A phase 2 trial of Bristol-Myers' NASH candidate BMS-986036 met its primary endpoint. The data position Bristol-Myers to talk to regulators about further development of a drug it hopes will snag a slice of the NASH market in the face of competition from Allergan, Gilead and others.
Bristol-Myers enrolled 74 patients in the trial and randomized them to receive one of two doses of its pegylated analogue of human fibroblast growth factor 21 or a placebo. The daily and weekly doses of BMS-986036 both outperformed placebo in terms of reducing liver fat over the course of the 16-week study. Fat levels in the daily and weekly cohorts fell 6.8% and 5.2%, respectively, compared to 1.3% in the placebo group, resulting in the trial meeting its primary endpoint.
Investigators calculated more than half of participants in each of the BMS-986036 arms experienced a 30% or greater relative risk reduction.
The trial also assessed other key aspects of NASH using predefined exploratory endpoints. To gauge the effect of BMS-986036 on fibrosis, liver stiffness and liver injury, Bristol-Myers looked at the serum biomarker Pro-C3, performed magnetic resonance elastography (MRE) and tracked adiponectin, ALT and AST. Bristol-Myers said the trial linked both experimental treatment regimens to improvements in all these areas.
More than 60% of patients in the treatment arms experienced a 15% reduction in Pro-C3, compared to 18% in the placebo group. The trend in MRE was similarly strong. More than 30% patients on BMS-986036 experienced a 15% reduction, compared to 7% in the placebo arm.
The size and design of the trial makes it impossible to draw hard conclusions from these data but lead author Arun Sanyal, M.D. was encouraged by the findings.
“These data suggest that BMS-986036 may be effective in patients with NASH, many of whom will experience disease progression due to the lack of available treatment options,” Sanyal, a professor at Virginia Commonwealth University, said in a statement. “The results of this study show that BMS-986036 had beneficial effects on three important components in the treatment of NASH: Liver fat, liver injury and fibrosis.”
Diarrhea, nausea and frequent bowel movements were more common in the treatment arms than the placebo cohort. None of these events were classed as serious, though. And with the trial also wrapping up without any treatment-related deaths, serious adverse events or discontinuations, Bristol-Myers thinks it has a drug with a favorable safety profile on its hands.
The next step is to talk to regulators to figure out a path forward for the asset. Sanyal is keen to see the weekly regimen undergo further testing. Many NASH programs at comparable or more advanced stages of development, including Allergan’s cenicriviroc, Genfit’s elafibranor and Intercept’s obeticholic acid, are administered daily.