Phase 2/3 studies put on hold for two once-weekly Gilead compounds
3 July 2025. Related: Antiretrovirals.
Simon Collins, HIV i-Base
On 10 June 2025, Gilead Sciences announced that the US FDA had put studies of two investigational HIV compounds from two different drug classes on hold. [1]
This is due to a decrease in CD4 and absolute lymphocyte counts in a subset of participants receiving both compounds together.
The investigational compounds are an integrase strand transfer inhibitor (INSTI) called GS-1720, and/or a capsid inhibitor (CI) called GS-4182.
Five studies have been affected, including the phase 2/3 WONDERS-1 and -2 studies, plus three early phase 1 studies.
Gilead emphasised that they are working with the regulators to understand these issues.
Comment
Similar complications were reported in 2021 in early studies of islatravir, which were put on hold for similar reasons. [2, 3]
Islatravir is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) and many of the stopped studies continued later using a lower dose.
The negative impact on CD4 cells was linked to toxicity linked to intracellular accumulation of the active compound.
This might be linked to the mechanism of extended long-acting drugs rather than a direct toxicity of the compounds themselves, but further research is needed.
Reference
- Gilead press release. Gilead provides update on clinical studies evaluating GS-1720 and/or GS-4182 for the treatment of HIV-1 infection. (10 June 2025).
https://www.gilead.com/company/company-statements/2025/gilead-provides-update-on-clinical-studies-evaluating-gs-1720-and-or-gs-4182-for-the-treatment-of-hiv-1-infection - HTB. Selected islatravir studies stop enrolment: further complications with important investigational drugs. (December 2021).
https://i-base.info/htb/41833 - HTB. FDA further limits use of islatravir in ongoing studies. (December 2021).
https://i-base.info/htb/41866