3. Emricasan

Non-alcoholic fatty liver disease
In the phase 2b ENCORE-LF trial, emricasan wasn’t able to best placebo. (Nephron, Wikimedia Commons)

nonalcoholic steatohepatitis
Sponsors: Conatus, Novartis

Nonalcoholic steatohepatitis (NASH) has been a big focus for the pharma industry for a few years now, with dozens of treatments coming through the pipeline, but it is proving to be a tough nut to crack.

Conatus’ pan-caspase inhibitor emricasan is one of a pair of drugs for NASH that made it onto our list for 2019, and its failure cost the company a partnership with Novartis that was providing all its revenue—signed with a $50 million upfront payment in 2016—and forced it to lay off 40% of its workforce.

In the phase 2b ENCORE-LF trial, emricasan wasn’t able to best placebo on a primary endpoint that looked at whether patients died, suffered new decompensation events or experienced liver disease progression at either of two doses tested. At the same time, another study found that emricasan was no better than placebo at improving mean hepatic venous pressure gradient in compensated NASH cirrhosis patients.

The result came after unimpressive data from other readouts with emricasan, so it wasn’t a complete surprise, but its impact on Conatus has been profound.

The biotech also suspended development of preclinical-stage caspase-1 inhibitor CTS-2090 and engaged Oppenheimer & Co. to look into strategic alternatives to try to find some way to return some value to its beleaguered investors. It’s expecting to end the year with just $10 million to $15 million in cash or liquid assets, so time is running out.

Driven by rising levels of obesity and diabetes, NASH—a form of nonalcoholic fatty liver disease characterized by fibrosis and inflammation in the liver—is becoming a major healthcare concern worldwide, estimated to affect almost 1 billion people. As more people with the disease advance to cirrhosis and liver failure, it is expected to become the leading cause of liver transplants within the next decade.

It’s a complex disease, often asymptomatic and overlooked as doctors focused on underlying diabetes and excess weight in patients. For years, the development of treatments for NASH was held up by the mistaken assumption that antidiabetic drugs would help control the disease.

Even after the industry woke up to the potential, progress has been checked by failures among the lead programs, including Takeda/Shire’s apical sodium-dependent bile acid transporter inhibitor SHP626 (volixibat) in 2018 and Gilead Sciences’ ASK1 inhibitor selonsertib (also in this list). 

3. Emricasan

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