Conatus Pharma’s lead drug emricasan missed the mark in its first midstage clinical test, driving down its stock despite the company’s efforts to put a positive spin on the data.
Jittery about the importance to San Diego-based Conatus of emricasan—and deep-pocketed partner Novartis which paid $50 million up front for rights to the drug at the end of 2016 and firmed up the partnership last year—investors wiped almost 30% off the biotech’s share price in after-hours trading.
The first phase 2 read-out for the caspase inhibitor drug is in patients with in liver transplants damaged by recurrent hepatitis C virus (HCV) infection, and emricasan was indistinguishable from placebo on the response rate, measured using the Ishak histological scoring system for liver fibrosis, for the overall patient population.
Conatus CEO Steve Mento, Ph.D., said on a conference call that the company had put a 15% improvement over placebo in the POLT-HCV-SVR trial as a threshold for further evaluation of emricasan, and while this wasn’t met for the overall cohort, it was seen in subgroups of patients with more severe fibrosis at enrollment.
“We believe that our data are the first demonstration of emricasan’s anti-fibrotic activity by histology,” he asserted, adding that this serves as proof-of-concept for the drug “in multiple subgroups of fibrosis and cirrhosis patients.”
That included patient groups with advanced fibrosis/early cirrhosis (F3, F4 and F5), which is the key target population for Conatus and had a 37% difference, according to Mento. An unexpectedly high placebo response rate in the most severely affected group (F6) skewed the data and the reasons behind that are still being explored.
“Take those out and it’s a highly successful study,” he said, adding: “We also plan to evaluate responses in additional subgroups in a variety of secondary and exploratory endpoints to learn as much as possible from this data-rich trial.”
All eyes will now be on additional data read-outs due in the coming months in nonalcoholic steatohepatitis (NASH), a much larger market opportunity for the drug. That includes the ENCORE-PH and ENCORE LF trials of the drug in NASH cirrhosis—due to report in the second half of 2018 and 2019 respectively—and the ENCORE-NF study expected in the first half of next year.
Commenting on the possible implications of the study on the Novartis deal, Mento was understandably tight-lipped but did say that emricasan remains one of the only drugs in development with a "pure" anti-fibrotic effect, as most other drugs for NASH rely on other mechanisms.
Emricasan also has anti-inflammatory effects but these were less relevant in the post-transplant population as patients had little evidence of active inflammation at baseline. Inflammation is, of course, a key component in NASH, but Conatus stopped short of speculating how that might be a factor in its NASH trials of emricasan.