Akero Therapeutics, Inc. (NASDAQ: AKRO) has just released preliminary topline week 96 results from the Phase 2b Symmetry study, which evaluated the efficacy and safety of its lead product candidate, efruxifermin (EFX), in patients with biopsy-confirmed compensated cirrhosis (F4), Child-Pugh class A, due to metabolic dysfunction-associated steatohepatitis (MASH).
In the primary analysis of patients with baseline and week 96 biopsies, 39% of patients treated with 50mg EFX experienced reversal of cirrhosis with no worsening of MASH, compared to 15% for placebo. In the intent-to-treat (ITT) population, 29% of patients in the 50mg EFX group experienced reversal of cirrhosis with no worsening of MASH, compared to approximately 12% in the placebo group.
Notably, there was a doubling of the effect size from weeks 36 to 96 in the 50mg group, highlighting the benefit of longer EFX treatment for patients with compensated cirrhosis (F4). In a subgroup of patients not taking GLP-1 at baseline, 45% in the 50mg EFX group experienced reversal of cirrhosis with no worsening of MASH compared to 17% for placebo, indicating that the observed reversal of cirrhosis was not attributable to GLP-1 therapy.
The reversal of cirrhosis was supported by improvements in noninvasive measures of liver fibrosis and injury. Specifically, the EFX groups showed significant improvements in the ELF score, liver stiffness (measured by FibroScan), ALT, and AST compared to the placebo group.
EFX was reported to be generally well-tolerated, with no deaths on EFX and only one death in the placebo arm.
These results have been described as setting EFX apart from other approved or investigational treatments in the MASH landscape, with transformational potential. The company looks forward to continuing the evaluation of 50mg EFX in its ongoing Phase 3 Synchrony Outcomes study in patients with compensated cirrhosis due to MASH.
Cirrhosis due to MASH is a life-threatening disease with a high risk of liver failure, cancer, and eventual death, and by 2030, an estimated 3 million Americans are projected to have MASH cirrhosis.
The Phase 2b Symmetry study is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial in adult patients with biopsy-confirmed compensated cirrhosis (F4, Child-Pugh A) due to MASH. It enrolled a total of 182 patients, randomized to receive once-weekly subcutaneous dosing of 28mg or 50mg EFX, or placebo for 36 weeks.
EFX, Akero’s lead product candidate for MASH, is currently being evaluated in three ongoing Phase 3 studies. In multiple Phase 2 studies, EFX has been observed to reverse fibrosis, resolve MASH, reduce non-invasive markers of fibrosis and liver injury, and improve insulin sensitivity and lipoprotein profile.
Following these announcements, the company's shares moved 103.0%, and are now trading at a price of $53.14. Check out the company's full 8-K submission here.
