Liver and Bile

N Engl J Med. 2023;389(11):998–1008

Loomba R, Sanyal AJ, Kowdley KV, Bhatt DL, Alkhouri N, Frias JP, Bedossa P, Harrison SA, Lazas D, Barish R, Gottwald MD, Feng S, Agollah GD, Hartsfield CL, Mansbach H, Margalit M, Abdelmalek MF

Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH

Background: Pegozafermin is a long-acting glycopegylated (pegylated with the use of site-specific glycosyltransferases) fibroblast growth factor 21 (FGF21) analogue in development for the treatment of non-alcoholic steatohepatitis (NASH) and severe hypertriglyceridemia. The efficacy and safety of pegozafermin in patients with biopsy-proven non-cirrhotic NASH are not well established.
Methods: In this phase 2b, multicenter, double-blind, 24-week, randomized, placebo-controlled trial, the authors randomly assigned patients with biopsy-confirmed NASH and stage F2 or F3 (moderate or severe) fibrosis to receive subcutaneous pegozafermin at a dose of 15 mg or 30 mg weekly or 44 mg once every 2 weeks or placebo weekly or every 2 weeks. The 2 primary end points were an improvement in fibrosis (defined as reduction by ≥ 1 stage, on a scale from 0 to 4, with higher stages indicating greater severity), with no worsening of NASH at 24 weeks and NASH resolution without worsening of fibrosis at 24 weeks. Safety was also assessed.
Results: Among the 222 patients who underwent randomization, 219 received pegozafermin or placebo. The percentage of patients who met the criteria for fibrosis improvement was 7% in the pooled placebo group, 22% in the 15-mg pegozafermin group (difference vs. placebo, 14 percentage points; 95% confidence interval [CI]: -9–38), 26% in the 30-mg pegozafermin group (difference, 19 percentage points; 95% CI: 5–32; p = 0.009), and 27% in the 44-mg pegozafermin group (difference, 20 percentage points; 95% CI: 5–35; p = 0.008). The percentage of patients who met the criteria for NASH resolution was 2% in the placebo group, 37% in the 15-mg pegozafermin group (difference vs. placebo, 35 percentage points; 95% CI: 10–59), 23% in the 30-mg pegozafermin group (difference, 21 percentage points; 95% CI: 9–33), and 26% in the 44-mg pegozafermin group (difference, 24 percentage points; 95% CI: 10–37). The most common adverse events associated with pegozafermin therapy were nausea and diarrhea.

Conclusions: In this phase 2b trial, treatment with pegozafermin led to improvements in fibrosis. These results support the advancement of pegozafermin into phase 3 development.

R. Loomba, M.D., Professor of Medicine, NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA, E-Mail: roloomba@health.ucsd.edu

DOI: 10.1056/nejmoa2304286

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Liver and Bile

Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: A multicohort study

Lancet. 2023;402(10406):988–96

Serra-Burriel M, Juanola A, Serra-Burriel F, Thiele M, Graupera I, Pose E, Pera G, Grgurevic I, Caballeria L, Piano S, van Kleef L, Reichert M, Roulot D, Pericàs JM, Schattenberg JM, Tsochatztis EA, Guha IN, Garcia-Retortillo M, Hernández R, Hoyo J, Fuentes M, Expósito C, Martínez A, Such P, Madir A, Detlefsen S, Tonon M, Martini A, Ma AT, Pich J, Bonfill E, Juan M, Soria A, Carol M, Gratacós-Ginès J, Morillas RM, Toran P, Navarrete JM, Torrejón A, Fournier C, Llorca A, Arslanow A, de Koning HJ, Cucchietti F, Manns M, Newsome PN, Hernáez R, Allen A, Angeli P, de Knegt RJ, Karlsen TH, Galle P, Wong VWS, Fabrellas N, Castera L, Krag A, Lammert F, Kamath PS, Ginès P; LiverScreen Consortium Investigators

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Liver and Bile

Risk of severe infection in patients with biopsy-proven non-alcoholic fatty liver disease – A population-based cohort study

Clin Gastroenterol Hepatol. 2023;21(13):3346–55.e19