Clinical studies of two once-weekly pipeline compounds put on hold
27 June 2025. Related: Early access, Antiretrovirals.
Simon Collins, HIV i-Base
On 10 June 2025, Gilead Sciences announced that the US FDA has put studies of two investigational HIV compounds, from two different drug classes, to be put on hold. [1]
This is due to a decreases 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 (CaI) called GS-4182.
Five studies have been affected, including the phase 2/3 WONDERS-1 and -2 studies plus three ealy phase 1 studies.
Gilead emphasised that they are working with regulation
Comment
Similar circumstances were reported in 2021 in early studies of islatravir that were put on for similar complications. [2, 3]
Islatravir is an nucleoside reverse transcriptase translocation inhibitor (NRTTI) and many of the stopped studies later continued 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 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. HTB (December 2021).
https://i-base.info/htb/41833 - HTB. FDA further limit use of islatravir in ongoing studies. (December 2021),
https://i-base.info/htb/41866