- Conatus Pharmaceuticals on Thursday disclosed its lead liver disease drug emricasan missed its primary goal in a Phase 2b study of patients with non-alcoholic steatohepatitis, or NASH, and liver fibrosis.
- A pan-caspase inhibitor, emricasan failed to show a reduction in fibrosis, or liver scarring, without worsening of NASH when compared against placebo.
- The trial, dubbed ENCORE-NF, treated 318 patients with NASH fibrosis. Patients were randomized to receive 5 mg of emricasan, 50 mg of emricasan or placebo twice daily for 72 weeks.
The setback is the third in a row for Conatus.
In December, the company revealed that its Phase 2b ENCORE-PH study also missed its primary endpoint. Despite the disappointing results, the company claimed treatment with emricasan led to a “clinically meaningful” improvement in mean hepatic venous pressure gradient (HVPG), which measures pressure in the vein system that directs blood to and from the liver.
That news came just months after emricasan failed to meet its primary endpoint in a Phase 2b trial of liver transplant patients in April 2018.
Such a string of setbacks hasn’t been taken well on Wall Street, where Friday trading sent shares in Conatus down by $1.63 per share, or 56%. Conatus’ setback appeared to spur sell-offs in other NASH-focused biotech as well, with stock in Madrigal Pharmaceuticals, Viking Therapeutics and Intercept Pharmaceuticals trading down.
ENCORE-PH and ENCORE-NF are two of three Phase 2b clinical trials that Conatus is conducting in collaboration with Novartis for fibrosis or cirrhosis caused by NASH. Results from the third study, ENCORE-LF, are expected in mid-2019, as are further data from the ENCORE-PH trial.
“Although emricasan did not have the desired effect in these earlier-stage NASH fibrosis patients, we believe its demonstrated biomarker activity across a broad spectrum of liver disease warrants continued evaluation in more advanced-stage NASH cirrhosis patients,” said Conatus CEO Steven Mento in a Thursday statement.
For now, the future of emricasan is uncertain. Conatus and Novartis will evaluate all the data from the ENCORE studies before determining the path forward for future development of emricasan, Conatus said. Novartis partnered with Conatus in 2016, paying $50 million upfront to license and commercialize emricasan.
Meanwhile, with NASH becoming a growing public health concern, other companies are rushing to bring therapies to the market. Gilead Sciences, Intercept Pharmaceuticals, Allergan and Genfit all have investigational NASH treatments in Phase 3 testing. So far this year, Gilead has reported one late-stage setback, while Intercept delivered the first — albeit qualified — positive Phase 3 result.