lenacapavir pro-drug (GS‑4182) / Gilead - LARVOL DELTA

FDA slaps clinical hold on multiple Gilead HIV combo therapy trials, shares fall (FierceBiotech) - "Gilead has been hit with a clinical hold from the FDA for five tests of its experimental HIV combination treatment amid safety concerns...the California Big Pharma said trials of GS-1720, an investigational integrase strand transfer inhibitor, and/or GS-4182, an investigational capsid inhibitor, had been put on a full FDA hold. The drugs had been in two phase 2/3 tests known as WONDERS-1 and WONDERS-2, as well as three earlier phase 1 studies...The hold comes after “the identification of a safety signal of decreases in CD4+T-cell (CD4) and absolute lymphocyte counts in a subset of participants receiving the combination of GS-1720 and GS-4182,” Gilead said in its statement."

FDA event • Trial suspension • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated (clinicaltrials.gov) - P2/3 | N=675 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed (clinicaltrials.gov) - P2/3 | N=675 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Effect of acid‐reducing agents on the pharmacokinetics of oral GS‐4182 (HIV-Glasgow 2024) - "LEN exposure with and without esomeprazole Plasma LEN PK parameter GS-4182 400 mg + esomeprazole 40 mg (n = 12) GS-4182 400 mg (reference cohort) (n = 9) GLSM ratio, % (90% CI) Geometric mean AUC0-168h (%GCV), hour*ng/ml 6080 (45.1) 4810 (85.1) 126% (81.2−197) Geometric mean Cmax (%GCV), ng/ml 50.7 (54.4) 44.7 (141) 113% (62.5−206) Median Tmax (Q1, Q3), hours 12.0 (10.0, 48.0) 12.0 (4.0, 24.1) − Abbreviations: AUC0-168h, area under the concentration versus time curve from 0 to 168 hours; Cmax, maximum observed concentration; CI, confidence interval; GCV, geometric coefficient of variation; GLSM, geometric-least squares means; LEN, lenacapavir; PK, pharmacokinetics; Tmax, time to maximum concentration. LEN exposure following a single oral dose of GS-4182 400 mg was similar with and without esomeprazole coadministration. Therefore, GS-4182 could be administered without regard to ARA use."

PK/PD data • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated (clinicaltrials.gov) - P2/3 | N=675 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated (clinicaltrials.gov) - P2/3 | N=675 | Not yet recruiting | Sponsor: Gilead Sciences

Combination therapy • New P2/3 trial • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed (clinicaltrials.gov) - P2/3 | N=675 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed (clinicaltrials.gov) - P2/3 | N=675 | Not yet recruiting | Sponsor: Gilead Sciences

Combination therapy • New P2/3 trial • Human Immunodeficiency Virus • Infectious Disease

Safety and pharmacokinetic profile of single and multiple ascending doses of GS-4182, an oral prodrug of lenacapavir, in participants without HIV-1 (AIDS 2024) - "GS-4182 demonstrated favorable LEN PK, with LEN exposure following oral GS-4182 600 mg administration approximately double compared with the equivalent dose of oral LEN. GS-4182 was well tolerated with a favorable safety profile, supporting its further development as a QW oral agent for HIV-1 treatment."

Clinical • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Nonclinical profile of GS-4182, a once-weekly oral prodrug of the HIV-1 capsid inhibitor lenacapavir in clinical development (AIDS 2024) - "LEN prodrug GS-4182 exhibits a favorable nonclinical profile that supports its continued clinical development as a component of an optimized once-weekly oral regimen for the treatment of HIV-1 infection."

Clinical • Gastrointestinal Disorder • Human Immunodeficiency Virus • Infectious Disease