November 08, 2022
2 min read
Harrison SA, et al. Efruxifermin (EFX) in nonalcoholic steatohepatitis with fibrosis: Results from a randomized, double-blind, placebo-controlled, phase 2b trial (HARMONY). Presented at: The Liver Meeting; Nov. 4-8, 2022; Washington (hybrid meeting).
Harrison reports financial relationships with 89 Bio, AgomAB, Akero Therapeutics Inc., Alentis Therapeutics AG, Alimentiv Inc., Altimmune, Arrowhead, Axcella Health Inc., Boston Pharmaceuticals, B Riley FBR Inc., BVF Partners LP, Cohbar Inc., Canfite, Corcept Therapeutics Inc., Chronwell, CiVi, Cymabay Therapeutics Inc., Echosens North America Inc., Enyo Pharma S.A., Fibronostics, Foresite Labs LLC, Fortress Biotech Inc., Galectin Therapeutics Inc., Galmed Research & Dev. LTD, Gilead Sciences, Genfit Corp., GNS, Hepion Pharmaceuticals Inc., Hightide Therapeutics Inc., HistoIndex PTE LTD, Indalo, Inipharm, Intercept Pharmaceuticals Inc., lonis, Kowa Research Institute Inc., Madrigal Pharmaceuticals Inc., Medpace Inc., Metacrine Inc., Microba, NGM Biopharmaceuticals Inc., Northsea Therapeutics B.V., Novartis Pharmaceuticals, Novo Nordisk, Nutrasource, PathAI, Perspectum Diagnostics, Piper Sandler, Poxel, Prometic, Pharma SMT LTD, Ridgeline, Sagimet Biosciences, Sonic Incytes Medical Corp., Terns Inc., Theratechnologies and Viking Therapeutics Inc.
WASHINGTON — Efruxifermin improved liver histology, liver fat content and noninvasive markers of disease in patients with stage 2 or 3 fibrosis related to nonalcoholic steatohepatitis, according to late-breaking data at The Liver Meeting.
In a previous phase 2a study, efruxifermin (EFX), a long-acting FGF21 analog, reduced liver fat content in patients with stage F1 to F3 NASH and improved noninvasive markers of liver inflammation, injury, fibrosis, glucose and lipid metabolism, Stephen A. Harrison, MD, FAASLD, medical director for Pinnacle Clinical Research and president of Summit Clinical Research in San Antonio, told attendees.
To expand on these findings, Harrison and colleagues enrolled 128 patients (62% women; mean age, 55 years) with NASH and F2 or F3 fibrosis in the HARMONY phase 2b study. Patients received once-weekly EFX 28 mg (n = 42), EFX 50 mg (n = 43) or placebo (n = 43) for 96 weeks. Harrison noted approximately 70% of enrolled patients had type 2 diabetes and 66% had stage F3 fibrosis.
Researchers analyzed patients at 24 weeks for fibrosis improvement of at least one stage with no worsening of NASH, as well as the effect of EFX on NASH. Biopsies were collected for 113 participants at week 24 (50 mg, n =34; 28 mg, n =38; placebo, n =41).
According to study results, 41% of patients in the 50 mg group and 39% of patients in the 28 mg group achieved the primary endpoint of fibrosis improvements of at least one stage and no worsening of NASH compared with 20% of patients in the placebo group. Further, a higher proportion of patients in the EFX-treated groups also achieved resolution of NASH with no worsening of fibrosis (76% and 47%, respectively, vs. 15%) as well as the composite endpoints of fibrosis improvement and NASH resolution compared with placebo (41% and 29% vs. 5%).
Of note, patients in the 50 mg and 28 mg groups (15% and 16%, respectively) achieved fibrosis improvement of at least two stages and no worsening of NASH at week 24 compared with 5% in the placebo group.
According to Harrison, EFX also improved liver fact content and serum markers of liver injury, fibrosis, glucose and lipid metabolism. Drug-related adverse events were mild to moderate and included diarrhea and nausea. Five patients discontinued the study because of adverse events.
“Both efruxifermin doses achieved a statistically significant difference from placebo for at least one stage fibrosis improvement and NASH resolution,” Harrison concluded. “Efruxifermin also approved markers of liver injury and non-invasive markers of fibrosis as well as lipoprotein profile and glycemic control.”
He continued, “There was weight loss noted with the high-dose arm and [EFX] was generally well-tolerated with low numbers of treatment discontinuations. These data support initiation of efruxifermin phase 3 programs.”