NGM Bio Announces Late-Breaking Plenary Presentation At International Liver Conference 2018 Of Detailed Results From Phase 2 Study Of NGM282 In Patients With Primary Sclerosing Cholangitis
As previously reported, study did not meet primary endpoint of statistically significant change in alkaline phosphatase
Statistically significant improvements seen in biomarkers of hepatic injury and fibrosis
Statistically significant reductions seen in biomarkers of bile acid synthesis and serum bile acids
PARIS, FRANCE AND SOUTH SAN FRANCISCO, APRIL 13, 2018 -- NGM Bio today announced that detailed data from an exploratory Phase 2 study of patients with primary sclerosing cholangitis (PSC) who were treated with NGM282, an engineered analogue of FGF19, will be highlighted in a late-breaking plenary presentation at The International Liver Congress (ILC) 2018 in Paris tomorrow, Saturday, April 14, at 4:15 PM CEST. PSC is a rare, life-threatening, chronic cholestatic liver disease with no currently approved therapeutic treatments. As previously reported, the randomized, double-blind, placebo-controlled Phase 2 study did not meet its primary endpoint of statistically significant change in alkaline phosphatase (ALP), a presumptive biomarker of PSC disease progression, from baseline to week 12. However, NGM282 demonstrated both statistically significant improvements in biomarkers of hepatic injury and fibrosis, as well as statistically significant reductions in biomarkers of bile acid synthesis and serum bile acids, all consistent with past studies of NGM282 in other liver diseases. NGM282 met the secondary endpoints in the study and was generally safe and well tolerated by study subjects.
“These are highly encouraging results, as they suggest NGM282 has the ability to impact multiple dimensions of PSC, for which there currently are no approved therapeutic options beyond liver transplantation,” said Professor Gideon Hirschfield from the University of Birmingham in the UK, who served as a principal investigator of the study and will present the results tomorrow at the ILC meeting. “In showing improvement in markers of fibrosis and liver function, NGM282 demonstrated a positive effect on these patients’ livers that we have not previously seen.”
About the Study Findings
The Phase 2 study enrolled 62 patients with PSC who had an elevated ALP level (≥1.5x the upper limit of normal). Patients were randomized to receive NGM282 1 mg or 3 mg, or placebo, once daily via subcutaneous injection. The primary endpoint was the change in ALP from baseline to week 12. While there were no significant reductions in serum ALP levels in either active treatment cohort compared to placebo, significant reductions in serum levels of alanine aminotransferase (ALT) (-40 U/L) and aspartate aminotransferase (AST) (-23 U/L) were observed in the 3 mg cohort at week 12 (p<0.01 vs. placebo). Serum levels of 7α-hydroxy-4-cholesten-3-one (C4), an indicator of bile acid synthesis, and total bile acid were also significantly reduced in both NGM282 cohorts at week 12 compared with placebo. In addition, markers of fibrosis (Enhanced Liver Fibrosis (ELF) Score, PIIINP, TIMP-1 and PRO-C3) were also reduced in both NGM282 cohorts, with the greatest effect in patients with more severe disease and greater risk of disease progression.
NGM282 demonstrated a favorable safety and tolerability profile in PSC patients, consistent with previous clinical studies of the drug in other patient populations. The most common adverse events were diarrhea, frequent stools and injection site reactions, the majority of which were mild and resolved on therapy. There were no meaningful changes in lipid parameters or triglycerides during the treatment period.
“We’d like to thank the patients, the PSC advocacy community, and the study investigators and staff who supported this study, which we hope will advance our collective understanding of the pathogenesis of PSC and the therapeutic benefit NGM282 could provide for these patients,” said Alex DePaoli, M.D., NGM Bio’s Chief Medical Officer. “While we are currently focused on advancing NGM282 as a potential treatment for NASH, we will continue to interrogate and fully understand these data in PSC, particularly with respect to the ongoing dialogue regarding appropriate surrogate endpoints for the disease.”
Data from NGM Bio’s exploratory Phase 2 study of NGM282 in nonalcoholic steatohepatitis (NASH) patients also will be presented tomorrow at ILC during a 10:15 AM CEST plenary session. In that study, NGM282 demonstrated statistically significant and clinically meaningful improvements in histological measures of NASH after just twelve weeks of treatment.
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 nonalcoholic steatohepatitis (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
About Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC) is a rare, life-threatening, chronic cholestatic liver disease characterized by progressive destruction of bile ducts that leads to the development of cirrhosis and end-stage liver disease or cancer in a majority of patients. In patients with PSC, the bile ducts become blocked due to inflammation and scarring, or fibrosis. This causes bile to accumulate in the liver, where it gradually damages liver cells and causes cirrhosis of the liver. As cirrhosis progresses and the amount of scar tissue in the liver increases, the liver slowly loses its ability to function. The scar tissue may block drainage of the bile ducts, leading to infection of the bile ducts. There are no approved therapies for PSC, and estimated survival time from PSC diagnosis to liver transplant is approximately 10 years. Males are slightly more likely to contract PSC, and as many as 75% of patients have concomitant inflammatory bowel disease, most often ulcerative colitis. Although it is a rare disease, PSC is the seventh leading indication for liver transplant in adults in the United States.
About NGM Bio
NGM Bio is a research-driven biotechnology company committed to discovering and developing novel biologics for the treatment of life-threatening diseases. NGM Bio’s portfolio consists of multiple programs in clinical testing and more than a dozen additional programs in various stages of preclinical development. The company’s most advanced compound, NGM282, is a wholly-owned asset that is in Phase 2 testing for nonalcoholic steatohepatitis (NASH). NGM Bio has established a broad strategic collaboration with Merck. NGM Bio is backed by The Column Group, Merck, Prospect Ventures, Topspin Partners, Rho Ventures, Tichenor Ventures and other leading investors around the world. For more information, please visit www.ngmbio.com.