Efruxifermin with GLP-1RA appears safe, reduces liver fat by 65% in MASH, diabetes
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Key takeaways:
- Efruxifermin with a glucagon-like peptide-1 receptor agonist reduced hepatic fat fraction by 65% in patients with MASH and diabetes.
- Safety and tolerability “were comparable” between treatment and placebo groups.
Efruxifermin with a glucagon-like peptide-1 receptor agonist was well-tolerated and reduced hepatic fat fraction and noninvasive markers of fibrosis among patients with metabolic dysfunction-associated steatohepatitis and type 2 diabetes.
“In 16- to 24-week phase 2 trials of patients with fibrosis stages 1 to 3 (F1-F3) or cirrhosis, efruxifermin improved liver fibrosis and resolved MASH,” Stephen A. Harrison, MD, FAASLD, founder of Pinnacle Clinical Research and Summit Clinical Research and visiting professor of hepatology at the University of Oxford, and colleagues wrote in Clinical Gastroenterology and Hepatology. “Consistent with resolution of histopathology, efruxifermin decreased markers of fibrogenesis and hepatocyte injury concurrently with reductions in liver fat, suggesting in part that it acts directly via mechanisms independent of steatosis reduction.”
They continued: “The direct insulin-sensitizing actions of efruxifermin may complement the pharmacological effects of GLP-1RA, potentially accelerating histopathological improvements in patients with MASH already receiving GLP-1RA.”
In a double-blind, placebo-controlled, phase 2b study, Harrison and colleagues evaluated the safety and efficacy of efruxifermin among 31 adult patients (mean age, 57.4 years; 58% women) with type 2 diabetes and MASH fibrosis on a stable glucagon-like peptide-1 receptor agonist (GLP-1RA) for at least 90 days. Secondary outcomes included changes in hepatic fat fraction, markers of liver injury and fibrosis, and metabolic parameters.
Patients were randomized to subcutaneous efruxifermin 50 mg (n = 21) or placebo (n = 10) once a week for 12 weeks and monitored for an additional 4 weeks. At baseline, most patients were taking once-weekly semaglutide (48%), followed by once-weekly dulaglutide (45.2%) and once-daily liraglutide (7%).
According to results, 94% of patients completed the 12-week study and 4-week follow-up. Safety and tolerability “were comparable” between efruxifermin and placebo groups, with no new adverse events reported. The most frequent treatment-emergent adverse events were mild to moderate nausea (33% vs. 10%, respectively), increased appetite (24% vs. 0%), diarrhea (19% vs. 30%) and decreased appetite (14% vs. 20%).
Further, results showed efruxifermin in combination with a GLP-1RA for 12 weeks reduced hepatic fat fraction by 65% vs. 10% with placebo/GLP-1RA alone, and improved noninvasive markers of liver injury and fibrosis with “significantly greater” reductions from baseline in alanine aminotransferase and aspartate aminotransferase.
“Adding efruxifermin to a background GLP-1RA has an acceptable tolerability profile, supporting further investigation into their potential for co-administration,” Harrison and colleagues wrote. “There are preliminary indications that combining these two mechanistic classes could accelerate resolution of MASH and regression of fibrosis.”
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