89bio, Inc. announced that data from the Phase 2b ENLIVEN trial evaluating treatment with pegozafermin in patients with nonalcoholic steatohepatitis (NASH) were published online in the New England Journal of Medicine (NEJM). The data were simultaneously presented in a late-breaking oral session at the European Association for the Study of the Liver (EASL) Congress 2023 in Vienna, Austria and were also selected for inclusion in the Best of EASL Congress summary. The randomized, double-blind, placebo-controlled 24-week Phase 2b ENLIVEN trial evaluated 219 adult patients of whom 192 had biopsy-confirmed fibrosis stages F2-F3 NASH and NAS = 4 for 24 weeks.

In this trial, treatment with 44mg every-two-week (second quarterW) and 30mg (QW) dosing groups resulted in statistically significant changes on both primary histology endpoints demonstrating at least one-stage fibrosis improvement without worsening of NASH (27% and 26%, respectively) at 3.5 times the placebo rate (7%) and NASH resolution without worsening of fibrosis (26% and 23%, respectively), between 12 to 14 times the placebo rate (2%). Treatment with pegozafermin also led to clinically meaningful changes compared to baseline in liver fat and other key non-invasive tests (NITs) of liver inflammation and fibrosis. Improvements were observed in HbA1c, adiponectin and across lipid markers that are important factors for an effective treatment for NASH.

In addition, reductions in liver and spleen volume were observed. The trial included 14 biopsy confirmed NASH patients with compensated cirrhosis (F4 patients) who were not part of the primary analysis, but continued in the study, 12 of which underwent a follow-up biopsy at Week 24. Five out of eleven of these patients treated with pegozafermin had fibrosis improvement =1 stage without worsening of NASH.

New results presented at EASL showed: Patients on GLP-1 treatment who received pegozafermin saw broad incremental benefits across liver markers of fibrosis, including the Enhanced Liver Fibrosis (ELF) Test, Vibration-controlled transient elastography and the FibroScan-AST (FAST) score. Improvements were observed in liver fat, ALT levels as well as metabolic (HbA1c) markers. Across all patients, treatment with pegozafermin demonstrated statistically significant improvements on additional NITs for hepatic inflammation and fibrosis, including ELF, FIB-4 index and FAST.

These data were consistent with previously reported markers and further build on the positive impact of pegozafermin on NITs. Treatment with pegozafermin was consistent and showed significant benefit in achieving fibrosis improvement across several key sub populations including type 2 diabetes status, fibrosis stage (F2 or F3), and ALT levels. There were no clinically relevant changes observed on vital signs, bone biomarkers or dual x-ray absorptiometry (DEXA) scans.

Pegozafermin demonstrated a favorable safety and tolerability profile consistent with prior studies. Across dose groups, the most common adverse events (AEs) were Grade 1 or 2 gastrointestinal events (diarrhea, nausea and increased appetite), most of which were mild to moderate in nature. No clinically relevant effects on DEXA scans, bone biomarkers or vital signs were noted.

No drug-induced liver injury, tremor or hypersensitivity reactions were reported.