Danish diabetes giant Novo Nordisk took another step this week in its efforts to establish a presence in nonalcoholic steatohepatitis, or NASH, a metabolic disorder closely related to diabetes that is anticipated to become the leading cause of liver transplants in the US in coming years.
The company Thursday announced it had inked a deal with Ube Industries, a Japanese industrial conglomerate, for worldwide rights to UD-014, a preclinical small molecule drug that it plans to advance as a potential NASH treatment. Novo said Ube’s research showed the compound acted to reduce inflammation. Financial terms weren’t disclosed.
Unlike other fatty liver diseases, which are linked to alcohol abuse or medication side effects, NASH falls within a spectrum of conditions referred to as nonalcoholic fatty liver diseases (NAFLD) that are related to obesity and type 2 diabetes. Untreated, the fat accumulation and inflammation in the liver caused by NASH can lead to scarring, called fibrosis, and impaired liver function. As function fails, some patients progress to end-stage liver disease, liver cancer, and the need for a replacement organ. In the US, the condition is now the second-most common reason for liver transplantation.
As the prevalence of NASH continues to rise, fueled by the obesity epidemic and sugary diets, companies are racing to discover and develop ways to treat it. No FDA-approved drugs currently exist for the disease.
The Ube deal represents a doubling down by Novo when it comes to NASH. Previously its pipeline of treatments for the condition consisted of one drug, semaglutide, a once-daily injectable treatment for type 2 diabetes that the company wants to also develop for NASH.
In addition to testing semaglutide alone, Novo is also studying it in a Phase 2 trial in combination with two investigational drugs from Foster City, CA-based biopharma Gilead Sciences (NASDAQ: [[ticker:GILD]]). About six months ago the companies announced they would run a proof-of-concept clinical trial in NASH testing combinations of compounds from their respective pipelines. The Phase 2 trial, for which the companies are now recruiting, is testing semaglutide and two investigational Gilead drugs, cilofexor and firsocostat, alone and in combinations to see if the treatments improve liver damage.
Many other companies have been busy making deals in the NASH space. About a year ago, Roche acquired San Diego’s Jecure Therapeutics, looking to advance its preclinical work on developing drugs that target a complex of proteins that play a role in inflammation.
So far, however, getting a treatment across the finish line has proved elusive.
Gilead’s most advanced investigational drug for the condition failed a Phase 3 trial in February. And this summer, San Diego’s Conatus Pharmaceuticals (NASDAQ: [[ticker:CNAT]]) was forced to start exploring strategic alternatives after emricasan, a potential NASH treatment it had been developing with Novartis, didn’t meet the primary goal established for a clinical trial.
However, the first-ever NASH treatment could be approved in the coming months. New York City-based Intercept Pharmaceuticals (NASDAQ: [[ticker:ICPT]]) in September asked the FDA to review its drug obeticholic acid, which is approved to treat the liver disease primary biliary cholangitis, as a NASH therapy.
Rivals are raring to follow. A NASH drug developed by France’s Genfit (NASDAQ: [[ticker:GNFT]]), elafibranor, is in late-stage clinical testing; interim results from its Phase 3 trials are anticipated in the first quarter of 2020.
