Background: NGM282 is an engineered variant of human FGF-19 that retains bile acid and metabolic regulatory activities while eliminating the tumorigenic effects of FGF-19. Multiple preclinical models showed improvements in NASH liver histology similar to those observed post-bariatric surgery. Data from a Phase 2 trial in NASH patients showed significant reductions in hepatic steatosis, liver transaminases and markers of fibrosis that were translated to histologic benefits in NASH. Both T2D status and statin therapy have been variably associated with treatment response in NASH trials. This analysis assessed NGM282 impact on liver fat content by T2D status and statin usage.
Methods: Patients with biopsy-confirmed NASH (n=82) were randomized to NGM282 3 or 6mg or placebo for 12 weeks. The primary endpoint was ≥5% reduction in absolute liver fat content (LFC) by MRI-PDFF. Patients were stratified by T2D status at baseline and categorized as statin/no statin use (3 months prior to screening). Statin therapy was stable during the study. Treatment responses were analyzed using an ANCOVA model; NGM282 treatment arms were pooled (n=53).
Results: T2D and statin use was present in 62% and 45% of the NGM282 treated patients, respectively. There was no significant difference in LFC reduction in patients with T2D vs. no T2D (-10.4% vs.-11.2%, p=0.59) or statin use vs. no statin use (-10.7% vs. -10.7%, p=0.99) at baseline. Absolute LFC was decreased by -9.7% and -11.9% for NGM 282 3 and 6mg (p<0.001 for both), respectively. Reductions in LFC correlated with improvements in C4, HbA1c and triglycerides.
Conclusions: NGM282 is highly effective in reducing LFC, independent of T2D status or statin use. These data support the activity of NGM282 in NASH across a broad patient population. Ongoing studies will evaluate the translation of these effects into improvements in fibrosis and resolution of NASH.
A. DePaoli: Research Support; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. S.J. Rossi: Employee; Self; NGM Bio. Stock/Shareholder; Self; NGM Bio. L. Ling: Employee; Self; NGM Biopharmaceuticals. Stock/Shareholder; Self; NGM Biopharmaceuticals. S.A. Harrison: Research Support; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S. Research Support; Self; NGM Bio. Advisory Panel; Self; NGM Bio. Consultant; Self; NGM Bio. M.F. Abdelmalek: Advisory Panel; Self; NGM Bio. Consultant; Self; NGM Bio. Research Support; Self; NGM Bio. M.R. Jaros: Consultant; Self; NGM Bio. R. Somaratne: Employee; Self; NGM Biopharmaceuticals. Stock/Shareholder; Self; NGM Biopharmaceuticals.