South San Francisco-based Akero Therapeutics presented results on Tuesday from a 16-week analysis of secondary and exploratory endpoints in its Phase IIa BALANCED clinical trial of efruxifermin (EFX) in nonalcoholic steatohepatitis (NASH).
NASH is a form of fatty liver disease that can lead to cirrhosis but is found in people with little or no alcohol use. It is linked to the obesity and diabetes crisis. There are no specific treatments approved.
Of the 40 patients who responded who had end-of-treatment biopsies, 48% showed at least a one-stage improvement in fibrosis (scarring) without worsening of NAFLD activity score (NAS) and 28% demonstrated at least a two-stage improvement in fibrosis. Also, 48% of responders hit NASH resolution without the fibrosis getting worse. There were also improved glycemic control and dyslipidemia (high triglyceride, cholesterol or fat phospholipids), in addition to weight loss, across all levels of dosages. The treatment was generally well tolerated.
“These substantial improvements observed in multiple measures of liver health, particularly the one- and two-stage improvements in fibrosis, are extremely encouraging and among the strongest biopsy results reported in NASH to date,” said Stephen Harrison, medical director of Pinnacle Clinical Research. “I believe efruxifermin continues to set itself apart as one of the most promising drug candidates in NASH, with impressive histology results after just 16 weeks of treatment.”
EFX was originally developed by Amgen for diabetes, that Akero licensed from Amgen. In March, Akero reported that the drug had better results than placebo in reducing liver fat in NASH patients. This new data further has investors and analysts intrigued.
Analysts with Jefferies wrote in a note, “Overall, the drug appears to have big benefits on the two key problems with NASH that no other drug has shown: (1) improved liver histology and fibrosis, (2) improvements in diabetes parameters and improved lipids, and (3) notable positive weight loss benefits, all in one.”
The expected leader in the race to get a NASH therapy approved was Intercept Pharmaceuticals. However, on June 29, the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to the company’s New Drug Application (NDA) for obeticholic acid (OCA) for fibrosis from NASH. The CRL said that based on the data the agency had reviewed, they did not believe the predicted benefit of the drug based on a surrogate histopathologic endpoint was ambiguous and did not outweigh the potential risks to support accelerated approval. The FDA recommended the company submit additional post-interim analysis efficacy and safety data from its ongoing REGENERATE trial.
Another biotech company in the space, France’s Inventiva, reported on June 15 that its lanifibranor for NASH had positive topline results in its Phase IIb NATIVE trial. It met the primary endpoint in the intent-to-treat population, demonstrating a statistically significant decrease of at least two points in the SAF activity score compared to baseline, with no worsening of fibrosis. In the lanifibranor 1200mg/day dose group, 49% of the patients hit the primary endpoint compared to 27% in the placebo arm.
Of today’s news, Akero’s president and chief executive officer, Andrew Cheng, said, “We believe the BALANCED study data, which exceeded our expectations, demonstrate the strong potential of efruxifermin to be a foundational monotherapy for the treatment of NASH. We look forward to the continued development of efruxifermin and are working diligently to deliver this potentially leading treatment to patients. We are extremely grateful to all of our investigators and study patients, particularly given that this study cohort was completed amidst the COVID-19 pandemic.”