Survodutide upholds ‘promising’ reduced liver fat, fibrosis biomarkers in MASH at 28 weeks
Click Here to Manage Email Alerts
Key takeaways:
- Survodutide substantially reduced liver fat content, transaminases and fibrosis markers in metabolic dysfunction-associated steatohepatitis.
- Survodutide was generally well-tolerated in a 28-week interim analysis.
WASHINGTON — Survodutide sustained improvement in liver fat content, liver enzymes and fibrosis biomarkers in patients with metabolic dysfunction-associated steatohepatitis at 28 weeks, according to a late-breaking abstract presented here.
“GLP-1 agonists have demonstrated promising efficacy in patients with MASH, but their effects are mediated by weight loss with no direct effects on the liver,” Naim Alkhouri, MD, FAASLD, chief medical officer, chief of transplant hepatology and director of the fatty liver program at Arizona Liver Health, told Healio. “Survodutide is a dual GLP-1/glucagon agonist that may affect the liver through multiple direct and indirect mechanisms, providing rationale for studying its effects in patients with at-risk MASH.”
Although topline data were reported earlier this year, in which survodutide (Boehringer Ingelheim, Zealand Pharma) achieved “statistically significant improvement” for MASH and liver fibrosis in 83% of patients at 48 weeks, this study presented at Digestive Disease Week reported on efficacy and safety results from a preplanned interim analysis after 28 weeks.
“In an interim analysis of the trial at 28 weeks, survodutide was associated with significant improvement in liver fat content as measured by MRI-PDFF, significant improvement in liver enzymes and improvement in fibrosis biomarkers,” Alkhouri told Healio. “Patients had significant weight loss and improvement in HbA1C.”
Among 138 patients with MASH (mean age, 51.7 years; 55% women; mean BMI, 35.6 kg/m2) who were randomly assigned once-weekly subcutaneous injections of 2.4 mg, 4.8 mg or 6 mg of survodutide or placebo, there was significant change from baseline in liver fat content: –55.4% (2.4 mg), –65.3% (4.8 mg), –62% (6 mg) and –13.1% (placebo).
The researchers reported a mean absolute reduction in alanine aminotransferase of –37.8 U/L for all survodutide doses (baseline: 57.2 U/L) compared with –10.4 U/L for placebo (baseline: 65 U/L), as well as a mean absolute reduction in aspartate aminotransferase of –30.8 U/L (baseline: 47.6 U/L) for survodutide vs. –5.1 U/L (baseline: 54.5 U/L) for placebo.
Alkhouri and colleagues also noted that patients who received survodutide achieved a mean relative reduction of type III collagen propeptide (–22.6%; baseline: 48.1 ng/mL) compared with placebo (1.6%; baseline: 44.61 ng/ml). Likewise, the mean absolute reduction of enhanced liver fibrosis score was greater for survodutide (–0.64; baseline: 9.7) vs. placebo (–0.10; baseline: 9.5).
The researchers reported occurrence of any adverse events in 92.3% of patients across all survodutide groups vs. 88.2% in the placebo group. Gastrointestinal adverse events that prompted discontinuation of treatment occurred in 18.3% of patients who received survodutide and 2.8% of patients who received placebo; however, no unexpected safety issues were noted.
“Survodutide may have additional benefits on top of traditional GLP-1 agonists in terms of direct effects on the liver and potential improvement in liver fibrosis,” Alkhouri said. “[This] is a promising new therapeutic agent that may lead to significant improvement in MASH activity, fibrosis and extrahepatic manifestations of MASH.”
Collapse
Alkhouri N, et al. Survodutide reduces liver fat content, transaminases and fibrosis markers with good safety profile in people with metabolic dysfunction-associated steatohepatitis (MASH): An interim analysis of a randomized, double-blind, placebo-controlled phase 2 trial. Presented at: Digestive Disease Week; May 18-21, 2024; Washington (hybrid).
Click Here to Manage Email Alerts