Table 2.
Overview of the current pharmacological agents for the treatment of NAFLD/NASH.
| Drug | Mechanism/target | Clinical improvements |
Current phase | ||||
|---|---|---|---|---|---|---|---|
| IR | Steatosis | NASH | Apoptosis | Fibrosis | |||
|
Therapies targeting insulin resistance and de novo lipogenesis | |||||||
| Obeticholic acid | FXR agonist | ● | ● | ● | III | ||
| Cilofexor (GS-9674) | FXR agonist | ● | II | ||||
| Tropifexor | Non-steroidal FXR agonist | ● | ● | II | |||
| Firsocostat (GS-0976) | ACC inhibitor | ● | ● | ● | II | ||
| Cilofexor + firsocostat | FXR agonist + ACC inhibitor | ● | ● | ● | ● | II | |
| TVB-2640 | FASn inhibitor | ● | II | ||||
| Aramchol | SCD1 inhibitor | ● | ● | III | |||
| Pradigastat | DGAT1 inhibitor | ● | II | ||||
| Elafibranor | PPARα/β agonist | ● | III1 | ||||
| Seladelpar (MBX-8025) | PPARδ agonist | ● | II2 | ||||
| Saroglitazar | PPARα/γ agonist | ● | II | ||||
| 25-hydroxycholesterol3-sulfate | LXR inhibitor | ● | ● | ● | I | ||
| Pegbelfermin (BMS-986036) | FGF21 analogue | ● | II | ||||
| NGM-282 | FGF19 analogue | ● | ● | ● | II | ||
| Ursodeoxycholic acid (UDCA) | Bile acid | ● | ● | II | |||
|
Therapies targeting apoptosis | |||||||
| Emricasan | Caspase inhibitor | ● | ● | ● | II3 | ||
| Selonsertib | ASK1 inhibitor | ● | ● | ● | III4 | ||
| Simtuzumab | Antibody against LOXL2 | ● | ● | ● | II | ||
| Selonsertib + simtuzumab | ● | ● | ● | II | |||
|
Therapies targeting fibrosis | |||||||
| Cenicriviroc | CCR2/5 antagonist | ● | ● | III5 | |||
| Belapectin (GR-MD-02) | Galactin-3 inhibitor | ● | ● | II | |||
ACC, acetyl-coA carboxylase; ASK1, apoptosis signal-regulating kinase 1; CCR2/5, C-C chemokine receptor type 2/5; DGAT1, diacylglycerol acyltransferase 1; FASn, fatty acid synthase; FGF21, fibroblast growth factor 21; FXR, farnesoid X receptor; IR, insulin resistance; LOXL2, lysyl oxidase-like 2; LXR, liver X receptor; PPAR, peroxisome proliferative activated receptor; SCD1, steroyl-coA desaturase 1.
Phase III has been stopped because elafibranor failed to reach the primary endpoint
Phase IIb trial had to be halted after the appearance of liver cell damage and signs of inflammation in some participants.
Phase II trials of emricasan failed to reach their primary endpoints.
Phase III trial of selonsertib failed to reach its primary endpoint.
Phase III trial of cenicriviroc was terminated early due to a lack of efficacy.