Through a randomized, double-blind, placebo-controlled phase II clinical trial, at the University of California San Diego School of Medicine report that small doses of NGM282, a non-tumorigenic variant of an endocrine gastrointestinal hormone, can significantly and rapidly decrease liver fat content in patients with non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).
A randomized, double-blind, placebo-controlled phase II clinical trial was carried out by researchers at San Diego School of Medicine to study the effect of the gastrointestinal hormone on the non-alcoholic fatty liver disease.
The reports suggested that small doses of NGM282, a non-tumorigenic variant of an endocrine gastrointestinal hormone, could significantly decrease liver fat content in patients with non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).
"Patients with NAFLD and NASH have had limited treatment options for years. What the results of our phase II study show is a promising future where NGM282 may be able to provide relief to these patients," said senior author Rohit Loomba, director of the NAFLD Research Center.
NAFLD includes a spectrum of chronic hepatic diseases, with NASH being the most aggressive type. The cause of both NAFLD and NASH remains a mystery, but certain health conditions, including obesity and type 2 diabetes, could be predisposing factors.
The study involved 166 patients, aged 18 to 75, at 18 different hospitals, gastroenterology or liver clinics in the United States and Australia. Participants had confirmed NAFLD or NASH biopsies and a liver fat content of at least 8%.
Participants were randomly assigned to a web-based computer system on a 1: 1: 1 model to receive 3 milligrams (mg) or 6 mg of NGM282 or a placebo injection once per day. They were then monitored biweekly over a three-month period.
Loomba explained that both the 3 mg and 6 mg doses of NGM282 produced a rapid and constant change of liver fat content. "The most promising outcome of this study was the absolute change in liver fat that we were able to measure using advanced magnetic resonance imaging (MRI) methods."
The method was previously developed and validated in pilot studies conducted at the NAFLD Research Center. Looking from baseline to week 12, the participants who had a liver fat reduction of at least either a 5% absolute reduction or greater than 30% relative reduction from baseline were clinically significant.
To measure the reduction in liver fat, used hepatic MRIs with proton density fat fraction. This type of imaging is extremely sensitive to changes in liver composition compared with traditional assessments of tissue samples under a microscope.
The NMG282 is a non-tumorigenic variant of fibroblast growth factor 19, an endocrine gastrointestinal hormone that regulates stomach acid and is responsible for glucose and lipid metabolism in the body.
Study participants generally tolerated NMG282 with reported side effects including pain at the injection site, diarrhea, abdominal pain, and nausea. No life-threating events or patient deaths occurred during the study.
"Moving forward, we are continuing the development of this compound for the treatment of NASH-related fibrosis," said Loomba. "In this, we hope to further examine the efficacy of this hormone in improving liver histology based end-points in patients with biopsy-proven NASH with fibrosis."