TABLE 2.
Main clinical outcomes of PPARα-related drugs for liver fibrosis
| Agent | Clinical Trial # (Phase) | Comments | Effects | Refs. | |||
|---|---|---|---|---|---|---|---|
| PPARa agonist | |||||||
| Bezafibrate | NCT01654731 (III) | In PBC patients (24 months): improved biochemical response, pruritus and liver stiffness. |
|
259 | |||
| NCT02701166 (III) | In PSC and PBC patients (21 days): improved pruritus |
|
260 | ||||
| NCT02937012 (III) | In PBC patients (3–12 months): improved cholestasis |
|
(261, 262) | ||||
| Fenofibrate | NCT02781584 (II) | In NASH patients (2 weeks): improved hypertriglyceridemia |
|
263 | |||
| NCT02354976 (II) | In NAFLD patients (12 weeks): reduced serum triglycerides |
|
264 | ||||
| NCT02891408 (I) | In NASH patients: completed, no results posted. | — | |||||
| NCT00575042 (II) | In PBC patients (48 weeks): biochemical improvement |
|
265 | ||||
| Pemafibrate (K-877) | NCT03350165 (II) | In NAFLD/NASH patients (72 weeks): reduced liver stiffness |
|
266, 267 | |||
| FGF21 mimetics | |||||||
| Pegbelfermin (BMS-986036) | NCT02413372 (II) | In NASH patients (16 weeks): reduced hepatic fat content and liver transaminases, increased serum levels of adiponectin and improved lipid profde. |
|
268 | |||
| NCT03400163 (II) | In NASH patients: completed, no results posted. | — | |||||
| NCT03445208 (I) | In NASH patients: completed, no results posted. | — | |||||
| NCT03486899 (II) NCT03486912 (II) | In NASH patients (24, 48 weeks): improved fibrosis without NASH worsening. |
|
269 | ||||
| NCT03674476 (I) | In NASH patients: completed, no results posted. | — | |||||
| Efruxifermin | NCT03976401 (Ila) | In NASH patients (16 weeks): improved hepatic fat content, NASH, and fibrosis. |
|
270 | |||
| PPARα/γ agonist | |||||||
| Elafibranor | NCT03124108 (11) | In PBC patients (12 weeks): improved serum biochemical response and pruritus. |
|
271 | |||
| NCT04526665(III) | In PBC patients: No results posted. | — | |||||
| NCT01694849 (II) | In NASH patients (52 weeks): resolved NASH (F0-F3) without fibrosis worsening, improved cardiometabolic risk profile. |
|
272 | ||||
| NCT02704403 (III) | In NASH patients (72 weeks): terminated for not achieving NASH resolution without worsening fibrosis |
|
|||||
| PPARα/γ agonist | |||||||
| Saroglitazar | NCT03061721 (II) | In NASH patients (16 weeks): improved ALT, liver fat content, insulin resistance and atherogenic disorders. Side effects: weight gain |
|
273 | |||
| NCT03112681 (II) | In PBC patients (16 weeks): improved serum ALP (primary endpoint) and γGT levels Side effects: increase ALT in some patients |
|
(274, 275) | ||||
| NASH (II) | Very small study demonstrating improved serum lipid and lipoprotein profiles; improvements in hepatocyte ballooning and steatosis; NASH resolution and fibrosis improvement were observed |
|
(13) | ||||
| NCT03863574 (II) | In NASH patients: completed, no results posted. | — | |||||
| Pan-PPAR agonist | |||||||
| Lanifibranor | NCT03008070 (II) | In NASH and F0-F3 fibrosis patients (24 weeks): improved biopsy-confirmed NASH, liver injury, inflammation, and fibrosis. |
|
276, 277 | |||
| NCT03459079 (II) | In NASH patients: No results posted. | — | 225 | ||||
| NCT04849728(III) | In NASH and F0-F3 fibrosis patients: No results posted. | — | |||||
: positive effect on steatosis (), inflammation (), or fibrosis ().
: neutral or non-available effect on steatosis (), inflammation (), or fibrosis ().
Abbreviations: ALP, alkaline phosphatase; PPRE, peroxisome proliferators response elements; PPARα, peroxisome proliferator-activated receptor alpha; Refs., references.