Jörn Schattenberg, MD, is a professor of medicine and director of the Metabolic Liver Research Program at the University Medical Center Mainz in Germany.

Jörn Schattenberg, MD

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)

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.

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.

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

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Pegozafermin, an FGF21 analog, shows promise in preventing cirrhosis progression in patients with metabolic dysfunction-associated steatohepatitis (MASH), as indicated by a posthoc analysis of the phase 2b ENLIVEN trial. The study, presented at The Liver Meeting 2024, revealed that pegozafermin significantly reduced the progression to cirrhosis in patients with F3 fibrosis. The drug demonstrated histological improvements and favorable anti-inflammatory responses, with no significant adverse events leading to discontinuation. Pegozafermin has received Breakthrough Therapy Designation from the FDA for MASH with fibrosis.

Schattenberg reviews results from a posthoc analysis of the ENLIVEN study suggesting pegozafermin’s impact on preventing progression to cirrhosis. 

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 

, according to findings from a posthoc analysis of the phase 2b ENLIVEN trial.

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.

, 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.

Pegozafermin, an FGF21 analog, shows promise in preventing cirrhosis progression in patients with metabolic dysfunction-associated steatohepatitis (MASH), as demonstrated in a posthoc analysis of the phase 2b ENLIVEN trial. The study, presented at The Liver Meeting 2024, highlighted pegozafermin's ability to improve liver histology and non-invasive fibrosis markers. The US FDA granted it Breakthrough Therapy Designation for MASH with fibrosis. Pegozafermin's potential to enhance patients' quality of life by preventing cirrhosis progression underscores its clinical significance.

Schattenberg explains pegozafermin’s mechanism of action and describes the importance of preventing progression to cirrhotic MASH.

Jörn Schattenberg, MD

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