Conatus and Novartis suffer another midphase NASH flop

Novartis
Novartis paid $50 million upfront to codevelop emricasan in 2016. (Novartis)

Conatus Pharmaceuticals’ emricasan has failed another midphase clinical trial. The latest setback saw the Novartis-partnered liver disease drug fail to beat placebo in NASH patients, wiping another 50% off Conatus’ stock price.

San Diego-based Conatus went into the phase 2b hoping to bounce back from the two midstage flops that rocked it last year but instead extended its losing streak.

The latest trial enrolled 318 patients with NASH and liver fibrosis and randomized them to receive one of two doses of pan-caspase inhibitor emricasan or placebo. Patients in the placebo arm fared better than their peers in the treatment cohorts.

Webinar

Lipid-based Formulations for Early Stage Clinical Trials

Liquid-filled capsule technology has a proven record for addressing complex API formulation challenges, but also offers a simple and effective pathway to the clinic. Register now to learn more about lipid-based formulations.

After 72 weeks, 19% of patients who received placebo had experienced a one point or greater improvement on the CRN fibrosis stage without suffering a worsening of steatohepatitis. That was the bar emricasan had to beat to hit the primary endpoint. It didn’t come close. The 5 mg and 50 mg arms chalked up response rates of 11.2% and 12.3%, respectively.

Conatus highlighted statistically significant reductions in ALT and caspase 3/7 in the treatment arms as bright spots in the dataset. There is evidence that inactivating caspase reduces hepatic cell death, but Conatus has yet to show its molecule’s effect on the enzymes translates into improved outcomes in NASH. Rather, the company has two phase 2b failures in NASH to its name. 

A third phase 2b trial is due to read out around the middle of the year, but the data generated so far have dampened expectations. Conatus responded to both phase 2b failures by arguing emricasan may be the right drug in the wrong patients. 

Last year, Conatus pointed to “clinically meaningful” improvements in a subgroup of patients with compensated NASH to argue that the drug performs better in patients with less-advanced forms of cirrhosis. This time around, the failure of emricasan in patients yet to develop cirrhosis led Conatus to argue the drug is more effective in more advanced patients.

“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,” Conatus CEO Steven Mento said in a statement.

There could be a sweet spot in the progression of NASH at which emricasan is effective, but Conatus has yet to design a trial capable of validating that idea. Instead, Conatus has generated evidence of patients in whom the drug is ineffective and driven its stock down around 70%.

Conatus expects to have data from the third phase 2b and an extension to the first study around the middle of the year. At that point, Conatus and Novartis will review the data and assess whether there is a path forward for emricasan. 

Suggested Articles

Reata’s bardoxolone improved kidney function in a phase 3 trial of patients with a rare form of chronic kidney disease.

The suit alleges the FDA imposed the hold “without notice or explanation” and has since “rebuffed” Regenxbio’s repeated requests for an explanation.

Invitae aims to expand its genetic counseling reach through the $50 million acquisition of Clear Genetics, developers of digital chatbot software.