89bio, Inc. announced the initiation of its Phase 3 ENLIGHTEN Program evaluating the efficacy and safety of pegozafermin in patients with metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH). ENLIGHTEN-Fibrosis, the first of two Phase 3 trials in the program, has initiated and is evaluating non-cirrhotic MASH patients with fibrosis stage F2-F3. ENLIGHTEN-Fibrosis is a global Phase 3, randomized, double-blind, placebo-controlled trial of pegozafermin for the treatment of patients with biopsy-confirmed non-cirrhotic MASH.

Approximately 1,000 patients are expected to be randomized in a 1:1:1 ratio to receive either 30mg of pegozafermin administered weekly, 44mg administered every two weeks, or placebo. The co-primary endpoints are a one-point or greater improvement in fibrosis with no worsening of MASH, and MASH resolution with no worsening of fibrosis. The co-primary endpoints will be assessed at week 52 and are intended to support a filing for accelerated approval in the U.S. and conditional approval in Europe in non-cirrhotic patients.

Patients are expected to continue to be treated beyond the 52-week assessment through outcomes to support full approval. Key secondary endpoints include additional histological endpoints, noninvasive tests (NITs) and metabolic and lipid assessments. The trial is designed to employ a three-panel consensus biopsy reading methodology, which was successfully utilized in the ENLIVEN trial.

Patients will self-administer pegozafermin using the planned commercial liquid formulation delivered as a single subcutaneous injection. The ENLIGHTEN program is comprised of two Phase 3 global, multi-center, randomized, double-blind, placebo-controlled trials, evaluating the efficacy and safety of pegozafermin in patients with MASH. The ENLIGHTEN-Fibrosis study, the first of two Phase 3 trials in the program, is expected to enroll approximately 1,000 patients with non-cirrhotic MASH (fibrosis stage F2-F3) to evaluate the efficacy and safety of pegozafermin.

The co-primary endpoints measured at week 52 are a one-point improvement in fibrosis with no worsening of MASH and MASH resolution with no worsening of fibrosis, assessed at week 52. ENLIGHTEN-Cirrhosis, the second of the two Phase 3 trials in the program, is expected to evaluate the efficacy and safety of pegozafermin in MASH patients with compensated cirrhosis (F4). Pegozafermin is a specifically engineered glycoPEGylated analog of fibroblast growth factor 21 (FGF21) being developed for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) and severe hypertriglyceridemia (SHTG).

FGF21 is an endogenous hormone that has broad effects such as regulating energy expenditure, glucose and lipid metabolism. In clinical trials, pegozafermin has demonstrated direct anti-fibrotic and anti-inflammatory effects on the liver, as well as reduced triglyceride levels, improved insulin resistance and glycemic control, and continued to demonstrate a favorable safety and tolerability profile. The FDA granted pegozafermin Breakthrough Therapy designation (BTD) for the treatment of MASH with fibrosis.

Pegozafermin is advancing into the Phase 3 ENLIGHTEN trial program for MASH and is being studied in the Phase 3 ENTRUST trial for SHTG.