In February, NGM Bio reported that its Phase 2 clinical trial of NGM282 in patients with primary sclerosing cholangitis (PSC) did not meet its primary endpoint.
Data from the randomized, double-blind, placebo-controlled study revealed that the drug did not produce a statistically significant change in alkaline phosphatase (ALP), a presumptive biomarker of PSC disease progression, from baseline to week 12.
The company announced this morning that it will be highlighting the data in a late-breaking plenary presentation at The International Liver Congress (ILC) 2018 in Paris tomorrow, Saturday, April 14,
NGM282, a non-tumorigenic engineered variant of the human hormone FGF19, has been developed to reduce liver fat content, improve liver function and reverse fibrosis by targeting multiple pathogenic pathways of liver disease. Despite its failure to meet the primary endpoint, it was consistent with historical studies in other diseases of the liver. It demonstrated both statistically significant improvements in the biomarkers of hepatic injury and fibrosis, as well as statistically significant reductions in biomarkers of bile acid synthesis and serum bile acids.
"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 in a press release
. "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."
Hirschfield served as a principal investigator of the study and will present the results tomorrow at the ILC meeting.
The proof of concept study enrolled 62 patients with PSC who had an elevated ALP level (≥1.5x the upper limit of normal), and randomized them to receive either NGM282 1 mg or 3 mg, or placebo, once daily via subcutaneous injection.
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 meaningfully decreased in both NGM282 cohorts at week 12 versus placebo. Additionally, markers of fibrosis were also reduced in both NGM282 cohorts, with the greatest effect in patients with more severe disease and greater risk of disease progression.
In addition to the research conducted in PSC, NGM282 has also been evaluated in four Phase 2 studies in primary biliary cholangitis, type 2 diabetes and nonalcoholic steatohepatitis (NASH). NGM282's safety database includes clinical data from more than 400 individuals.
"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,” said Alex DePaoli, M.D., NGM Bio's Chief Medical Officer.
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