Enanta Steps Forward in NASH Race, With Unclear Prospects

Xconomy Boston — 

Enanta Pharmaceuticals late Wednesday became the latest of a number of companies to tout an emerging potential therapy for nonalcoholic steatohepatitis, the fatty liver disease that is fast becoming a global epidemic. But it’s unclear whether the experimental treatment can stand out from the crowd.

Enanta (NASDAQ: ENTA) said the higher of two tested doses of its drug EDP-305 succeeded in a 12-week Phase 2 trial, ARGON-1, in 132 patients likely to have NASH. A lower dose failed.

Specifically, a 2.5 mg dose of EDP-305 helped reduce levels of the enzyme ALT by 28 units per liter of blood (U/L), or 35 percent, compared to a 15 U/L reduction (20 percent) for placebo patients after 12 weeks of treatment. High ALT levels are a sign of possible liver damage and lowering them was the main goal of Enanta’s trial.

Enanta said the liver fat levels of patients on a 2.5 mg dose of EDP-305 were cut by an average of about 31 percent after 12 weeks, versus a 12 percent reduction for placebo patients. Lowering liver fat was a secondary study goal.

The most common side effects associated with treatment were itching, stomach problems (nausea and vomiting), headache, and dizziness. Enanta said over half of the patients on its 2.5 mg dose had itching, and 20.8 percent of them dropped out of the study as a result. Enanta plans to start a longer Phase 2 trial of EDP-305 next year.

EDP-305 is what’s known as an FXR agonist, and it’s one of several in clinical development for NASH, a liver disease driven recently by the obesity epidemic and sugary diets. NASH occurs when the livers of a portion of patients with fatty liver disease become inflamed, stiff, and scarred. It leads to thousands of liver transplants a year in the US alone. There are no marketed drugs for NASH, but a slew of potential treatments are in clinical testing, many of which are FXR agonists. The furthest along, obeticholic acid, from Intercept Pharmaceuticals (NASDAQ: ICPT), could become the first-ever approved NASH drug next year.

But OCA is imperfect, causing itching and potentially worrisome increases in cholesterol. Enanta’s drug, as well as others in clinical testing from Gilead Sciences (NASDAQ: GILD) and Novartis (NYSE: NVS), aim to show that they are superior. In a statement, the study’s lead investigator, Vlad Ratziu of Pitié-Salpêtrière Hospital in Paris, said EDP-305 “clearly displays enhanced efficacy” over several other FXR drugs in clinical development. Enanta tried to back that up with a slide presentation Wednesday afternoon showing measures in which EDP-305 compares favorably to drugs from Intercept, Gilead, and Novartis.

RBC Capital Markets Brian Abrahams was more circumspect on the results. Though the drug’s effects on liver fat “appear differentiated,” he cautioned that Enanta tested a different study population than others and that it’s unclear whether the results will translate to an effect on liver scarring, an important marker for NASH drugs. Additionally, the incidence of itching in ARGON-1 “could dampen enthusiasm” for EDP-305’s potential advantages over OCA, like less of an apparent impact on cholesterol levels, Abrahams wrote.

“The once hoped for best-in-class potential seems less likely from this initial data cut,” he wrote. Enanta shares fell 10 percent, to $64 apiece.

Here’s more on NASH and some of the other drugs in clinical development.