Gilead has posted early data on a first-in-class inhibitor of HIV-1 capsid function it thinks could play a role in long-acting combination therapies. The data supported the progress of the asset, GS-6207, into a phase 1b trial in HIV-1 infected adults.
Teams at Gilead, Pfizer and other research groups have spent years looking into the capsid that cloaks the genetic material of HIV. As the capsid is vital to the virus and the RNA that encodes for it is fairly stable, disrupting the shell could deliver a critical blow to HIV without running the risk that resistance will quickly emerge.
Gilead is now set to test that idea in the clinic. The advance of GS-6207 into patients was supported by data from healthy volunteers Gilead presented this week at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI).
The 40-subject study gave single, subcutaneous doses of GS-6207 of up to 450 mg. Having gathered 20 weeks of data on the 30 mg cohort and four weeks on the 450 mg arm, Gilead is yet to see any grade 3 or above adverse events. Most adverse events were mild and resolved.
Gilead also has enough data from the two lower-dose cohorts to estimate the pharmacokinetic parameters of GS-6207. That has backed up Gilead’s belief that factors such as low human clearance will make GS-6207 suitable for use in extended-release formulations. The current data suggests a dosing interval of three months or more is possible.
With a favorable dosing schedule and characteristics that decrease the risk of resistance, GS-6207 could form part of a successful long-acting combination therapy. But Gilead is still some ways from generating the data to validate that hypothesis.
Gilead shared more in vitro data on GS-6207 at CROI, but the bigger efficacy tests are just getting started. Gilead began enrolling the first of a planned 32 HIV patients in a phase 1b in December and disclosed the activation of more sites this week. The study is looking at the maximum reduction in plasma HIV-1 RNA over the 10 days after they receive GS-6207.