Table 4.
Ongoing trials and future perspective
| Target | Clinical trial | Mechanism of action | Molecules | Population | Phase | Endpoint | Results/expected results |
|---|---|---|---|---|---|---|---|
| LDL-C | CLEAR Harmony [36] | ACL-inhibitor | Bempedoic acid | 1950 high CV risk patients | 3 | Safety, tolerability | 2018 |
| MBX-8025 [37] | Selective PPARδ | MBX-8025 | 13 patients with HoFH | 2 | Effect on LDL-C | Full results – early 2017 | |
| HDL-C | REVEAL [31] | CETP inhibitors | Anacetrapib | 30,624 patients with a history of MI stroke or PAD | 3 | Major coronary events (defined as coronary death, MI or coronary revascularisation) | Early 2017 |
| MILANO-PILOT [38] | Apo A‑I mimetics | MDCO-216 | 120 ACS patients | 2 | Change in PAV | No significant effect | |
| CARAT [39] | Apo A‑I mimetics | CER-001 | 301 ACS patients | 2 | Change in PAV | Early 2017 | |
| AEGIS [40] | Apo A‑I mimetics | CSL-112 | 1258 ACS patients | 2b | Safety, tolerability, PK | Well tolerated and safe | |
| Triglycerides | IONIS ANGPTL3-LRx [41] | Inhibition of LPL activity | IONIS ANGPTL3-LRx | 61 healthy volunteers | 1–2 | Safety, tolerability, PK/PD | June 2017 |
| L(p) a | IONIS-APO(a)-Rx [43] | Antisense oligonucleotide targeting hepatic apo(a) mRNA | IONIS-APO(a)-LRx | 64 participants with high Lp(a) levels | 2 | %change in Lp(a) | −71.6% |
| IONIS-APO(a)-LRx [43] | Ligand-conjugated antisense oligonucleotide | IONIS-APO(a)-LRx | 58 healthy volunteers | 1/2 | %change in fasting Lp(a) | −92% |
LDL-C low-density lipoprotein cholesterol, ATP adenosine triphosphate, ACL-inhibitor ATP-Citrate Lyase inhibitor, PPARδ peroxisome proliferator-activated receptor delta, HoFH homozygous familiar hypercholesterolemia, CV cardiovascular, ACS acute coronary syndrome, PAV percentage atheroma volume, PK pharmacokinetics, PD pharmacodynamics, ApoA-I apolipoprotein A-I, MI myocardial infarction, PAD peripheral arterial disease, CETP cholesteryl ester transfer protein, LPL lipoprotein lipase, Lp(a) lipoprotein (a), mRNA messenger RNA, MILANO-PILOT MDCO-216 Infusions Leading to Changes in Atherosclerosis: A Novel Therapy in Development to Improve Cardiovascular Outcomes – Proof of Concept Intravascular Ultrasound (IVUS), Lipids, and Other Surrogate Biomarkers Trial, CARAT CER-001 Atherosclerosis Regression ACS Trial, AEGIS The ApoA-I Event Reduction in Ischemic Syndromes I, REVEAL Randomized EValuation of the Effects of Anacetrapib though Lipid-modification, IONIS ANGPTL3-LRx IONIS Angiopoietin-like 3‑linear RNAx