Drug target | Drug name | Study participants | Main Results | References |
---|---|---|---|---|
ACC inhibitor | GS-0976 | 10 patients with NASH and 10 healthy volunteers | Reduce hepatic DNL by 22%, MRI-PDFF LFC by 6.6%, MRE liver stiffness by 0.3Kpa, serum ALT by 44U/L after 12Â weeks. Decrease MRI-PDFF liver lipid accumulation more than 30% in 70% of participants | [69] |
126 patients with more than 8% of LFC by MRI-PDFF and more than 2.5 kPa of stiffness by MRE or biopsy-proven NASH and F1-F3 fibrosis | Decrease MRI-PDFF LFC by more than 30% in 23–48% participants in a dose-dependent mode after 12 weeks. Increase serum TG in 11–13% of participants | [70] | ||
PF05221304 | 305 overweight/obese patients with NAFLD (more than 8% LFC by MRI-PDFF) and with more than 2 of 5 risk factors of NAFLD | Reduce MRI-PDFF LFC by 50–65% with PF-05221304 dose ≥ 10 mg QD after 16 weeks | [83] | |
FAS inhibitor | Denifanstat (TVB-2640) | 12 obese men with certain metabolic abnormalities | Reduce fasting DNL by up to 90%, and ALT by 15.8% after 10Â days | [73] |
99 patients with more than 8% LFC by MRI-PDFF and liver fibrosis of more than 2.5Â kPa by MRE or liver biopsy | Reduce LFC by 9.6% in 25Â mg group and 28.1% in 50Â mg group after 12Â weeks | [74] | ||
SCD1 inhibitor | Aramchol | 247 patients with NASH proved by biopsy results | Achieve NASH resolution in 16.7% of participants and fibrosis improvement without worsening NASH in 29.5% after 52-week treatment. Reduce ALT by 29.1U/L. Liver fat by MRS was not significantly reduced | [77] |
50 patients with HIV-associated NAFLD (more than 5% LFC by MRI-PDFF) | Do not reduce MRI-PDFF LFC or stiffness by MRE and VCTE after 12Â weeks | [78] | ||
DGAT2 inhibitor | PF-06427878 | 24 healthy participants in NCT02855177 and 39 healthy participants in NCT 02391623 | Reduce MRI-PDFF LFC and serum ALT, AST, alkaline phosphatase and total bilirubin in healthy adults after 14Â days | [80] |
IONIS-DGAT2Rx | 44 patients with BMI of 27-39 kg/m2, HbA1c of 7.3–9.5% and LFC by MRI-PDFF ≥ 10% | Reduce 5.2% LFC by MRI-PDFF after 13-week treatment | [81] | |
ACC/DGAT2 inhibitor | PF-05221304 and PF-06865571 | 99 overweight patients with metabolic syndrome and/or T2DM and more than 5% LFC by MRI-PDFF | Reduce 44.6% LFC by MRI-PDFF and serum TG after 6Â weeks | [83] |