Novartis, Conatus' emricasan fails mid-stage NASH fibrosis trial

Shares in Conatus Pharmaceuticals dropped as much as over 50 percent after the company announced that the experimental pan-caspase inhibitor emricasan failed to achieve the primary endpoint in the Phase IIb ENCORE-NF trial of patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and liver fibrosis. "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 CEO Steven Mento. He noted that additional data readouts are expected over the coming months and that Conatus will "[review] the totality of these results with our collaborators at Novartis to determine the most appropriate path forward." 

ENCORE-NF enrolled 318 patients with biopsy-confirmed NASH CRN fibrosis stages F1-F3 at baseline. Participants were randomised to treatment with emricasan, at a dose of either 5 mg or 50 mg, or placebo twice daily for 72 weeks. The primary endpoint was CRN fibrosis improvement of at least one stage with no worsening of steatohepatitis at week 72 versus placebo. 

Top-line results showed that the response rates in the low-dose and high-dose emricasan groups were 11.2 percent and 12.3 percent, respectively, versus 19 percent for placebo. Conatus said findings also revealed "significant reductions" in ALT, caspase 3 and caspase 7 levels in both emricasan groups relative to placebo, while safety results for the oral drug were consistent with previous findings. 

Shares in Conatus plunged by more than half last December after the company reported that emricasan had also failed to meet the primary endpoint of the mid-stage ENCORE-PH study at 24 weeks of patients with NASH cirrhosis and severe portal hypertension.The company said it is completing a six-month extension of ENCORE-PH with liver function and clinical outcome results after 48 weeks of treatment are expected in mid-2019. Meanwhile, Conatus expects data by the middle of the year from the ENCORE-LF study, which involves patients with decompensated NASH cirrhosis. 

Novartis signed a deal with Conatus in 2016 to jointly develop oral treatments for chronic liver diseases. The Swiss drugmaker exercised an option for an exclusive global licence for emricasan the following year. 

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