89bio Launches Phase 3 ENLIGHTEN-Cirrhosis Trial for Pegozafermin in MASH with Compensated Cirrhosis

89bio, Inc., a biopharmaceutical company dedicated to developing innovative therapies for liver and cardiometabolic diseases, has announced the start of the ENLIGHTEN-Cirrhosis Phase 3 trial. This trial will evaluate pegozafermin, an FGF21 analog, in patients with metabolic dysfunction-associated steatohepatitis (MASH) who have compensated cirrhosis (F4).

According to Arun J. Sanyal, MBBS, M.D., director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, there is a pressing need for effective treatments for MASH patients with compensated cirrhosis. He emphasized the potential of pegozafermin to reverse fibrosis progression and mitigate the risk of liver decompensation.

The ENLIGHTEN-Cirrhosis trial is a global, randomized, double-blind, placebo-controlled study. It will involve about 760 participants who will be divided into two groups: one receiving 30mg of pegozafermin weekly and the other receiving a placebo. The primary interim endpoint of the study is the regression of fibrosis from stage F4 to an earlier stage. A subset of these patients will be evaluated at 24 months to assess fibrosis regression, potentially leading to accelerated approval in the United States and conditional approval in Europe. The trial will monitor participants until a specified number of clinical events are observed, with the final analysis focusing on clinical outcomes.

Hank Mansbach, Chief Medical Officer of 89bio, highlighted the significance of initiating the ENLIGHTEN-Cirrhosis trial. He noted that pegozafermin is the first FGF21 analog to reach Phase 3 trials for MASH patients with compensated cirrhosis. Mansbach mentioned that regulatory agencies have agreed on a potential accelerated approval pathway based on histological evidence of fibrosis regression. Previous Phase 2b ENLIVEN trials have shown improvements in liver inflammation and fibrosis, further encouraging the comprehensive Phase 3 trial.

The secondary endpoints of the trial include non-invasive tests evaluating liver health and metabolic markers. The study will use a three-panel consensus biopsy reading methodology, a technique that proved successful in the Phase 2b ENLIVEN trial. Patients will self-administer pegozafermin via a single subcutaneous injection using a planned commercial liquid formulation.

MASH, also known as nonalcoholic steatohepatitis (NASH), is a severe form of metabolic dysfunction-associated steatotic liver disease (MASLD). Characterized by fat accumulation in the liver leading to inflammation and fibrosis, MASH can eventually cause cirrhosis and other severe complications. By 2030, over 27 million people in the U.S. are projected to be affected by MASH. Approximately 20% of affected individuals may develop cirrhosis, significantly impairing liver function and possibly requiring a liver transplant to prevent liver failure.

The ENLIGHTEN program includes two Phase 3 global trials: ENLIGHTEN-Fibrosis and ENLIGHTEN-Cirrhosis. The ENLIGHTEN-Fibrosis trial focuses on non-cirrhotic MASH patients (fibrosis stage F2-F3), aiming to evaluate pegozafermin's efficacy and safety. The second trial, ENLIGHTEN-Cirrhosis, targets MASH patients with compensated cirrhosis (F4).

Pegozafermin is a glycoPEGylated analog of fibroblast growth factor 21 (FGF21), designed for treating MASH and severe hypertriglyceridemia (SHTG). FGF21 regulates energy expenditure and glucose and lipid metabolism. Clinical trials have shown pegozafermin to have direct anti-fibrotic and anti-inflammatory effects on the liver, reduce triglyceride levels, improve insulin resistance, and maintain a favorable safety profile. The U.S. FDA has granted it Breakthrough Therapy designation, and the European Medicines Agency (EMA) has given it Priority Medicines (PRIME) status for treating MASH with fibrosis.

89bio is focused on advancing pegozafermin through clinical development to provide effective treatment options for liver and cardiometabolic diseases. The company, headquartered in San Francisco, is committed to addressing the needs of patients with limited treatment options.