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Abstract Details
Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Stage 3 Fibrosis (FALCON 1): A Randomized Phase 2b Study
1Department of Medicine, University of California San Diego, San Diego, California.
2Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.
3Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan.
4Department of Internal Medicine, Saint Louis University, St Louis, Missouri.
5Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia.
6Pinnacle Clinical Research, San Antonio, Texas.
7Texas Liver Institute, University of Texas at San Antonio, San Antonio, Texas.
8Pinnacle Clinical Research, Austin, Texas.
9Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
10Department of Gastroenterology, Nara Medical University, Nara, Japan.
11Bristol Myers Squibb, Princeton, New Jersey.
12Bristol Myers Squibb, Princeton, New Jersey. Electronic address: edgar.charles@bms.com.
13Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Abstract
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.