cilofexor/firsocostat (GS-9674/GS-0976) / Gilead - LARVOL DELTA

A RANDOMIZED, PLACEBO-CONTROLLED, PHASE 2 STUDY OF THE SAFETY AND EFFICACY OF COMBINATION TREATMENT WITH SEMAGLUTIDE, CILOFEXOR AND FIRSOCOSTAT IN PATIENTS WITH COMPENSATED CIRRHOSIS DUE TO METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (WAYFIND) (AASLD 2025) - P2 | "SEMA+CILO/FIR did not achieve the primary endpoint of fibrosis improvement compared with PBO based on pathologist review. However, SEMA-containing regimens achieved MASH resolution and CILO/FIR achieved fibrosis improvement compared with PBO. Interestingly, PathAI showed clinical benefit with SEMA+CILO/FIR, suggesting that combination therapies should be explored for MASH."

Clinical • P2 data • Constipation • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Comparison of Pharmacological Therapies for Metabolic Dysfunction-Associated Steatohepatitis: Systematic Review and Network Meta-analysis (APASL 2025) - "For the co-primary endpoint of fibrosis improvement without MASH resolution, pegozafermin, cilofexor + firsocostat, survodutide, obeticholic acid, tirzepatide, and resmetirom were significantly better than placebo in improving ≥ 1 fibrosis stage without worsening MASH. Pegozafermin (SUCRA: 90.18), cilofexor plus firsocostat (SUCRA: 82.82), and cilofexor plus selonsertib (SUCRA: 79.62) were ranked the most effective interventions. For the co-primary endpoint of MASH resolution without worsening fibrosis, pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, and lanifibranor were significantly better than placebo... This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design."

Retrospective data • Review • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis. (PubMed, Hepatology) - "This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Study of Semaglutide, and Cilofexor/Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=457 | Completed | Sponsor: Gilead Sciences | Active, not recruiting ➔ Completed

Trial completion • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

COMPARATIVE EFFICACY OF PHARMACOLOGIC THERAPIES FOR MASH IN REDUCING LIVER FAT CONTENT: SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (AASLD 2024) - "By comparison of absolute MRI-PDFF decline at 24 weeks, aldafermin (SUCRA: 83.65), pegozafermin (SUCRA: 83.46), and pioglitazone (SUCRA: 71.67) were the most efficacious interventions. Efinopegdutide (SUCRA: 67.02), semaglutide + firsocostat (SUCRA: 62.43), and pegbelfermin (SUCRA: 61.68) were the most efficacious interventions for achieving ≥30% decline in MRI-PDFF at 24 weeks...Efruxifermin, aldafermin and pegozafermin were the most efficacious for MRI-PDFF decline at 12 weeks by both the absolute decline and achieving ≥30% decline in MRI-PDFF. At 48 weeks, Cilofexor + firsocostat, selonternib + firsocostat and cilofexor were most efficacious in absolute reduction in MRI-PDFF, while semglutide, tropifexor and tropifexor + cenicriviroc were most efficacious in achieving ≥30% decline in MRI-PDFF... This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat as assessed by MRI-PDFF. These data may help inform the design and..."

Retrospective data • Review • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Pharmacokinetics and Safety of Cilofexor and Firsocostat in Healthy Japanese and Non-Japanese Participants. (PubMed, J Clin Pharmacol) - P2 | "Both study drugs were well tolerated with no clear differences in adverse events or laboratory abnormalities between Japanese and non-Japanese participants. The approximate 2-fold exposure difference of firsocostat between Japanese and non-Japanese participants at the 20 mg dose does not warrant dose reduction given the previously established safety and tolerability of once-daily doses of firsocostat up to 200 mg."

Journal • PK/PD data • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Study of Semaglutide, and the Fixed-Dose Combination of Cilofexor and Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=457 | Active, not recruiting | Sponsor: Gilead Sciences

Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis