Table 5.
Emerging Therapies for Hypertriglyceridemia
| Mechanism of Action | Trial | Trial Description | |
|---|---|---|---|
| SPPARM-α | |||
| Pemafibrate (Kowa Research Institute) | Selective PPAR-α modulator | PROMINENT (NCT03071692) (159) | RCT evaluating the efficacy of Pemafibrate vs placebo in reducing incidence of adverse CV events in ∼10,000 participants |
| Inclusion criteria: participants with T2DM and fasting TG ≥200 mg/dL and <500 mg/dL and HDL-C ≤40 mg/dL | |||
| OM3FAs | |||
| VASCEPA (icosapent ethyl) also known as AMR101 (Amarin Pharma) | Highly purified ethyl ester of EPA | REDUCE-IT (NCT01492361) (159) | RCT evaluating the efficacy of AMR101 vs placebo in reducing incident CV events in ∼8000 participants |
| Treatment dose: 4 g/d | Inclusion criteria: individuals with established CVD or at high risk with hypertriglyceridemia and receiving statin therapy | ||
| Epanova (AstraZeneca) | Omega-3 carboxylic acids | STRENGTH (NCT02104817) (160) | RCT evaluating the efficacy of Epanova vs corn oil in reducing MACE in ∼13,000 participants |
| Inclusion criteria: patients at high risk for future CV events on stable diet and statin therapy with LDL-C <100 mg/dL and TG level ≥180 mg/dL and <500 mg/dL and HDL-C <42 mg/dL for men or HDL-C <47 mg/dL for women | |||
| Omacor | Marine OM3FAs (465 mg of EPA and 375 mg of DHA) | VITAL (NCT01169259) (161) | RCT in 25,871 participants evaluating daily dietary supplementation of 2000 units of vitamin D3 or OM3FAs for reducing the risk of developing cancer, heart disease, and stroke |
| Treatment dose: 1 capsule/d (840 mg of marine OM3FA) | |||
| Icosabutate (162) | Potent, synthetically modified EPA molecule | No phase 3 outcomes trials underway | N/A |
| ApoCIII inhibitor | |||
| Volanesorsen | Antisense apoCIII inhibitor | COMPASS (NCT02300233) (160) | RCT evaluating the efficacy of volanesorsen vs placebo given for 52 wk in reducing fasting TG levels |
| Inclusion criteria: fasting TG level ≥500 mg/dL | |||
| Antisense apoCIII inhibitor | APPROACH (NCT02211209) (161) | RCT evaluating the efficacy of volanesorsen vs placebo in reducing fasting TG levels in patients with FCS | |
| Inclusion criteria: FCS with fasting TG level ≥750 mg/dL (8.4 mmol/L) at screening | |||
| ANGPTL3 inhibition | |||
| Evinacumab (REGN1500; Regeneron) (124) | Human monoclonal antibody against ANGPTL3 | No ongoing CV outcomes trials | N/A |
| IONIS-ANGPTLRX; Ionis Pharmaceuticals (163) | Antisense oligonucleotides targeting hepatic ANGPTL3 mRNA | No ongoing CV outcomes trials | N/A |
Abbreviations: ANGPTL, angiopoietin-like proteins; APPROACH, Study of Volanesorsen (formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome; COMPASS, Apolipoprotein C-III Inhibition With Volanesorsen in Patients With Hypertriglyceridemia; FCS, familial chylomicronemia syndrome; MACE, major adverse cardiac event; N/A, not applicable; PPAR, peroxisome proliferator–activated receptor; PROMINENT, Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Diabetic Patients; REDUCE-IT, Reduction of Cardiovascular Events With EPA–Intervention Trial; STRENGTH, Statin Residual Risk Reduction With Epanova in High CV Risk Patients With Hypertriglyceridemia; VITAL, Vitamin D and Omega-3 Trial.