Akero Therapeutics, Inc. (NASDAQ: AKRO) has released preliminary topline week 96 results from the Harmony, a phase 2b study evaluating the efficacy and safety of its lead product candidate efruxifermin (EFX) in patients with pre-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH), fibrosis stage 2 or 3 (F2-F3). The study has reported statistically significant improvements in histological endpoints, demonstrating a significant response rate for fibrosis improvement without worsening of MASH in patients treated with EFX.
The response rates on the primary endpoint of ≥1 stage improvement in fibrosis without worsening of MASH increased to 75% for the 50mg EFX group and 46% for the 28mg EFX group at week 96, compared to 24% for placebo. Additionally, the study met additional histology endpoints at week 96, with 36% and 31% of patients treated with 50mg and 28mg EFX, respectively, experiencing a 2-stage improvement in fibrosis without worsening of MASH, which is more than 10-fold the placebo rate of 3%.
The placebo-adjusted effect size on fibrosis improvement without worsening of MASH more than doubled between week 24 and week 96 for the 50mg EFX group, with a slight increase observed for the 28mg EFX group. The study also indicated sustained response, particularly at 50mg EFX, with 92% of the 50mg EFX group remaining responders among those patients with available week 96 biopsies whose fibrosis improved at week 24, compared to 40% for placebo.
In terms of safety, EFX was reported to be generally well-tolerated with no deaths. The most frequent adverse events were grade 1 or 2 gastrointestinal events, which were transient in nature. There were a total of fifteen serious adverse events reported, which were generally balanced across dose groups.
Akero's President and CEO, Andrew Cheng, M.D., Ph.D., expressed optimism about the results and highlighted the potential of EFX to yield sustained fibrosis improvement and widening anti-fibrotic treatment responses across the treated patient populations.
The company is currently evaluating EFX in patients with pre-cirrhotic MASH and cirrhosis due to MASH in its ongoing phase 3 Synchrony program, with two out of three studies actively enrolling.
MASH is a serious form of metabolic-associated steatohepatitis estimated to affect more than 17 million Americans. It is characterized by an excessive accumulation of fat in the liver that causes stress and injury to liver cells, leading to inflammation and fibrosis, which can progress to cirrhosis, liver failure, cancer, and eventually death. There are currently no approved treatments for the condition.
The phase 2b Harmony study enrolled a total of 128 patients and the primary efficacy endpoint for the study was the proportion of subjects who achieved at least one-stage fibrosis improvement without worsening of MASH at week 24.
EFX, Akero's lead product candidate for MASH, is currently being evaluated in the ongoing phase 2b Symmetry, phase 3 Synchrony Histology, and phase 3 Synchrony Real-World studies. It has been observed to reduce liver fat and inflammation, reverse fibrosis, increase insulin sensitivity, and improve lipoproteins in multiple clinical trials.
Akero Therapeutics is a clinical-stage company developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, including MASH. The company's phase 3 Synchrony program builds on the results of two phase 2b clinical trials, the Harmony study in patients with pre-cirrhotic MASH and the Symmetry study in patients with cirrhosis due to MASH.
The market has reacted to these announcements by moving the company's shares 14.6% to a price of $31.86. For more information, read the company's full 8-K submission here.
