Lipid-efficacy RCT · N Engl J Med 2022
OCEAN(a)-DOSE trial
Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease.
The bottom line
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.
Primary lipid endpoint metUS status: Investigational
At a glance
- Medicine
- Olpasiran (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks, subcutaneous)
- Compared with
- Matching placebo
- People
- 281
- Who took part
- Patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter
- Design
- randomized, double-blind, placebo-controlled, dose-finding trial
- Follow-up
- 36 weeks
- Main question
- Percent change in lipoprotein(a) concentration from baseline to week 36 (placebo-adjusted mean percent change)
Main result
Placebo-adjusted mean percent changes of -70.5% with the 10-mg dose, -97.4% with the 75-mg dose, -101.1% with the 225-mg dose administered every 12 weeks, and -100.5% with the 225-mg dose administered every 24 weeks (P<0.001 for all comparisons with baseline)
Effect on LDL cholesterol
Median LDL-C at baseline was 67.5 mg per deciliter; no post-treatment LDL-C change reported
Other results
Not reported; longer and larger trials will be necessary to determine the effect of olpasiran therapy on cardiovascular disease
Safety
The overall incidence of adverse events was similar across the trial groups. The most common olpasiran-related adverse events were injection-site reactions, primarily pain.
In the trial's own words
“At 36 weeks, the lipoprotein(a) concentration had increased by a mean of 3.6% in the placebo group, whereas olpasiran therapy had significantly and substantially reduced the lipoprotein(a) concentration in a dose-dependent manner, resulting in placebo-adjusted mean percent changes of -70.5% with the 10-mg dose, -97.4% with the 75-mg dose, -101.1% with the 225-mg dose administered every 12 weeks, and -100.5% with the 225-mg dose administered every 24 weeks (P<0.001 for all comparisons with baseline).”
Quoted from the abstract of N Engl J Med 2022, checked word for word against PubMed. PubMed 36342163 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Olpasiran, lepodisiran and zerlasiran
Common questions
What did the OCEAN(a)-DOSE trial find?
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.
Who was in OCEAN(a)-DOSE?
281 people. Patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter.
What was OCEAN(a)-DOSE's main result?
Placebo-adjusted mean percent changes of -70.5% with the 10-mg dose, -97.4% with the 75-mg dose, -101.1% with the 225-mg dose administered every 12 weeks, and -100.5% with the 225-mg dose administered every 24 weeks (P<0.001 for all comparisons with baseline)
How much did LDL cholesterol change in OCEAN(a)-DOSE?
Median LDL-C at baseline was 67.5 mg per deciliter; no post-treatment LDL-C change reported
Related trials
- Pelacarsen phase 2 (2020)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.
- 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.
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