Genfit's NASH drug fails a closely-watched PhIII showdown, adding one more setback to a plagued field
Genfit’s bid to make R&D history with a storybook turnaround came to a crashing halt on Monday as the French biotech acknowledged that its Phase III study of elafibranor failed to distinguish itself from placebo in treating NASH.
The biotech had tried to prove that the drug would resolve NASH without fibrosis in a population of more than 1,000 patients. But the data came up with a 19.2% response rate for the drug arm compared to a 14.7% rate for the placebo.
Genfit CEO Pascal Prigent put down the “disappointing” result to a high placebo response, though the drug arm didn’t appear to score all that high in the study.
The CEO noted:
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. In parallel, we continue as planned with our NIS4TM and Phase 3 PBC (primary biliary cholangitis) programs, which are independent of our NASH program with elafibranor. We will provide updated guidance on our global corporate strategy later in the year, once we have more clarity on the regulatory implications of the RESOLVE-IT interim readout, as well as more visibility on the evolution of the impact of the worldwide pandemic on our ongoing studies.
Last year saw multiple setbacks in NASH, with Intercept as the sole exception to the rule. That left some analysts cautiously encouraging investors to look at Genfit, even though the odds were daunting.
SVB Leerink’s Pasha Sarraf had been on the pro-Genfit sidelines, calling this study “the most significant and volatile upcoming catalyst” they cover. “The risk/reward is not for the faint of heart.”
There were also plenty of skeptics along the way, particularly after Genfit noted a Phase II NASH failure for GOLDEN-505 in 2015, then tried to explain it all away as a failure of the trial design.
The failure leaves Intercept $ICPT as the sole winner in this field so far, with Ocaliva under review for a label expansion on NASH.
Ironically, on the same day that Genfit raised fresh questions about the PPAR class, a rival in the class — CymaBay — popped up looking for a second chance. Michael Yee at Jefferies noted:
CBAY which has a Ph II PPAR-delta focused molecule but previously halted the program due to liver-injury signals & FDA hold, announced on the same day that an independent expert panel unanimously concluded there is no evidence of drug-induced liver injury, & they will re-engage with the FDA to see if they can lift the hold. It’s unclear to us what will happen but overall we would remain cautious on the bigger picture view that a PPAR which was halted in Ph II will completely remove the safety questions until a full Ph III would be completed.