Table 1.
Overview of Completed Phase 2 Clinical Trials Evaluating Pharmacotherapy in NAFLD That Have Moved on to Phase 3 Evaluation.
| Drug | Mechanism | Clinical trial | Phase | Duration (weeks) | Primary outcome measure | Proportion achieving outcome in treatment group | Proportion achieving outcome in control group | Result |
|---|---|---|---|---|---|---|---|---|
| Obeticholic acid | FXR agonist | FLINT | 2 | 72 weeks | ≥2-point improvement in NAS, no worsening of fibrosis | 45% | 21% | P = 0.0002 |
| Elafibrinor | PPAR α/δ agonists | NCT01694849 | 2 | 52 weeks | NASH resolution, no worsening of fibrosis | 19%* | 12% | P = 0.045 |
| Cenicriviroc | CCR-2 inhibitor | CENTAUR | 2 | 52 weeks | ≥2-point improvement in NAS, no worsening of fibrosis | Improvement in hepatocellular injury: 16%Improvement in fibrosis: 20% | Hepatocellular injury: 19% Fibrosis: 10% | P = 0.49 P = 0.02 |
| Selonsertib ± simtuzumab | ASK-1 inhibitor | 2 | 24 weeks | ≥1 stage improvement in fibrosis | 18 mg: 43% 6 mg: 30% |
20% | ||
| ≥30% Reduction in MRI-PDFF measure of liver fat |
18 mg group: 26% 6 mg group: 13% |
10% |
||||||
| ≥15% reduction in MRE-derived measures of liver stiffness |
18 mg group: 15% 6 mg group: 32% |
0% |
PPAR, peroxisome-proliferator activated receptor; FXR, Farnesoid X receptor; MRI, magnetic resonance imaging; MRE, MR elastography; NAFLD, Nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; PDFF, Proton Density Fat Fraction; ASK-1, Apoptosis signal-regulating kinase 1; CCR-2, C-C chemokine receptor type 2; NAS, NAFLD Activity Score.
*Subgroup analysis of patients assigned to receive 120 mg elafibrinor (no significant difference was seen in the group receiving 80 mg compared to placebo).