Genfit Dives Into Uncertain Late-stage NASH Trial
This article was originally published in Scrip
Despite previously disappointing results, Genfit made good on earlier promises Nov. 16 when it announced that it is moving its NASH candidate into Phase III based on feedback from regulatory agencies.
The French biotech will begin an 1,800-patient late-stage trial of elafibranor (GFT505) before the end of the year in patients with advanced non-alcoholic steatohepatitis (NASH). The trial will take place at 200 sites around the world and will test the 120mg daily dose against a placebo.
"Based on our recent discussions with agencies, we agreed that approval may be obtained after an interim analysis at 72 weeks of treatment based on a histological endpoint of NASH resolution," said Genfit Chairman and CEO Jean-Francois Mouney. "The new consensual definition of resolution of NASH, which corresponds to the absence of ballooning and the absence or mild inflammation, is well aligned with the efficacy of elafibranor."
Genfit will have the ability to file for approval of elafibranor with FDA after the interim analysis – likely 2018. The interim results will be conducted once 900 patients have been enrolled and the late-stage trial will continue after approval as a post-marketing study.
Why It Matters
Investors and analysts will pay close attention to the interim results because of the spotty efficacy results Genfit has announced in the past for the drug. In March, the biotech announced mixed results from the Phase II GOLDEN study. Elafibranor failed to show a resolution of NASH without worsening of fibrosis when compared to placebo.
Genfit attributed the results to the patient population, as well as the number of clinical trial sites that had a small number of patients. GOLDEN-505 included NASH patients who had a NAFLD Activity Score (NAS) equal to three, indicating early disease, up to patients with a NAS equal to eight, indicating severe disease. Genfit argues that the inclusion of these less sick patients skewed the results – there was a high placebo response of 57% in these patients.
Patients in the upcoming Phase III study will have a NAS greater than 4 and patients will have F2 or F3 level fibroids. All patients will be followed until the occurrence of a pre-defined number of progressions to cirrhosis and other liver related events.
BioMedTracker gives elafibranor a 12% chance of approval, 12% below the average. There is only one other NASH drug in Phase III, but several others in mid stages including offerings from Gilead Sciences, Tobira Therapeutics and Bristol-Myers Squibb.
Competitor Intercept pharmaceuticals has a similar design for its Phase III trial, which will include 2,500 patients at 250 worldwide sites.
Intercept's obeticholic acid (OCA) has long been considered the front-runner in this space, which analysts estimate could be worth upwards of $10bn annually. While Intercept's late-stage trial is still enrolling, recently announced results from a small Phase II study conducted in Japan were not favorable and have thrown into question whether OCA can deliver the same positive results that were seen in earlier Phase II trials.