Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Stage 3 Fibrosis (FALCON 1): A Randomized Phase 2b Study.

Autor:	Loomba R; Department of Medicine, University of California San Diego, San Diego, California., Sanyal AJ; Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia., Nakajima A; Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan., Neuschwander-Tetri BA; Department of Internal Medicine, Saint Louis University, St Louis, Missouri., Goodman ZD; Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia., Harrison SA; Pinnacle Clinical Research, San Antonio, Texas., Lawitz EJ; Texas Liver Institute, University of Texas at San Antonio, San Antonio, Texas., Gunn N; Pinnacle Clinical Research, Austin, Texas., Imajo K; Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan., Ravendhran N; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland., Akahane T; Department of Gastroenterology, Nara Medical University, Nara, Japan., Boone B; Bristol Myers Squibb, Princeton, New Jersey., Yamaguchi M; Bristol Myers Squibb, Princeton, New Jersey., Chatterjee A; Bristol Myers Squibb, Princeton, New Jersey., Tirucherai GS; Bristol Myers Squibb, Princeton, New Jersey., Shevell DE; Bristol Myers Squibb, Princeton, New Jersey., Du S; Bristol Myers Squibb, Princeton, New Jersey., Charles ED; Bristol Myers Squibb, Princeton, New Jersey. Electronic address: edgar.charles@bms.com., Abdelmalek MF; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Jazyk:	angličtina
Zdroj:	Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association [Clin Gastroenterol Hepatol] 2024 Jan; Vol. 22 (1), pp. 102-112.e9. Date of Electronic Publication: 2023 Apr 23.
DOI:	10.1016/j.cgh.2023.04.011
Abstrakt:	Background & Aims: Pegbelfermin is a polyethlene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) and stage 3 (bridging) fibrosis. Methods: The FALCON 1 study (NCT03486899) was a multicenter, randomized (1:1:1:1), double-blind, placebo-controlled study. Patients with biopsy-confirmed NASH and stage 3 fibrosis (N = 197) received weekly subcutaneous pegbelfermin (10, 20, or 40 mg) or placebo injections for 48 weeks. The week 24 primary endpoint was a ≥1-point decrease in fibrosis score without NASH worsening or NASH improvement without fibrosis worsening; pegbelfermin dose response was assessed using a Cochran-Armitage trend test across proportions (1-sided α = 0.05). Secondary/exploratory endpoints included histological and noninvasive measures of steatosis, fibrosis, and liver injury/inflammation. Results: At week 24, the primary endpoint was met by 14% (placebo) vs 24%-31% (pegbelfermin arms); statistical significance was not reached due to lack of pegbelfermin dose response (P = .134). At weeks 24 and 48, more patients who received pegbelfermin had ≥30% relative reductions in hepatic fat fraction (magnetic resonance imaging-proton density fat fraction) vs placebo, although no differences reached statistical significance. In the pegbelfermin arms, improvements in liver fibrosis (magnetic resonance elastography and N-terminal type III collagen propeptide) and liver injury/inflammation (alanine aminotransferase, aspartate aminotransferase) were observed vs placebo. Adverse events occurred at similar frequencies across arms. No treatment-related serious adverse events were observed. Conclusions: The FALCON 1 study did not meet its primary endpoint; a ≥1-point decrease in fibrosis score without NASH worsening or NASH improvement without fibrosis worsening assessed via biopsy. Pegbelfermin was generally well tolerated during 48 weeks of treatment. (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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