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Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis.

Publication ,  Journal Article
Harrison, SA; Neff, G; Guy, CD; Bashir, MR; Paredes, AH; Frias, JP; Younes, Z; Trotter, JF; Gunn, NT; Moussa, SE; Kohli, A; Nelson, K ...
Published in: Gastroenterology
January 2021

BACKGROUND & AIMS: Aldafermin, an engineered analog of fibroblast growth factor 19, inhibits bile acid synthesis and regulates metabolic homeostasis. We report results from a 24-week, phase 2 study, with serial liver biopsies, of patients with nonalcoholic steatohepatitis (NASH). METHODS: We performed a double-blind study of 78 patients with NASH at 9 centers in the United States. Key inclusion criteria were biopsy-proven NASH with Nonalcoholic Fatty Liver Disease Activity Score ≥4, stage 2 or 3 fibrosis by NASH Clinical Research Network classification, and absolute liver fat content ≥8%, measured by magnetic resonance imaging-proton density fat fraction. Patients were randomly assigned (1:2) to groups given subcutaneous placebo (n = 25) or aldafermin 1 mg (n = 53) daily for 24 weeks. The primary outcome was change in absolute liver fat content from baseline at week 24. Secondary outcomes included serum markers and histologic measures of fibrosis improvement and NASH resolution. RESULTS: At week 24, the aldafermin group had a significant reduction in absolute liver fat content (reduction of 7.7%) compared with placebo (reduction of 2.7%; difference, reduction of 5.0%; 95% confidence interval, reduction of 8.0%-1.9%; P = .002). Aldafermin produced significantly greater decreases in levels of 7α-hydroxy-4-cholesten-3-one, bile acids, alanine and aspartate aminotransferases, and neoepitope-specific N-terminal pro-peptide of type III collagen (Pro-C3) than placebo. Fibrosis improvement (≥1 stage) with no worsening of NASH was achieved in 38% of patients receiving aldafermin vs 18% of patients receiving placebo (P = .10). NASH resolution with no worsening of fibrosis was observed in 24% of patients given aldafermin vs 9% of patients given placebo (P = .20). Discontinuations due to adverse events occurred in no patients in the aldafermin group and 4% of patients in the placebo group. CONCLUSIONS: In a phase 2 trial of patients with NASH, aldafermin reduced liver fat and produced a trend toward fibrosis improvement. ClinicalTrials.gov, Number: NCT02443116.

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Published In

Gastroenterology

DOI

EISSN

1528-0012

Publication Date

January 2021

Volume

160

Issue

1

Start / End Page

219 / 231.e1

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Liver Cirrhosis
  • Humans
  • Gastroenterology & Hepatology
  • Fibroblast Growth Factors
  • Female
  • Double-Blind Method
 

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Harrison, S. A., Neff, G., Guy, C. D., Bashir, M. R., Paredes, A. H., Frias, J. P., … Lieu, H. D. (2021). Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis. Gastroenterology, 160(1), 219-231.e1. https://doi.org/10.1053/j.gastro.2020.08.004
Harrison, Stephen A., Guy Neff, Cynthia D. Guy, Mustafa R. Bashir, Angelo H. Paredes, Juan P. Frias, Ziad Younes, et al. “Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis.Gastroenterology 160, no. 1 (January 2021): 219-231.e1. https://doi.org/10.1053/j.gastro.2020.08.004.
Harrison SA, Neff G, Guy CD, Bashir MR, Paredes AH, Frias JP, et al. Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis. Gastroenterology. 2021 Jan;160(1):219-231.e1.
Harrison, Stephen A., et al. “Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis.Gastroenterology, vol. 160, no. 1, Jan. 2021, pp. 219-231.e1. Pubmed, doi:10.1053/j.gastro.2020.08.004.
Harrison SA, Neff G, Guy CD, Bashir MR, Paredes AH, Frias JP, Younes Z, Trotter JF, Gunn NT, Moussa SE, Kohli A, Nelson K, Gottwald M, Chang WCG, Yan AZ, DePaoli AM, Ling L, Lieu HD. Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis. Gastroenterology. 2021 Jan;160(1):219-231.e1.
Journal cover image

Published In

Gastroenterology

DOI

EISSN

1528-0012

Publication Date

January 2021

Volume

160

Issue

1

Start / End Page

219 / 231.e1

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Liver Cirrhosis
  • Humans
  • Gastroenterology & Hepatology
  • Fibroblast Growth Factors
  • Female
  • Double-Blind Method