TY - JOUR
T1 - Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Stage 3 Fibrosis (FALCON 1)
T2 - A Randomized Phase 2b Study
AU - Loomba, Rohit
AU - Sanyal, Arun J.
AU - Nakajima, Atsushi
AU - Neuschwander-Tetri, Brent A.
AU - Goodman, Zachary D.
AU - Harrison, Stephen A.
AU - Lawitz, Eric J.
AU - Gunn, Nadege
AU - Imajo, Kento
AU - Ravendhran, Natarajan
AU - Akahane, Takemi
AU - Boone, Bradly
AU - Yamaguchi, Masayuki
AU - Chatterjee, Arkendu
AU - Tirucherai, Giridhar S.
AU - Shevell, Diane E.
AU - Du, Shuyan
AU - Charles, Edgar D.
AU - Abdelmalek, Manal F.
N1 - Publisher Copyright:
© 2024 AGA Institute
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
KW - Bridging Fibrosis
KW - FGF21
KW - NASH
UR - http://www.scopus.com/inward/record.url?scp=85164532953&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85164532953&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2023.04.011
DO - 10.1016/j.cgh.2023.04.011
M3 - Article
C2 - 37088457
AN - SCOPUS:85164532953
SN - 1542-3565
VL - 22
SP - 102-112.e9
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 1
ER -