesus told Infectious Disease News.
He said targeted protein binding was achieved, even at the lowest 20-mg dose. Five patients in the study had drug-related adverse events — none serious and none that led to drug interruption or study discontinuation.
“These results provide positive proof-of-concept for the development of GSK 2838232, especially if an unboosted alternative with similar or better profile is not available,” DeJesus said. – by Bruce Thiel
DeJesus E, et al. Abstract 142. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.
Sager JE, et al. Abstract 141. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.
Disclosures: DeJesus reports receiving consulting or advisor fees from Gilead Science, Janssen Therapeutics and Theratechnologies, and being on speaker’s bureaus for Gilead and Theratechnologies. Sager reports being employed by and owning stocks and stock options in Gilead.