NGM282, NAS and fibrosis in NASH

NGM282, NAS and fibrosis in NASH: a phase 2 study
Harrison SA, AASLD 2018, Abs. 104




* NAS (NAFLD Activity Score): steatosis (0 to 3), lobular inflammation (0 to 3), ballooning (0 to 2)

  • NGM282: engineered variant of human FGF19
  • Rosuvastatin: started at W2 if LDL-cholesterol rise ≥ 10 mg/dl


  • Primary: decrease in absolute liver fat content (MRI-PDFF) ≥ 5% at W12
  • Exploratory: change in liver histology at W12

Baseline characteristics, mean (SD)

Mean C4 levels (ng/ml)

* p < 0.001 vs baseline

Mean total serum bile acids (µmol/L)

Primary endpoint: mean absolute liver fat content at W12, %

  • Absolute and relative changes in LFC at W12: -11.2 % and -67% (3 mg) ; -10.9% and -57% (1 mg)
  • 100% (3 mg) and 92% (1 mg) of subjects achieved primary endpoint of ≥ 5% absolute LFC reduction
  • 100% (3 mg) and 92% (1 mg) had a relative decrease in LFC ≥ 30% at W12
  • 63% (3 mg) and 33% (1 mg) of subjects normalized LFC (≤ 5%) by W12

Mean transaminases (IU/L)

Histological parameters, %

Fibrosis at baseline and W12 in the NGM282 1 mg group

  • Mean change from baseline in fibrosis stage: - 0.1
  • One subject had a 2-stage improvement in fibrosis: F2 to F0

Safety and tolerability

  • Favorable safety and tolerability profile consistent with other NGM282 studies: no new safety signals identified
  • Mild gastrointestinal symptoms (loose/frequent stools) were the most common treatment emergent adverse events
    • Majority were mild and resolved during treatment phase
    • No subject withdrew from treatment due to any drug-related AEs
  • Gastrointestinal symptoms were largely mitigated with separating the timing of injection around meals and decreasing meal size
  • Five severe adverse events, all unrelated to study drug:
    • Pneumonia
    • Pleurisy
    • Chest tightness
    • Cardiac arrest (non myocardial infarction)
    • Renal mass


  • Potent C4 and bile acid suppression consistent with FGF19 hormone activity
  • Significant and clinically meaningful reductions across non-invasive markers of NASH-related disease
  • Large percentage of patients demonstrated histological improvement at W12
  • Statin co-administration rapidly mitigates LDL-cholesterol elevations
  • Treatment was safe and well tolerated