Enanta Axes Two Farnesoid X Receptor Agonists for NASH

Shares of Enanta Pharmaceuticals are falling this morning after the company announced plans to scrap the development of its two clinical stage farnesoid X receptor (FXR) agonists being developed as a potential treatment for non-alcoholic steatohepatitis (NASH).

Instead of continuing to develop the two different assets, EDP-305 and EDP-297, the company intends to seek an out-licensing deal that will further advance the research it began. Enanta plans to maintain its focus and resources on therapies aimed at hepatitis B virus and infectious respiratory diseases, including respiratory syncytial virus (RSV) and SARS-CoV-2, the virus that causes COVID-19. 

This morning, the Watertown, Mass.-based company said it came to its decision following a preplanned examination from a Phase IIb study of EDP-305, a monotherapy FXR agonist treatment. Although its clinical data determined that a 1 mg dose of the experimental drug provided the best safety and efficacy results, the company decided to scrap the development of the program. And that likely means that the data was not strong enough for Enanta to continue to develop the asset on its own. 

Jay R. Luly, president and chief executive officer of Enanta Pharmaceuticals, believes that the company's FXR agonists will likely do well as part of a combination treatment for NASH, a growing health concern that currently affects about 16 million people in the United States. 

EDP-305 was being developed as a monotherapy and EDP-297 was being developed as a follow-on treatment. Luly said both of the FXR agonists are “well-positioned to be an important component of a combination therapy to bring a much-needed treatment to patients with NASH.” 

The treatment, however, will have to be developed by another company. Luly pointed to the complex pathophysiology of NASH and suggested that some other companies developing therapies for NASH could benefit from Enanta’s research.

Enanta certainly isn’t the first company to fail to hit the mark in the NASH space. Nor is it the first company assessing an FXR agonist. Last year, Intercept Pharmaceuticals received a Complete Response Letter from the U.S. Food and Drug Administration for its experimental NASH treatment, obeticholic acid. Multiple companies have also struggled to achieve clinical success. 

NGM Biopharmaceuticals failed to hit the mark in a Phase IIb study assessing aldafermin, an engineered analog of the human hormone FGF19, earlier this year, while GENFIT ended its development of elafibranor for NASH following a trial failure last year. There are more than 200 different treatments in development for NASH, but none of them have succeeded in the clinic so far. 

NASH is a progressive liver disease caused by excessive fat accumulation in the liver, inducing chronic inflammation. That inflammation then results in progressive fibrosis, leading to cirrhosis, eventual liver failure, cancer, and death. Advanced fibrosis is associated with a substantially higher risk of liver-related morbidity and mortality in patients with NASH. The disease is projected to become the leading cause of liver transplants in the United States.