AMSTERDAM — A pegylated form of the hormone FGF21 injected subcutaneously produced improvements in hepatic fat, fibrosis markers and metabolic parameters, according to data presented at the International Liver Congress.
“BMS-986036 10 mg daily and 20 mg weekly for 16 weeks, compared with placebo, significantly decreased hepatic fat fraction in patients with NASH and fibrosis 1 through 3,” Arun Sanyal, MD, from Virginia Commonwealth University, said during his late breaker presentation. “BMS-986036 daily and weekly — relative to placebo — was associated with improvements in biomarkers of fibrosis, metabolic parameters and markers of hepatic injury.”
Sanyal and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study using BMS-986036 (Bristol-Myers Squibb). They recruited adults with BMI 25 kg/mg2 or greater, NASH as confirmed by biopsy and hepatic fat fraction at 10% or greater as determined by MRI-proton density fat fraction (MRI-PDFF).
After a 1-week lead-in placebo period to ensure compliance with injections, patients received injections of either of BMS-986036 10 mg daily (n = 23), 20 mg weekly (n = 21) or placebo daily (n = 24) for 16 weeks. At baseline, all groups were similarly matched.
At week 16, both BMS-986036 groups showed reduced hepatic fat fraction; the 10-mg group saw a 6.8% reduction (P = .0004 compared to placebo) while the 20-mg group saw a 5.2% reduction (P = .008 compared to placebo).
“A relative reduction of 29% or greater in MRI-PDFF produced a histologic response in NASH patients,” Sanyal said.
In comparison to placebo, where 25% of patients reached that 30% relative reduction threshold, 57% of patients receiving 10 mg (P = 0.279) and 52% of patients receiving 20 mg (P = .0566) of the study drug met the same endpoint.
When looking at adiponectin, Sanyal reported that the placebo group saw a –2.3% change, while the BMS-986036 10 mg group saw a 15.3% increase (P = .0071) and the 20-mg group saw a 15.9% increase (P = .0072). Similarly, triglycerides, LDL and HDL cholesterol improved in the treatment groups but failed to improve with placebo.
Over the course of the study, improvements occurred with regard to enzymes alanine aminotransferase and aspartate aminotransferase in the treatment groups but not in the placebo group.
Using MR elastography (MRE), Sanyal showed categorical improvement in liver stiffness. Just seven patients in the placebo group experienced a 15% or greater reduction in liver stiffness while BMS-986036 10 mg achieved the same goal in 36% of patients and 33% of the 20 mg group reported the same.
There were no serious adverse events in any of the treatment groups and most adverse events were considered mild.
“These results suggest that the compound has beneficial effects on steatosis, liver injury and fibrosis in NASH,” Sanyal said. – by Katrina Altersitz
Sanyal A. LBO-02. Presented at: International Liver Congress; April 19-24, 2017; Amsterdam.
Disclosure: This study was supported by Bristol-Myers Squibb.