Phase 2b HARMONY Study Shows Significant Histological Progress at 96 Weeks for Akero Therapeutics

Akero Therapeutics, a company focused on developing treatments for serious metabolic diseases, particularly metabolic dysfunction-associated steatohepatitis (MASH), has reported positive results from its Phase 2b HARMONY study. The study assessed the efficacy and safety of efruxifermin (EFX), the company's lead product candidate, in patients with pre-cirrhotic MASH and fibrosis stages 2 or 3. The 96-week preliminary topline results showed significant improvements in fibrosis without worsening of MASH for the 50mg and 28mg EFX groups, with response rates increasing to 75% and 46% respectively, compared to 24% for the placebo group.

Moreover, the study achieved its secondary endpoints, with 36% and 31% of patients treated with 50mg and 28mg EFX, respectively, experiencing a two-stage improvement in fibrosis without MASH worsening. This is over ten times the placebo rate of 3%. The results were based on both primary analysis, which included patients with baseline and week 96 biopsies, and intent-to-treat analysis, which included all randomized and dosed patients.

EFX has been well-tolerated, with no reported deaths and most adverse events being transient gastrointestinal issues. The drug has also shown potential in treating patients with more advanced fibrosis, which is crucial as these individuals are at a higher risk of progressing to cirrhosis.

Dr. Stephen Harrison, principal investigator of the HARMONY study, highlighted the significant response rates reported for EFX, which are the largest to date for MASH populations. He expressed optimism about the ongoing Phase 3 SYNCHRONY Histology study and EFX's potential as a MASH medicine.

Andrew Cheng, CEO of Akero, emphasized the importance of the two-stage fibrosis improvement observed in EFX-treated patients and the sustained fibrosis improvement with longer exposure to the drug. Akero is looking forward to continuing the evaluation of EFX in ongoing Phase 3 trials.

The HARMONY study enrolled 128 patients who received weekly subcutaneous dosing of EFX or placebo for 24 weeks. The primary efficacy endpoint was the proportion of subjects achieving at least one-stage fibrosis improvement without MASH worsening at week 24. Secondary measures at week 96 included further fibrosis improvements, changes in liver enzymes, noninvasive markers of liver fibrosis, glycemic control, and body weight, along with safety and tolerability assessments.

EFX, designed to mimic the biological activity of native FGF21, has shown potential in reducing liver fat and inflammation, reversing fibrosis, and improving insulin sensitivity and lipoproteins in clinical trials. It offers the possibility of addressing the multifaceted disease state of MASH and improving cardiovascular risk factors, which are significant in MASH patients.

Akero Therapeutics is a clinical-stage company dedicated to developing transformative treatments for patients with serious metabolic diseases, including MASH, for which there are currently no approved therapies. The company's lead product candidate, EFX, is also being evaluated in two Phase 3 clinical trials: the SYNCHRONY Histology study in patients with pre-cirrhotic MASH and the SYNCHRONY Real-World study in patients with MASH or metabolic-associated steatotic liver disease (MASLD). Akero is headquartered in South San Francisco and is actively advancing its mission to bring innovative treatments to patients in need.