- French pharmaceutical company GenFit announced Monday afternoon that its main drug failed a closely watched clinical study of some 700 patients with a prominent liver disease known as NASH.
- Just over 19% of patients who took GenFit's drug had their NASH resolve without their liver scarring worsen, which was the late-stage trial's main goal. But that wasn't significantly better than the almost 15% of patients in the placebo group whose NASH also improved, causing the study to read out negative. GenFit's CEO said the placebo group did better than expected, and that his company will be running additional analyses to better understand why.
- The results deal another blow to the NASH drug field, which has seen only one late-stage study succeed. That track record is due, in large part, to the not-fully-understood biology of the disease. While GenFit has been buoyed by being one of the few companies with a NASH drug in advanced testing, Monday's announcement cut its share price in half as investors' outlook on the company dimmed.
NASH, short for nonalcoholic steatohepatitis, is a liver disease caused by the buildup of fat in the organ. While the disease is thought to affect millions of people, most don't know they have it — either because of issues with testing, or, more often, because NASH doesn't have many noticeable symptoms until its later stages.
At those later stages, however, damage to the liver can be so severe that it requires a liver transplant. NASH drugmakers have therefore been working on treatments that either resolve the disease itself or reverse its characteristic tissue scarring.
But that endeavor has proven challenging, in part because research suggests that patients can develop NASH through multiple pathways. As a result, pharmaceutical companies have struggled to find a drug that works in a wide variety of patients.
GenFit's elafibronor was one of the experimental NASH drugs farthest along in clinical testing. Though elafibranor missed the primary goal of a mid-stage trial back in 2015, GenFit said the results were affected by unexpected circumstances and decided to forge ahead into a late-stage program. Investor confidence in the drug has waned over time, especially in the last year as the company announced delays to the Phase 3 data reveal.
Ahead of the results, analysts at SVB Leerink acknowledged the "high level of investor skepticism" around what they described as the "most significant binary catalyst" this year for any of the drugmakers they cover. Had elafibranor not only led to significant NASH resolution but also a benefit on key secondary measures such as fibrosis, the SVB Leerink analysts predicted that shares could rise to a $45 to $55 price range.
Instead, Monday's disclosure from the RESOLVE-IT trial showed elafibranor didn't significantly outperform placebo in resolving NASH without patients' fibrosis getting worse. GenFit said the trial's other key secondary endpoint related to metabolic parameters did not achieve statistical significance. Shares had closed at $21.70 apiece, but were down to a little under $11 in after hours trading.
"These results are highly disappointing," Pascal Prigent, GenFit's CEO, said in a statement. "We plan to share these detailed findings with the regulatory authorities in the coming months and with their guidance, determine a final decision regarding the continuation of the RESOLVE-IT trial."
Prigent added that his company will continue its work on a NASH diagnostic test, as well as a late-stage program testing elafibranor in patients with a different liver disease known as PBC, or primary biliary cholangitis. Updated guidance on GenFit's business strategy will come later this year, according to the executive, once the company knows more about the RESOLVE-IT data and the impact of the coronavirus pandemic on its other drug programs.
More broadly, elafibranor's failure further cements the leading position held by Intercept Pharmaceuticals.
The New York-based company currently holds the only positive Phase 3 NASH results, which showed about one in four patients given a high dose of its drug, obeticholic acid, had substantial fibrosis improvement without their NASH worsening.
Intercept's drug, which is already approved to treat PBC, could be cleared for the U.S. NASH market by the end of June. Investment bank JMP Securities has modeled around $4 billion in peak NASH sales for Intercept's drug.