Pegozafermin, a potential treatment for improving fibrosis in NASH patients: Phase 2b Trial

Written By : Dr. Kamal Kant Kohli Published On 2023-07-05T20:00:12+05:30 | Updated On 5 July 2023 8:00 PM IST

USA: The positive outcomes of a phase 2b trial support the further advancement of pegozafermin into phase 3 trials for NASH treatment. If successful, pegozafermin could provide a much-needed therapeutic option for patients with NASH and potentially improve their long-term liver health.

The phase 2b clinical trial presented at the European Association for the Study of the Liver (EASL) Congress 2023 has demonstrated promising results for pegozafermin as a potential treatment for nonalcoholic steatohepatitis (NASH) patients with fibrosis.

The trial, simultaneously published in The New England Journal of Medicine, showed that more than 1-in-4 patients receiving 30 mg and 44 mg doses of pegozafermin met the criteria for fibrosis improvement, compared to only 7% in the placebo group. The parent company, 89 bio, has expressed plans to discuss the advancement of pegozafermin into phase 3 trials for NASH with regulatory agencies in the second half of 2023.

Led by Dr. Rohit Loomba, Chief of the Division of Gastroenterology and Hepatology at the University of California San Diego School of Medicine, the trial demonstrated consistent positive results regarding efficacy, safety, tolerability, and dosing convenience. Pegozafermin, a long-acting glycopegylated fibroblast growth factor 21 (FGF21) analogue, is being developed to treat both NASH and hypertriglyceridemia.

The phase 2b ENLIVEN trial enrolled a population of patients aged 21-75 years with biopsy-confirmed NASH and stage F2 or F3 fibrosis. It was a randomized, double-blind, 24-week trial that involved the administration of subcutaneous pegozafermin at various doses or a placebo on a weekly or biweekly basis. A total of 222 patients participated in the trial, with 219 receiving at least one dose of pegozafermin or placebo therapy.

● The primary outcomes of interest were fibrosis improvement with no worsening of NASH at 24 weeks and NASH resolution without worsening of fibrosis at 24 weeks.

● Fibrosis improvement was defined as a reduction of at least one stage.

● The results showed that the proportion of patients achieving fibrosis improvement was significantly higher in the pegozafermin groups compared to the placebo group.

● Specifically, 26% of patients in the 30 mg pegozafermin group and 27% in the 44 mg pegozafermin group met the criteria for fibrosis improvement, compared to 7% in the placebo group.

● NASH resolution was also observed in a higher percentage of patients receiving pegozafermin compared to placebo.

The safety analysis revealed that adverse events occurred among more patients receiving pegozafermin than placebo. However, most adverse events were mild, and the incidence of serious adverse events was similar between the pegozafermin and placebo groups.

The promising results of this trial suggest that pegozafermin may be a potential mainstay treatment for NASH, addressing both liver pathology and the underlying metabolic overload associated with the disease. Dr. Arun J. Sanyal, interim-chair of the Division of Gastroenterology, Hepatology and Nutrition at Virginia Commonwealth University, highlighted the efficacy of FGF21 analogs and the potential benefits of pegozafermin for patients already on GLP-1 therapies.

Reference: Loomba R, Sanyal AJ, Kowdley KV, et al. Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH [published online ahead of print, 2023 Jun 24]. N Engl J Med. 2023;10.1056/NEJMoa2304286. doi:10.1056/NEJMoa2304286

The New England Journal of MedicinePegozaferminnonalcoholic steatohepatitisFibrosis

Source : The New England Journal of Medicine

Dr. Kamal Kant Kohli

Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751