Akero Therapeutics Begins Phase 3 SYNCHRONY Trial of Efruxifermin for MASH-Related Compensated Cirrhosis

On June 11, 2024, Akero Therapeutics, Inc. (Nasdaq: AKRO), a clinical-stage company focusing on groundbreaking treatments for serious metabolic diseases, announced the commencement of the SYNCHRONY Outcomes study. This Phase 3 clinical trial aims to assess the efficacy and safety of efruxifermin (EFX) in patients suffering from compensated cirrhosis (fibrosis stage 4) due to metabolic dysfunction-associated steatohepatitis (MASH).

Chief Development Officer Kitty Yale emphasized the dire needs of patients with compensated cirrhosis, citing the heightened risks of liver failure, hepatocellular carcinoma, and mortality. Encouraging results from the Phase 2b SYMMETRY study in similar patients have led to the belief that EFX could potentially become one of the first approved treatments for both pre-cirrhotic and cirrhotic patients.

SYNCHRONY Outcomes is a global, randomized, placebo-controlled Phase 3 trial, actively enrolling patients with compensated cirrhosis (F4) due to MASH. Participants will receive weekly injections of either 50mg of EFX or a placebo. The primary histology endpoint for Cohort 1 will examine fibrosis regression without worsening MASH after 96 weeks of treatment. Following this period, patients will continue with their assigned treatment to evaluate primary outcomes, including all-cause mortality and liver-related clinical outcomes. These outcomes will be measured by the time to the first occurrence of pre-defined, adjudicated events across both study cohorts (Cohorts 1 and 2). Secondary endpoints will track changes in non-invasive markers of liver injury and fibrosis, glycemic control, and lipid levels.

The broader SYNCHRONY program comprises three ongoing trials: SYNCHRONY Histology, SYNCHRONY Real-World, and SYNCHRONY Outcomes. SYNCHRONY Histology and Real-World are investigating EFX's impact on patients with pre-cirrhotic MASH (F2-F3 fibrosis) and those with MASH (F1-F3 fibrosis) or metabolic dysfunction-associated steatotic liver disease (MASLD). SYNCHRONY Outcomes specifically targets patients with compensated cirrhosis due to MASH (F4 fibrosis). In these trials, participants self-administer EFX using the LyoJect 3S dual chamber syringe, which is designed for potential commercial use.

Efruxifermin (EFX) is Akero’s lead candidate for treating MASH. It is a unique Fc-FGF21 fusion protein designed to emulate the biological activity of native FGF21, a hormone that alleviates cellular stress and regulates metabolism. EFX has shown promise in reducing liver fat and inflammation, reversing fibrosis, improving insulin sensitivity, and enhancing lipid profiles. This comprehensive approach addresses the multifaceted nature of MASH, including reducing cardiovascular disease risk factors, which are a leading cause of death among MASH patients. EFX requires only weekly administration and has been well tolerated in clinical trials so far.

MASH, a severe form of MASLD, affects over 17 million Americans. It is characterized by excessive fat accumulation in the liver, leading to cell stress, inflammation, and fibrosis. This can further advance to cirrhosis, liver failure, cancer, and death. MASH is the fastest-growing cause of liver transplants and liver cancer in the US and Europe.

Akero Therapeutics, headquartered in South San Francisco, is dedicated to developing transformative treatments for severe metabolic diseases, particularly MASH. Their lead product, EFX, is under evaluation in the ongoing SYMMETRY study, a 96-week Phase 2b trial for patients with compensated cirrhosis due to MASH (F4 fibrosis), alongside three Phase 3 trials: SYNCHRONY Histology, SYNCHRONY Real-World, and SYNCHRONY Outcomes. These efforts build upon the promising results from the HARMONY and SYMMETRY Phase 2b studies.