Lipid-efficacy RCT · N Engl J Med 2020
Pelacarsen phase 2 trial
Lipoprotein(a) Reduction in Persons with Cardiovascular Disease.
The bottom line
In patients with cardiovascular disease and elevated Lp(a), the antisense drug APO(a)-LRx (pelacarsen) lowered Lp(a) levels in a dose-dependent manner, with no significant safety signals versus placebo, though cardiovascular outcomes were not assessed in this trial.
Primary lipid endpoint metUS status: Investigational
At a glance
- Medicine
- Hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx (pelacarsen) at 20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week, subcutaneously
- Compared with
- Saline placebo subcutaneously
- People
- 286
- Who took part
- Patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter)
- Design
- randomized, double-blind, placebo-controlled, dose-ranging trial
- Follow-up
- 6 to 12 months
- Main question
- Percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in monthly-dose groups and week 27 in more frequent dose groups)
Main result
Mean percent decreases in lipoprotein(a) of 35% at 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001)
Effect on LDL cholesterol
''
Other results
''
Safety
There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions.
In the trial's own words
“Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001).”
Quoted from the abstract of N Engl J Med 2020, checked word for word against PubMed. PubMed 31893580 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Pelacarsen
Common questions
What did the Pelacarsen phase 2 trial find?
In patients with cardiovascular disease and elevated Lp(a), the antisense drug APO(a)-LRx (pelacarsen) lowered Lp(a) levels in a dose-dependent manner, with no significant safety signals versus placebo, though cardiovascular outcomes were not assessed in this trial.
Who was in Pelacarsen phase 2?
286 people. Patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter).
What was Pelacarsen phase 2's main result?
Mean percent decreases in lipoprotein(a) of 35% at 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001)
How much did LDL cholesterol change in Pelacarsen phase 2?
''
Related trials
- OCEAN(a)-DOSE (2022)Olpasiran markedly and dose-dependently lowered lipoprotein(a) levels in patients with established atherosclerotic cardiovascular disease and elevated Lp(a), with similar overall adverse event rates to placebo, but whether this translates into reduced cardiovascular events remains to be determined.
- ALPACA (zerlasiran phase 2) (2024)In patients with established atherosclerotic cardiovascular disease and very high Lp(a), zerlasiran safely lowered Lp(a) levels by more than 80% on average over 36 weeks compared with placebo.
- ALPACA (2025)Lepodisiran produced large, dose-dependent and durable reductions in serum lipoprotein(a) with generally mild injection-site reactions, but this trial did not assess cardiovascular outcomes.
- KRAKEN (2025)Oral muvalaplin produced large, dose-dependent reductions in lipoprotein(a) over 12 weeks with no safety or tolerability concerns, though whether this translates into fewer cardiovascular events is still unknown.
Get your LDL treated to a goal
Preval Health's protocols follow trials like this one. Licensed clinicians set your goal, prescribe and recheck until you reach it.
Get startedEducation only, not medical advice. Results describe the people in this trial and can differ for you. Talk with your clinician before starting or stopping any medicine. Back to all 106 trials.