Jörn Schattenberg, MD: Pegozafermin and Preventing Progression to Cirrhosis in MASH

Pegozafermin, an FGF21 analog, may play an important role in preventing progression to cirrhosis in patients with metabolic dysfunction-associated steatohepatitis (MASH), according to findings from a posthoc analysis of the phase 2b ENLIVEN trial.

The research was presented at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) in San Diego, California, by Jörn Schattenberg, MD, a professor of medicine and director of the Metabolic Liver Research Program at the University Medical Center Mainz in Germany.

Pegozafermin was granted Breakthrough Therapy Designation for MASH with fibrosis by the US Food and Drug Administration on September 21, 2023, based on data from the ENLIVEN trial demonstrating both the 44 mg every 2 weeks and 30 mg weekly doses met the primary histology endpoints and also had statistically significant and clinically meaningful improvements in liver fat, non-invasive markers of liver fibrosis and inflammation, and meaningful improvements in other metabolic and lipid markers.

In an interview with HCPLive, Schattenberg highlighted FGF21 as a "metabolic master regulator," describing its influence on multiple organs and tissues to correct metabolic imbalances. As an FGF21 analog, he noted pegozafermin’s potential to prevent progression to cirrhosis in patients with MASH.

The posthoc findings he presented at AASLD showed treatment with pegozafermin led to a reduction in the proportion of patients with baseline F3 fibrosis who progressed to cirrhosis. Of note, relative to F3 progressors on placebo, progressors receiving pegozafermin demonstrated improvement in histological disease activity and liver-related noninvasive tests, suggesting pegozafermin may have clinical benefits in patients with histological fibrosis progression.

“I see these patients with cirrhosis in my clinic every day. I see them in end-stage, with ascites, bleeding, varices, cancer, and that's really something that we could have prevented, because the disease is slowly progressive,” Schattenberg explained.

Beyond preventing these complications, he also cited the importance of preventing progression to cirrhosis for preserving patients’ quality of life and their ability to function on a daily basis.

Editors’ note: Schattenberg has relevant disclosures with Boehringer Ingelheim, Gilead Sciences, Intercept, Ipsen, Inventiva Pharma, Madrigal Pharmaceuticals, Novartis, Novo Nordisk, Pfizer, Sanofi, Astra Zeneca, 89Bio, and others.

References

1. ^{Schattenberg J, Hartsfield C, Sanyal A, et al. Pegozafermin reduced progression to cirrhosis: A post-hoc analysis from the Phase 2b ENLIVEN study. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.}
2. ^{Brooks A. Pegozafermin Enters Phase 3 Clinical Trial Program for MASH, Fibrosis. HCPLive. March 12, 2024. https://www.hcplive.com/view/pegozafermin-enters-phase-3-clinical-trial-program-mash-fibrosis}