The PROMINENT trial of the selective peroxisome proliferator-activated receptor α (PPARα) agonist, pemafibrate, has been halted early. This follows a planned interim analysis by the Data Safety Monitoring Board (DSMB) which concluded that the study was unlikely to meet its primary endpoint (a composite of non-fatal myocardial infarction, non-fatal ischemic stroke, coronary revascularisation and cardiovascular death). Notable safety concerns were not raised, and it is planned to investigate the potential of pemafibrate in new therapeutic areas, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), based on encouraging data from the analysis of PROMINENT results.
Earlier in the ACC congress, Dr Aruna Pradhan (Harvard Medical School, Boston, USA) had reported that endpoint accrual for PROMINENT was ahead of schedule and due to complete by the end of 2022. The study of 10,497 patients with type 2 diabetes, triglycerides (TGs) of 200-499 mg/dL and HDL <40 mg/dL, on moderate- to high-intensity statin or LDL-C control, was events-driven, with 1,304 events required in order to test the composite primary endpoint of MI, ischaemic stroke, CV death or coronary revascularisation.
Pradhan also presented recently published results of a Phase 2 study of pemafibrate in statin-treated patients with hypertriglyceridaemia in Europe, with or without established CV disease and/or type 2 diabetes.1
Pemafibrate 0.05 mg twice a day, 0.1 mg twice a day, 0.2 mg twice a day, 0.1 mg once daily, 0.2 mg once daily, or 0.4 mg once daily significantly reduced TG at all doses (adjusted p value <0.001), with the greatest placebo-corrected reduction from baseline to week 12 in the 0.2 mg twice a day treatment group (54.4%). Reductions in non-HDL- cholesterol did not reach statistical significance. TG reductions were associated with improvements in other markers for TG-rich lipoprotein metabolism, including reductions in apoB48, apoCIII, and remnant cholesterol and an increase in HDL-C levels. Significant increases in LDL-C ranging from 9.2-20.5% were observed at all doses except 0.05 mg twice a day, while apoB100 was unchanged.
Reference
- Ginsberg H, Hounslow NJ, Senko Y et al. Efficacy and Safety of K-877 (Pemafibrate), a Selective PPARα Modulator, in European Patients on Statin Therapy. Diabetes Care 2022;45(4):898–908