Akero Therapeutics announced positive preliminary topline results from its Phase 2b SYMMETRY study, revealing that efruxifermin (EFX) demonstrated statistically significant reversal of compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The multicenter, randomized, double-blind, placebo-controlled trial involved adult subjects with biopsy-confirmed compensated cirrhosis. The results mark a potential breakthrough in treating this advanced stage of MASH, where few effective options currently exist.
Among patients with both baseline and week 96 biopsies, 39% of those treated with 50mg EFX experienced reversal of cirrhosis without any worsening of MASH, compared to 15% in the placebo arm (p=0.009). In the Intent to Treat (ITT) population, 29% of subjects receiving the same dosage showed cirrhosis reversal (p=0.031).
The effect size from week 36 to 96 in patients who received the 50mg dose more than doubled, highlighting the benefit of longer treatment duration. In a subgroup of patients not taking glucagon-like peptide 1 (GLP-1) at baseline, 45% in the 50mg EFX group reported cirrhosis reversal, compared to 17% for the placebo group (p=0.009), suggesting the observed reversal of cirrhosis was not attributable to GLP-1 therapy.
Key Study Findings
The SYMMETRY study, a Phase 2b trial, enrolled 182 patients with biopsy-confirmed compensated cirrhosis (F4, Child-Pugh Class A) due to MASH. Participants were randomized to receive once-weekly subcutaneous doses of 28mg or 50mg EFX, or placebo, for 36 weeks. The primary efficacy endpoint was the proportion of patients who achieved at least a one-stage fibrosis improvement without worsening of MASH at week 36. Week 96 secondary measures included ≥1 stage fibrosis improvement and no worsening of MASH, MASH resolution, change from baseline in liver enzymes, noninvasive markers of liver fibrosis, glycemic control, and lipoproteins, as well as safety and tolerability measures.
Mazen Nourredin, M.D., Professor of Medicine and Transplant Hepatologist at Houston Methodist Hospital, and principal investigator for the SYMMETRY study, stated, “Until today, we’ve not had the prospect of an effective treatment for compensated cirrhosis due to MASH, which is associated with high rates of short-term morbidity and mortality. Now we have reason to be optimistic about the future potential of EFX as a much-needed treatment for cirrhosis, if approved.”
Safety and Tolerability
EFX was generally well-tolerated. There were no deaths on EFX, but one death occurred in the placebo arm due to pneumonia. The most frequent adverse events across both EFX groups were grade 1 or 2 gastrointestinal events (diarrhea, nausea, and increased appetite), which were transient in nature.
Ongoing Phase 3 Trials
Akero is currently evaluating EFX in three ongoing Phase 3 studies: SYNCHRONY Histology (pre-cirrhotic MASH), SYNCHRONY Outcomes (compensated cirrhosis due to MASH), and SYNCHRONY Real-World (MASH or MASLD). These trials build upon the results of the HARMONY study (pre-cirrhotic MASH) and the SYMMETRY study (compensated cirrhosis due to MASH).
About Efruxifermin (EFX)
Efruxifermin (EFX) is Akero’s lead product candidate for MASH, engineered to mimic the biological activity profile of native FGF21. It has been observed to reverse fibrosis (including compensated cirrhosis), resolve MASH, reduce non-invasive markers of fibrosis and liver injury, and improve insulin sensitivity and lipoprotein profile. EFX is designed for convenient once-weekly dosing and has been generally well-tolerated in clinical trials to date.
MASH: A Growing Concern
MASH is a serious form of MASLD estimated to affect over 17 million Americans. It is characterized by excessive fat accumulation in the liver, leading to inflammation and fibrosis, which can progress to cirrhosis, liver failure, cancer, and death. MASH is the fastest-growing cause of liver transplants and liver cancer in the US and Europe. By 2030, an estimated 3 million Americans are projected to have MASH cirrhosis.
