NGM282 in NASH: 3 mg QD (phase 2)
Harrison SA, EASL 2018, Abs. GS-014




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

  • NGM282: engineered variant of human FGF19, administered subcutaneously qd
  • Rosuvastatin: started at W2 if LDL-cholesterol rise of 10 mg/dl observed


  • Primary: decrease in absolute liver fat content = 5% at W12
  • Exploratory: change in liver histology at W12

Baseline characteristics, mean or N or %

Effect on FGF19 targets (N = 19)

C4 = 7a-hydroxyl-4-cholesten-3-one
Lower limit of C4 quantitation = 0.9 ng/ml

Primary endpoint: mean % absolute change in liver fat content at W12 (N = 19)

  • 100% of subjects achieved primary endpoint of = 5% absolute liver fat content reduction and a decreased of relative liver fat content = 30% at W12
  • 12 (63%) subjects normalized liver fat content (= 5%) by W12

Fibrosis markers changes at W12, N = 19

  • Subjects with severe disease (ELF = 10.1) decreased ELF score by 0.8 at W12

NAS histological response at W12, N = 19

Fibrosis evolution at W12 (liver biopsy), N = 19

  • Mean change from baseline in fibrosis stage: - 0.5
  • 3 subjects had a 2-stage improvement in fibrosis: all F3 changed for F1
  • Mean decrease in NAS in subjects with improved fibrosis: -3.5

Mean transaminases (U/L), N = 19

LDL-cholesterol (mg/dL) changes during treatment

  • Decreased C4 and increased LDL-cholesterol reflect potent CYP7A1 inhibition
  • Lipid particle change primarily driven by increase in large LDL particles
  • Significant reductions in serum triglycerides (56%) and no change in HDL

Safety and tolerability

  • Favorable safety and tolerability profile consistent with other NGM282 studies (no new safety signals identified)
  • Mild gastrointestinal symptoms (loose/frequent stools) remain 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 adverse events
  • Gastrointestinal symptoms were largely mitigated with separating the timing of injection around meals and decreasing meal size
  • Three severe adverse events, all unrelated to study drug:
    • Pleurisy
    • Chest tightness
    • Cardiac arrest (non myocardial infarction)


  • 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