Outcomes trials first (the four that will decide the field), then the phase 2 and 3 studies behind them. Facts from ClinicalTrials.gov and the publications; dates are the registry's, checked at each build. See also the agents and the timeline.
| Trial | Agent | N | Status | Registry |
|---|---|---|---|---|
| Lp(a)HORIZON | Pelacarsen | 8,323 | Completed, results awaited | |
| OCEAN(a)-Outcomes | Olpasiran | 7,297 | Ongoing, primary completion March 2028 | |
| ACCLAIM-Lp(a) | Lepodisiran | 17,300 | Ongoing, enrolment complete, primary completion March 2029 | |
| MOVE-Lp(a) (muvalaplin outcomes) | Muvalaplin | 10,450 | Recruiting, primary completion March 2031 | |
| ALPACAR (zerlasiran phase 2) | Zerlasiran | 178 | Completed, published JAMA 2024; phase 3 awaits a partner | |
| KRAKEN (muvalaplin phase 2) | Muvalaplin | 233 | Completed, published JAMA 2025 | |
| ALPACA (lepodisiran phase 2) | Lepodisiran | 320 | Completed, published NEJM 2025 | |
| Lp(a)FRONTIERS APHERESIS | Pelacarsen | Completed, published July 2026 | ||
| OCEAN(a)-DOSE | Olpasiran | 281 | Completed, published NEJM 2022 (extension JACC 2024) | |
| Pelacarsen phase 2 (AKCEA-APO(a)-LRx) | Pelacarsen | 286 | Completed, published NEJM 2020 |
Completed, results awaited
The first cardiovascular outcomes trial of any Lp(a)-lowering therapy: 8,323 patients with prior myocardial infarction, ischaemic stroke or symptomatic peripheral artery disease and Lp(a) of 70 mg/dL (about 149 nmol/L) or more, randomised to monthly subcutaneous pelacarsen 80 mg or placebo, event-driven to 993 adjudicated MACE. Primary completion was set for 30 June 2026; Novartis and Ionis guided the readout to…
Ongoing, primary completion March 2028
7,297 patients with established atherosclerotic cardiovascular disease and Lp(a) of 200 nmol/L or more, randomised to olpasiran 75 mg subcutaneously every 12 weeks or placebo; primary endpoint time to CHD death, MI or urgent coronary revascularisation. Started December 2022; ClinicalTrials.gov gives primary completion as 31 March 2028, and Amgen has pointed to a readout in 2026 to 2027.
Ongoing, enrolment complete, primary completion March 2029
The largest Lp(a) outcomes trial: 17,300 adults with elevated Lp(a) who have established ASCVD or are at risk of a first cardiovascular event, randomised to lepodisiran (an extended-duration siRNA given by subcutaneous injection about every six months) or placebo. Started March 2024, no longer recruiting, primary completion expected March 2029.
Recruiting, primary completion March 2031
The first outcomes trial of an oral Lp(a)-lowering drug: 10,450 adults with elevated Lp(a) who have had a prior ASCVD event or are at risk of a first one, randomised to daily muvalaplin or placebo; MACE endpoint. Started September 2025, primary completion expected March 2031.
Completed, published JAMA 2024; phase 3 awaits a partner
178 patients with stable ASCVD and Lp(a) of 125 nmol/L or more (median 213) at 26 sites in Europe and South Africa: zerlasiran 450 mg every 24 weeks, 300 mg every 16 weeks or 300 mg every 24 weeks lowered time-averaged Lp(a) to week 36 by 85.6, 82.8 and 81.3 percent, with median week-36 reductions of 90 to 96 percent and only mild injection-site reactions. Silence Therapeutics has said it will start the phase 3…
Completed, published JAMA 2025
233 participants with Lp(a) of 175 nmol/L or more and ASCVD, diabetes or FH took muvalaplin 10, 60 or 240 mg daily or placebo for 12 weeks: placebo-adjusted reductions of 47.6, 81.7 and 85.8 percent on an intact Lp(a) assay and 40.4, 70.0 and 68.9 percent on a traditional apo(a)-based assay; apoB fell up to 16 percent; hs-CRP unchanged; no safety concerns. Presented at AHA 2024.
Completed, published NEJM 2025
320 participants with median Lp(a) of 254 nmol/L: lepodisiran 400 mg at baseline and day 180 lowered time-averaged Lp(a) by 93.9 percent from day 60 to 180 (placebo-adjusted) and by 94.8 percent from day 30 to 360; a single 400 mg dose held 88.5 percent over the year. Mild injection-site reactions in up to 12 percent, no drug-related serious adverse events. Presented at ACC.25.
Completed, published July 2026
51 German patients with Lp(a) above 60 mg/dL and established cardiovascular disease on weekly lipoprotein apheresis were randomised to pelacarsen 80 mg or placebo every 4 weeks for 52 weeks; apheresis was performed only if Lp(a) stayed above 60 mg/dL. Pelacarsen reduced the rate of apheresis sessions from 0.93 to 0.16 of the weekly schedule, with a median 6.1 weeks to apheresis avoidance and a 72 percent…
Completed, published NEJM 2022 (extension JACC 2024)
281 patients with ASCVD and Lp(a) above 150 nmol/L (median 260) received olpasiran 10, 75 or 225 mg every 12 weeks, 225 mg every 24 weeks or placebo: placebo-adjusted Lp(a) reductions at week 36 of 70.5, 97.4, 101.1 and 100.5 percent, injection-site reactions the main adverse event. Off treatment, Lp(a) was still 40 to 50 percent below baseline nearly a year after the last dose.
Completed, published NEJM 2020
286 patients with established cardiovascular disease and Lp(a) of 60 mg/dL (150 nmol/L) or more received the hepatocyte-directed antisense oligonucleotide for 6 to 12 months: mean reductions of 35 percent (20 mg every 4 weeks) to 80 percent (20 mg weekly) versus 6 percent on placebo, injection-site reactions the main adverse event. Selected the 80 mg monthly regimen for Lp(a)HORIZON.