EASL: Experimental drug slashes fatty liver markers in Phase 2
- South San Francisco-based NGM Biopharmaceuticals presented fat-busting Phase 2 data on its lead compound, NGM282, in nonalcoholic steatohepatitis (NASH); the data was chosen as the closing oral late-breaker session at the International Liver Congress (EASL), currently ongoing in the Netherlands.
- In the 12-week, placebo-controlled study, 79% of patients treated with NGM282, a non-tumorigenic, engineered variant of the human hormone FGF19, met the study's primary endpoint, which was a decrease of at least 5% in liver fat content. Looking at both 3 mg and 6 mg doses, all patients had statistically and clinically meaningful declines in liver fat levels, and 34% showed normal liver fat content at 12 weeks. The biggest changes were in people with the highest fat levels and most active disease. Triglyceride levels also decreased, by 39 mg/dl and 44 mg/dl for the 3mg and 6 mg.
- Most adverse events were mild and dose dependent, most commonly lower gastrointestinal symptoms, nausea and injection site erythema. There was one serious adverse event (acute pancreatitis) in the 3 mg group.
Non-alcoholic fatty liver disease (NAFLD), usually seen in overweight and obese people, is caused by a build-up of fat in the liver. In its early stages it doesn't have a major impact, but around a fifth of people with NAFLD will develop nonalcoholic steatohepatitis (NASH). NASH-associated liver fat, inflammation, tissue damage and scarring can lead to liver cancer and liver failure. NASH affects as many as 400 million people worldwide, with no approved therapies currently available.
With NGM282, NGM Biopharmaceuticals' aim is to create a drug that fully resolves nonalcoholic steatohepatitis (NASH) and returns the liver to health.
"The clinical data… confirms our original conviction that FGF19 plays a critical role in regulating liver and metabolic functions in patients who have had gastric bypass surgery, which is currently the only curative treatment for patients with NASH," said Alex DePaoli, CMO of NGM Bio.
This is still early stage data so far, but the medics involved are hopeful.
"There is an urgent need to develop pharmacologic treatments that can help NASH patients restore their liver health. NGM282 is the first agent I’ve tested that holds the potential to completely reverse steatosis in as short as 12 weeks of therapy,” said Stephen A. Harrison, medical director at Pinnacle Clinical Research and visiting professor of Hepatology at the Radcliffe Department of Medicine at University of Oxford, UK.
Despite the lack of currently available treatments, however, NGM Bio isn't going to have the stage to itself. Currently in the race to market are Intercept Pharmaceuticals, which has been allowed to cut its recruitment goal by half for its Phase 3 REGENERATE study; Allergan and Novartis, which have teamed up to evaluate a combination of Allergan's cenicriviroc and Novartis' LJN452 in a Phase 2b study; and Cempra, which is taking an antibiotic approach and has positive interim Phase 2 data.
NGM Bio isn't putting all its eggs into one drug and indication basket. NGM282 has also been assessed in Phase 2 studies in primary biliary cholangitis and type 2 diabetes, and a Phase 2 trial in primary sclerosing cholangitis is expected to readout in the second half of this year.
Back in 2015, NGM Biopharmaceuticals signed a multi-year deal with Merck & Co to collaborate on novel biologic therapies across a wide range of therapeutic areas, including diabetes, obesity and nonalcoholic steatohepatitis (NASH). While NGM282 is not part of the deal, Merck's involvement in the company and the field supports the importance of therapeutics for NASH.
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