89bio Initiates Phase 3 ENLIGHTEN-Cirrhosis Trial of Pegozafermin in Metabolic Dysfunction-Associated Steatohepatitis (MASH) Patients with Compensated Cirrhosis

Core Insights - 89bio, Inc. has initiated the ENLIGHTEN-Cirrhosis trial, marking pegozafermin as the first FGF21 analog to enter a Phase 3 trial for MASH patients with compensated cirrhosis (F4) [1][3] - The trial aims to evaluate the efficacy of pegozafermin in reversing fibrosis, with potential for accelerated approval based on histological evidence [2][3] Company Overview - 89bio is a clinical-stage biopharmaceutical company focused on developing therapies for liver and cardiometabolic diseases, particularly MASH and severe hypertriglyceridemia [7] - The company is headquartered in San Francisco and is dedicated to advancing its lead candidate, pegozafermin, through clinical development [7] Trial Details - The ENLIGHTEN-Cirrhosis trial is a global, randomized, double-blind, placebo-controlled study enrolling approximately 760 patients, with a 1:1 randomization to receive either 30mg of pegozafermin weekly or a placebo [2][5] - The primary endpoint is defined as fibrosis regression from F4 to an earlier stage, with an interim analysis at 24 months to support potential accelerated approval in the U.S. and conditional approval in Europe [2][3] Disease Context - MASH, also known as nonalcoholic steatohepatitis (NASH), is a chronic condition characterized by liver fat accumulation, inflammation, and potential progression to fibrosis and cirrhosis [4] - By 2030, MASH is projected to affect over 27 million people in the U.S., with approximately 20% of patients potentially developing cirrhosis [4] Pegozafermin Profile - Pegozafermin is a glycoPEGylated analog of FGF21, demonstrating anti-fibrotic and anti-inflammatory effects, along with improvements in triglyceride levels and insulin resistance [6] - The drug has received Breakthrough Therapy designation from the FDA and Priority Medicines status from the EMA for treating MASH with fibrosis [6] ENLIGHTEN Program - The ENLIGHTEN program consists of two Phase 3 trials: ENLIGHTEN-Cirrhosis for compensated cirrhosis (F4) and ENLIGHTEN-Fibrosis for non-cirrhotic MASH (F2-F3) [5] - The co-primary endpoints for ENLIGHTEN-Fibrosis include a one-point improvement in fibrosis and MASH resolution without worsening fibrosis, assessed at week 52 [5]