Genfit, once considered among the frontrunners in the biotech race to commercialize a treatment for nonalcoholic steatohepatitis (NASH), has come up short. The French company said Monday that its investigational treatment, elafibranor, did not meet the main goal of a late-stage trial evaluating its ability to resolve the fatty liver disease without worsening related scarring.
That’s according to an analysis of interim data from the RESOLVE-IT study, which looked at results from about 1,000 patients of the roughly 2,000 enrolled in the trial after 72 weeks.
Genfit (NASDAQ: GNFT) CEO Pascal Prigent, speaking on a conference call Monday, said early data from the randomized trial revealed a response rate of 19.2 percent in the patients who received 120mg of the drug once daily compared to 14.7 percent of patients who received a placebo.
Despite numerically beating the placebo, elafibrinor’s results were not enough to be statistically significant, the company said. Prigent characterized the response rate for the placebo group as unusually robust compared to similar NASH trials.
“Although the response rates observed within elafibranor treatment were broadly aligned with our initial expectations, the trial result showed a placebo response that was significantly higher than what we anticipated,” he said.
The Genfit drug also didn’t hit statistical significance on secondary measures related to improving fibrosis and metabolic parameters.
Last month SVB Leerink analyst Thomas Smith assigned the drug a 55 percent probability of meeting its main goal and a 40 percent chance of missing it. Smith assigned a 5 percent probability to a worst-case scenario in which a safety issue emerged, affecting elafibranor’s potential in primary biliary cholangitis, a chronic liver disease for which Genfit is also evaluating the drug. Genfit reported elafibranor’s safety and tolerability in RESOLVE-IT was consistent with previous studies.
Smith, in the April research note, said the company’s share price would likely fall by about 60 percent to $8 per share if it were to miss the study’s main goal. Genfit announced the trial failure after market close Monday; its shares, which closed at $21.70, fell by nearly 50 percent in after-hours trading.
There are no FDA-approved drugs for NASH, a quickly growing condition that causes liver inflammation and scarring and, for patients in whom it progresses to liver failure, requires a liver transplant. Other companies have also struggled in advancing drugs for the condition, including Foster City, CA-based Gilead Sciences (NASDAQ: GILD), whose most advanced candidate to treat the fatty liver disease, selonsertib, failed two Phase 3 trials in 2019.
However, it’s possible this is the year the first NASH treatment will receive an FDA nod. A treatment developed by New York’s Intercept (NASDAQ: ICPT) is currently under review by the agency, whose decision is anticipated by late June.
Prigent said Genfit will decide whether to stop, amend, or continue RESOLVE-IT after completing additional analyses and talking with regulators.
Typical placebo response rates in most NASH trials are in the 5 percent to 9 percent range, he said.
“This is intriguing, and we want to better understand the discrepancies,” he said.
He emphasized, however, that Genfit has no route to approval for the drug in NASH given the interim analysis from the trial, which was conducted at sites across 25 countries. The company plans to present full results from the study at a medical meeting in the second half of the year.
In the meantime, the company says it will continue as planned with a Phase 3 trial evaluating elafibranor as a treatment in patients with primary biliary cholangitis and development of NIS4, a diagnostic test for NASH designed to replace biopsies. Prigent said the company is also considering potential additions to its pipeline.