A randomized, double-blind, placebo-controlled trial of aldafermin in patients with NASH and compensated cirrhosis

Mary E. Rinella, Hsiao D. Lieu, Kris V. Kowdley, Zachary D. Goodman, Naim Alkhouri, Eric Lawitz, Vlad Ratziu, Manal F. Abdelmalek, Vincent Wai Sun Wong, Ziad H. Younes, Aasim M. Sheikh, Donald Brannan, Bradley Freilich, Fernando Membreno, Marie Sinclair, Liza Melchor-Khan, Arun J. Sanyal, Lei Ling, Stephen A. Harrison

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background and Aims: Aldafermin, an engineered analog of the human hormone FGF19, improves liver histology in patients with noncirrhotic NASH; however, its efficacy and safety in compensated cirrhosis is unknown. No drug has yet to demonstrate benefit in the compensated NASH population. Approach and Results: In this multicenter, double-blind, placebo-controlled, phase 2b trial, 160 patients with compensated NASH cirrhosis were randomized to aldafermin 0.3 mg (n = 7), 1 mg (n = 42), 3 mg (n = 55), or placebo (n = 56) for 48 weeks. The 0.3 mg group was discontinued to limit exposure to suboptimal doses. The primary end point was a change in Enhanced Liver Fibrosis from baseline to week 48. The analyses were performed in the intention-To-Treat population. At week 48, the least-squares mean difference in the change in Enhanced Liver Fibrosis was-0.5 (95% CI,-0.7 to-0.2; p = 0.0003) between the 3 mg group and the placebo group. 15%, 21%, and 23% of patients in the placebo, 1 mg, and 3 mg group, respectively, achieved fibrosis improvement ≥ 1 stage; and 13%, 16%, and 20% achieved fibrosis improvement ≥ 1 stage without NASH worsening. Improvement in alanine aminotransferase, aspartate aminotransferase, neoepitope-specific N-Terminal pro-peptide of type III collagen, and liver stiffness favored aldefermin groups over placebo. Diarrhea was the most frequent adverse event, occurring at 26% and 40% in the 1 mg and 3 mg groups, respectively, compared to 18% in the placebo group. Overall, 0%, 2%, and 9% of patients in the placebo, 1 mg, and 3 mg group, respectively, discontinued due to treatment-related adverse events. Conclusions: Aldafermin 3 mg resulted in a significant reduction in Enhanced Liver Fibrosis in patients with compensated NASH cirrhosis.

Original languageEnglish (US)
Pages (from-to)674-689
Number of pages16
JournalHepatology
Volume79
Issue number3
DOIs
StatePublished - Mar 2024

ASJC Scopus subject areas

  • Hepatology

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