NGM Bio today announced data from a Phase 2 study of its lead product candidate, NGM282, demonstrating clinically meaningful improvements in histological measures of disease in nonalcoholic steatohepatitis (NASH) patients at twelve weeks. NGM282, an analogue of the human hormone FGF19, showed a rapid and robust impact on both fibrosis stage and disease activity as measured by non-alcoholic fatty liver disease (NAFLD) activity score (NAS) in this open-label study of NGM282. Comprehensive data from this Phase 2 study will be presented in a plenary session at The International Liver Congress 2018 in Paris.
"It is unprecedented to see such profound histological improvement in well-established NASH after only twelve weeks of treatment, confirming that NGM282 is potently impacting many clinical dimensions of the disease," said Stephen A. Harrison, M.D., Medical Director at Pinnacle Clinical Research, Visiting Professor of Hepatology at University of Oxford, UK and principal investigator on the Phase 2 study. "These data reinforce the potential of NGM282 to resolve disease and reverse fibrosis across a broad range of NASH patients, strongly supporting the continued development of NGM282 in NASH."
The Phase 2 trial evaluated the efficacy, safety and tolerability of daily subcutaneous injections of 3 mg NGM282 over 12 weeks of treatment in patients with biopsy-confirmed NASH. Twenty-two patients were enrolled, nineteen completed the study with paired biopsies, and three withdrew early for reasons unrelated to the drug.
A blinded, pooled reading of patient biopsies at baseline and after 12 weeks of therapy demonstrated that eight of nineteen NGM282-treated patients had liver fibrosis improve by at least one stage from baseline, with three patients demonstrating a two-stage improvement in fibrosis (all F3 to F1). After 12 weeks, 84% of patients saw improvement in their NAS, with 58% of patients achieving an improvement in NAS of >2 points with at least one point of improvement in either inflammation or ballooning. These changes in histology were consistent with the degree and rapidity of improvements seen in non-invasive measures of NASH, including MRI-PDFF measures of LFC and serum biomarkers of liver inflammation, lipid metabolism and fibrosis.
NGM282 is a non-tumorigenic engineered variant of the human hormone FGF19 that reduces liver fat content, improves liver function and reverses fibrosis by targeting multiple pathogenic pathways of liver disease. NGM Bio has generated robust preclinical and clinical evidence supporting the ability of NGM282 to resolve disease and reverse fibrosis in NASH patients. This wholly-owned therapeutic has been evaluated in four Phase 2 studies in primary biliary cholangitis, primary sclerosing cholangitis, type 2 diabetes and NASH. NGM282's safety database includes clinical data from more than 400 individuals.
While NGM282 is wholly owned by NGM Bio it is also partnering with Merck on a number of other drugs in development.