Efruxifermin Granted FDA Breakthrough Therapy Designation for NASH

Akero Therapeutics, Inc. a clinical-stage company developing transformational treatments for patients with serious metabolic disease marked by high unmet medical need, announced that efruxifermin (EFX) has received a Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) for the treatment of nonalcoholic steatohepatitis (NASH). There are currently no approved therapies for the treatment of NASH, which is a serious form of liver disease estimated to affect 17 million Americans.

“We are proud to have the FDA recognize the potential therapeutic benefit of EFX through this Breakthrough Therapy Designation,” said Andrew Cheng, M.D., Ph.D., president and chief executive officer of Akero. “With the global prevalence of NASH continuing to rise, we are committed more than ever to developing therapeutics that can treat NASH holistically and reverse fibrosis rapidly. This designation is an important milestone for Akero and the NASH community as we continue to evaluate EFX as a potential foundational monotherapy.”

The FDA’s Breakthrough Therapy Designation is meant to expedite development and review of a therapy for a serious or life-threatening disease or condition when preliminary clinical evidence indicates the drug may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies. The designation is based on topline data released in September from HARMONY, a Phase 2b study of EFX in patients with biopsy-confirmed pre-cirrhotic NASH, fibrosis stage 2 or 3 (F2-F3). The study met its primary and secondary histology endpoints, which were selected to match endpoints accepted by the FDA for registrational trials.

EFX is engineered to mimic the biological activity profile of FGF21, a hormone responsible for alleviating cellular stress and improving metabolic regulation. In HARMONY, Akero observed that both 50mg and 28mg doses of EFX produced at least a one stage improvement in liver fibrosis with no worsening of NASH by week 24 (41% and 39%, respectively) compared with 20% for placebo. In addition to meeting this primary endpoint, the study also met two key secondary endpoints with 76% and 47% of patients treated with 50mg and 28mg, respectively, achieving NASH resolution without worsening of fibrosis, compared with 15% for placebo. Additionally, 41% and 29% of patients treated with 50mg and 28mg, respectively, achieved at least a one-stage improvement in fibrosis and NASH resolution, compared with 5% for placebo.

An additional Phase 2b study, SYMMETRY, was initiated in July of 2021 to assess EFX in patients with compensated cirrhosis (F4) due to NASH, Child-Pugh class A. Akero expects to report results from the ongoing SYMMETRY study in the second half of 2023. Results from a 12-week expansion cohort of the SYMMETRY study, evaluating treatment of EFX in combination with GLP-1 therapy in patients with F1-F3 fibrosis, are expected in the first half of 2023.