Jörn Schattenberg, MD: Preventing MASH Cirrhosis Progression with Pegozafermin

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

Data from the study were 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 received Breakthrough Therapy Designation for MASH with fibrosis from the US Food and Drug Administration on September 21, 2023. The decision was supported by 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, noninvasive markers of liver fibrosis and inflammation, and meaningful improvements in other metabolic and lipid markers.

In an interview with HCPLive, Schattenberg reviewed key findings from the posthoc analysis, which focused on patients with F3 fibrosis who progressed to cirrhosis within the study’s 24-week duration. Although he noted cirrhosis was not an endpoint that was predefined in the phase 2b ENLIVEN study, this data was still collected in the trial and he indicated it was something he and other investigators were interested in exploring.

In total, 13 of 106 patients with F3 fibrosis at baseline were determined to have progressed to cirrhosis after 24 weeks of treatment. While both placebo and pegozafermin groups experienced some progression, Schattenberg pointed out treatment with pegozafermin led to a reduction in the proportion of patients with baseline F3 fibrosis who progressed to cirrhosis. Additionally, pegozafermin-treated patients demonstrated significant histological improvements and improvement in noninvasive tests, suggesting the drug’s potential clinical benefit in patients with histological fibrosis progression.

“Even in patients who hit cirrhosis, treatment with pegozafermin led to favorable anti-inflammatory responses in these patients… I'm fairly confident that these improvements in NITs will translate into a clinically meaningful benefit,” he said.

Schattenberg also called attention to pegozafermin’s safety and tolerability, even in patients with more advanced disease. He highlighted a lack of side effects or treatment-emergent adverse events that led to treatment discontinuation.

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}