Pegozafermin for Nonalcoholic Steatohepatitis

Pegozafermin is an investigational, long acting glycopegylated fibroblast growth factor 21 (FGF21) analogue which is currently in phase 2 of the drug development phase for the treatment of NASH and phase 3 as a treatment for severe hypertriglyceridemia. The drug has been engineered using a proprietary glycopegylated technology that is designed to increase its overall half-life, allowing the medication to possibly regulate energy expenditure and glucose/lipid metabolism more effectively. The results of this clinical trial may have garnered attention because there are no known treatments for NASH at this time. Pegzafermin has officially been designated as an official breakthrough therapy for NASH by the FDA. (2),(3)

Nonalcoholic steatohepatitis is a severe form of non-alcoholic fatty liver disease (NAFLD) that presents as fibrosis and inflammation of the liver that can progress to more debilitating conditions such as cirrhosis, liver disease and liver cancer. Currently, NAFLD affects approximately 25% of the global population, in which NASH affects around 20% of those NAFLD patients. NASH incidence has increased because of the global obesity epidemic, which is associated with a variety of metabolic comorbidities such as diabetes, hyperlipidemia and systemic hypertension. which increases the risk of cardiovascular disease. (2),(3)

In a multicenter, randomized, double blind, placebo controlled phase 2b trial, pegozafermin was proven to significantly improve NASH without worsening of fibrosis. This study has also shown that this medication is well tolerated and has a favorable safety profile. In addition, the results showed that the drug was effective in multiple subgroups including groups of people who have previously taken GLP-1 therapy. The efficacy of this medication was similar with weekly and every two week dosing intervals, which may allow dosing flexibility for patients who are on an abundance of different medications. The results from this study have provided some promising data as this medication enters the planned phase 3 trials.(1),(4)

References

1) Loomba R., A. J. Sanyal, K. V. Kowdley, D. L. Bhatt, N. Alkhouri, J. P. Frias, P. Bedossa, S. A. Harrison, D. Lazas, R. Barish, M. Gottwald, S. Feng, G. D. Agollah, C. L. Hartsfield, H. Mansbach, M. Margalit, M. F. Abdelmalek. Presented at the EASL International Liver Congress, June 21-24, 2023

2) 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. N Engl J Med. 2023 Sep 14

3) 89bio announces US FDA has granted Breakthrough Therapy designation for pegozafermin in nonalcoholic steatohepatitis (NASH). News release. 89bio, Inc. September 21, 2023. https://www.globenewswire.com/news-release/2023/09/21/2747202/0/en/89bio-Announces-U-S-FDA-has-Granted-Breakthrough-Therapy-Designation-for-Pegozafermin-in-Nonalcoholic-Steatohepatitis-NASH.html (https://www.globenewswire.com/news-release/2023/09/21/2747202/0/en/89bio-Announces-U-S-FDA-has-Granted-Breakthrough-Therapy-Designation-for-Pegozafermin-in-Nonalcoholic-Steatohepatitis-NASH.html)

4) Bhatt, D.L., Bays, H.E., Miller, M. et al. The FGF21 analog Pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial. Nat Med 29, 1782–1792 (2023). https://doi.org/10.1038/s41591-023-02427-z

Nathan Ciepley is a Pharm.D. candidate at Duquesne University’s School of Pharmacy in Pittsburgh who is expected to graduate in spring 2024. He completed this article while on Advanced Pharmacy Practice Rotation at STACK, which focused on specialty pharmacy, technology, and entrepreneurship.