89bio, Inc. announced that data from the 48-week extension phase of the Phase 2b ENLIVEN trial evaluating pegozafermin in patients with metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis will be presented in an oral and poster presentation at the European Association for the Study of the Liver (EASL) Congress to be held June 5 to 8, 2024 in Milan, Italy. MASH, also known as nonalcoholic steatohepatitis (NASH), is a chronic and progressive condition that represents a severe form of metabolic dysfunction-associated steatotic liver disease (MASLD). It is characterized by fat accumulation in the liver, which causes inflammation and can ultimately lead to scarring or fibrosis.

By 2030, it is projected to affect over 27 million people in the U.S. The disease is categorized based on the extent of liver fibrosis. In cases of advanced fibrosis, the treatment goal is to improve liver health, reverse fibrosis, and prevent the progression of the disease and related complications such as cirrhosis and cardiovascular risks. Estimates suggest that approximately 20% of patients with MASH may develop cirrhosis, a serious condition that significantly impairs liver function.

Cirrhosis can lead to life-threatening complications from esophageal varices, ascites, or hepatocellular carcinoma. Patients may ultimately require a liver transplant to avoid death from liver failure. ENLIVEN was a multicenter, randomized, double-blind, placebo-controlled Phase 2b trial designed to evaluate the safety and efficacy of weekly or every-two-week dosing of pegozafermin for the treatment of patients with biopsy confirmed MASH and NAS = 4 for 48 weeks.

In the trial, 192 patients were dosed with pegozafermin 15mg QW, 30mg QW and 44mg Q2W, or placebo. Primary outcomes measured were proportion of participants with resolution of MASH without worsening of fibrosis and proportion of participants with =1 stage decrease in fibrosis stage with no worsening of MASH at week 24. Secondary measures included change from baseline in liver fat, liver enzymes, noninvasive markers of liver fibrosis, glycemic control, lipoproteins, and body weight as well as safety and tolerability measures.

Patients who entered the blinded extension phase were subsequently treated for an additional 24 weeks for a total treatment period of 48 weeks. Some patients who were on placebo (n=19) were re-randomized to receive pegozafermin in the extension phase. Key endpoints in the extension phase include liver fat and non-invasive markers of liver fibrosis and inflammation.

ENLIVEN achieved high statistical significance on primary histology endpoints with 30mg QW and 44mg Q2W dosing at week 24. 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. Pegozafermin received Breakthrough Therapy designation (BTD) status from the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) status from the European Medicines Agenda (EMA) for the treatment of MASH with fibrosis. Pegozafermin is being studied in the Phase 3 ENLIGHTEN trial program for MASH and is being studied in the Phase 3 ENTRUST trial for SHTG.