Survodutide meets expectations in MASH

In a phase 2 trial for participants with metabolic dysfunction-associated steatohepatitis (MASH), survodutide met its primary endpoints. The agent reduced liver fat content (LFC), transaminases, and fibrosis markers, while being generally well tolerated.

The multinational, double-blind, phase 2 trial (NCT04771273) involved 295 adults with biopsy-proven MASH, liver fibrosis (stage F1–F3), and a BMI of ≥35 kg/m². Participants were randomised to receive either a placebo or survodutide at doses of 2.4, 4.8, or 6 mg (escalated from 0.3 mg) over 48 weeks. Dr Naim Alkhouri (Arizona Liver Health, AZ, USA) presented the interim analysis results at week 28 [1].

By week 28, 90.9% of participants receiving 2.4 mg, 88.9% receiving 4.8 mg, and 87% receiving 6 mg of survodutide achieved a ≥30% reduction in LFC, compared with 25% of those on placebo (P<0.0001 for all comparisons; see Figure). The mean relative changes in LFC with survodutide were -55.4%, -65.3%, and -62% for the respective doses, compared with -13.1% for placebo. Significant improvements were also observed in liver enzymes: mean absolute reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were -37.8 U/L and -30.8 U/L with survodutide, versus -10.4 U/L and -5.1 U/L with placebo. Pro-peptide of type III collagen (Pro-C3) levels decreased by up to -25.6% with survodutide, compared with an increase of 1.6% with placebo. Enhanced liver fibrosis (ELF) scores decreased by up to 0.8 with survodutide, while there was no change with placebo. Additionally, survodutide also led to significant reductions in body weight (up to 12.5% vs 2.6% with placebo), and haemoglobin A1c (HbA1c) levels (up to 0.8% vs no change with placebo).

Figure: Liver fat content reduction at week 28 [1]



QW, once weekly.

Adverse events (AEs) were reported in 92.3% of the participants receiving survodutide and 88.2% of those receiving placebo, with gastrointestinal issues being the most common in both groups. Gastrointestinal AEs led to discontinuation in 18.3% of the participants receiving survodutide, compared with 2.9% of those receiving placebo. No unexpected safety issues were reported.

“Survodutide significantly reduces LFC, ALT and AST levels, body weight, and HbA1c levels. It also decreases fibrosis biomarkers Pro-C3 and ELF. Discontinuation due to gastrointestinal AEs was dose-dependent, with no unexpected safety trends observed,” concluded Dr Alkhouri.

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   1. 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. 1057a, DDW 2024, 18–21 May, Washington DC, USA.

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Posted on 11 July 202411 July 2024