The U.S. Food and Drug Administration (FDA) has given Efruxifermin (EFX) a breakthrough therapy designation.
EFX is a ground-breaking medication for the treatment of nonalcoholic steatohepatitis (NASH), a serious form of NAFLD (non-alcoholic fatty liver disease).
NASH is characterized by an abnormal buildup of fat in the liver, which damages and stresses liver cells, causing inflammation and fibrosis, which can develop into cirrhosis, liver failure, cancer, and ultimately death.
Akero's lead product candidate for NASH, Efruxifermin (EFX), formerly known as AKR-001, is now being assessed in the ongoing Phase 2b HARMONY trial. EFX is intended to reverse fibrosis, lessen liver fat and inflammation, improve lipoproteins, and raise insulin sensitivity.
Currently, NASH has no approved treatments. About 17 million Americans are thought to be affected by this severe form of liver disease.
When preliminary clinical data suggest a drug may significantly outperform currently available treatments on one or more clinically significant endpoints, the FDA may designate the treatment as a "breakthrough therapy" in order to expedite the development and review of therapies for serious or life-threatening diseases or conditions.
Topline data from HARMONY, a Phase 2b study of EFX in patients with biopsy-confirmed pre-cirrhotic NASH and stage 2 or 3 fibrosis, which was published in September, served as the basis for the designation (F2-F3). Both the study's primary and secondary histology objectives, which were selected to match endpoints permitted by the FDA for registrational trials, were successfully achieved.
To mimic the biological activity profile of FGF21, a hormone that lessens cellular stress and improves metabolic regulation, EFX is designed to mimic its biological activity. In HARMONY, Akero discovered that both the 50 mg and 28 mg doses of EFX had at least a one-stage improvement in liver fibrosis by week 24 (41% and 39%, respectively), compared to 20% for the placebo, with no worsening of NASH.
In addition to achieving this primary endpoint, the study also fulfilled two crucial secondary endpoints, with 76% and 47% of patients treated with 50 mg and 28 mg, respectively, experiencing NASH remission without worsening of fibrosis, as opposed to 15% with the placebo. Additionally, compared to 5% of patients receiving a placebo, 41% and 29% of patients receiving 50 mg and 29% of patients receiving 28 mg saw at least a one-stage improvement in fibrosis and NASH resolution.
A second Phase 2b study, known as SYMMETRY, was launched in July 2021 to assess the efficacy of EFX in patients with compensated cirrhosis (F4) brought on by NASH, a Child-Pugh class A disease. Akero intends to publish the findings from the current SYMMETRY study in the second half of 2023. Results from a 12-week expansion cohort of the SYMMETRY study, which investigates the use of EFX in conjunction with GLP-1 therapy in patients with F1-F3 fibrosis, are due in the first half of 2023.