{"id":51438,"date":"2025-07-03T08:02:05","date_gmt":"2025-07-03T08:02:05","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=51438"},"modified":"2025-07-19T17:41:04","modified_gmt":"2025-07-19T17:41:04","slug":"clinical-studies-of-two-once-weekly-pipeline-compounds-put-on-hold-2","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/51438","title":{"rendered":"Phase 2\/3 studies put on hold for two once-weekly Gilead compounds"},"content":{"rendered":"<p><strong>Simon Collins, HIV i-Base<\/strong><\/p>\n<p><strong>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]<\/strong><\/p>\n<p>This is due to a decrease in CD4 and absolute lymphocyte counts in a subset of participants receiving both compounds together.<\/p>\n<p>The investigational compounds are\u00a0an integrase strand transfer inhibitor (INSTI) called GS-1720, and\/or a capsid inhibitor (CI) called GS-4182.<\/p>\n<p>Five studies have been affected, including the phase 2\/3 WONDERS-1 and -2 studies, plus three early phase 1 studies.<\/p>\n<p>Gilead emphasised that they are working with the regulators to understand these issues.<\/p>\n<h3>Comment<\/h3>\n<p><strong>Similar complications were reported in 2021 in early studies of islatravir, which were put on hold for similar reasons. [2, 3]<\/strong><\/p>\n<p><strong>Islatravir is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) and many of the stopped studies continued later using a lower dose.<\/strong><\/p>\n<p><strong>The negative impact on CD4 cells was linked to toxicity linked to intracellular accumulation of the active compound.<\/strong><\/p>\n<p><strong>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.\u00a0<\/strong><\/p>\n<p>Reference<\/p>\n<ol>\n<li>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).<br \/>\n<a href=\"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\">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<\/a><\/li>\n<li>HTB. Selected islatravir studies stop enrolment: further complications with important investigational drugs. (December 2021).<br \/>\n<a href=\"https:\/\/i-base.info\/htb\/41833\">https:\/\/i-base.info\/htb\/41833<\/a><\/li>\n<li>HTB. FDA further limits use of islatravir in ongoing studies. (December 2021).<br \/>\n<a href=\"https:\/\/i-base.info\/htb\/41866\">https:\/\/i-base.info\/htb\/41866<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>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 &hellip;<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-51438","post","type-post","status-publish","format-standard","hentry","category-antiretrovirals"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/51438","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=51438"}],"version-history":[{"count":12,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/51438\/revisions"}],"predecessor-version":[{"id":51934,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/51438\/revisions\/51934"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=51438"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=51438"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=51438"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}