TABLE 1.
Drugs with ongoing or upcoming phase 3 and 4 clinical trials for NAFLD/NASH.
| Drug name | Targets and mechanism | Trial identifiers | Indication | Aim | Starting year | Phase and status | Sponsor |
|---|---|---|---|---|---|---|---|
| Belapectin | Galectin‐3 (Gal‐3) inhibitor | NAVIGATE (NCT04365868) | Patients with NASH cirrhosis and clinical signs of portal hypertension but without oesophageal varices at baseline | Evaluating the efficacy and safety of belapectin for the prevention of esophageal varices in NASH cirrhosis | 2020 | Phase 2b/3 | Galectin Therapeutics Inc. |
| Dulaglutide | GLP‐1R agonist | REALIST (NCT03648554) | T2DM with NASH | Researching an effect of GLP‐1 agonist on liver steatosis | 2019 | Phase 4 | Central Hospital, Nancy, France |
| Empagliflozin | SLGT2 inhibitor | NCT04642261 | NAFLD without DM | Effect of empagliflozin on liver fat in non‐diabetic patients | 2021 | Phase 4 | The University of Hong Kong |
| Erugliflozin | SGLT2 inhibitor | Ertu‐NASH (NCT05644717) | T2DM with NAFLD/NASH | Effect of erugliflozin on liver fat, liver fibrosis and glycemic control in type II DM patients with NASH/NAFLD | 2022 | Phase 4 | Getz Pharma |
| Lanifibranor (IVA337) | panPPAR agonist | NATiV3 (NCT04849728) | NASH and liver fibrosis histological stage F2 or F3 | Evaluating efficacy and safety of lanifibranor followed by an active treatment extension in adult patients with NASH and fibrosis stages F2 and F3 | 2021 | Phase 3 | Inventiva Pharma |
| MSDC‐0602K | Thiazolidinedione (TZD) insulin sensitizers | NCT03970031 | Subjects with pre‐T2DM or T2DM and evidence of NAFLD/NASH | Assess glycemic control and cardiovascular outcomes in patients with Pre‐T2D or T2D and NAFLD/NASH | 2022 | Phase 3 | Cirius Therapeutics, Inc. |
| Resmetirom (MGL‐3196) a | Selective THRβ agonist | MAESTRO‐NAFLD1 (NCT04197479) | NAFLD | Evaluate safety and biomarkers of resmetirom in NAFLD | 2019 | Phase 3 (completed) | Madrigal pharmaceuticals, Inc. |
| MAESTRO‐NASH (NCT03900429) | Patients with NASH and fibrosis | Evaluate the efficacy and safety of MGL‐3196 (resmetirom) in patients with NASH and fibrosis | 2019 | Phase 3 (completed) | |||
| MAESTRO‐NAFLD‐OLE (NCT04951219) | NAFLD | Evaluate safety and biomarkers of resmetirom in patients with NAFLD | 2021 | Phase 3 | |||
| MAESTRO‐NASH‐OUTCOMES (NCT05500222) | Patients with well‐compensated NASH cirrhosis | Evaluate the effect of resmetirom on clinical outcomes in patients with well‐compensated NASH cirrhosis | 2022 | Phase 3 | |||
| Saroglitazar | Dual PPAR agonist (a PPAR‐α/γ agonist) | NCT05872269 | NAFLD with comorbidities (either obesity, T2DM, dyslipidemia or metabolic syndrome) | Evaluate the safety and effectiveness of saroglitazar 4 mg in patients with NAFLD with comorbidities | 2023 | Phase 4 | Zydus Lifesciences Limited |
| Semaglutide | GLP‐1R agonist | ESSENCE (NCT04822181) | NASH | Study on whether semaglutide works in people with non‐alcoholic steatohepatitis | 2021 | Phase 4 | Novo Nordisk A/S |
Abbreviations: GLP‐1R, glucagon‐like peptide‐1 receptor; NAFLD, non‐alcoholic fatty liver disease; NASH, non‐alcoholic steatohepatitis; PPAR, peroxisome proliferators‐activated receptor; SGLT2, sodium‐glucose cotransporter‐2; T2DM, type 2 diabetes mellitus; THRβ, thyroid hormone receptor‐β agonist.
a
Resmetirom (MGL‐3196) has met the aforementioned endpoints in a Phase 3 clinical trial (interim analysis), which showed statistically significant benefits on fibrosis regression as well as NASH resolution, along with several other markers of efficacy, and a favourable safety and tolerability profile.