Olpasiran cut Lp(a) levels by more than 95% in patients with atherosclerotic CVD
Click Here to Manage Email Alerts
CHICAGO — Olpasiran, a small interfering RNA agent directed to the liver, yielded substantial and sustained reductions in lipoprotein(a) concentrations among patients with established atherosclerotic CVD in the phase 2 OCEAN(a)-DOSE study.
“Olpasiran ... dosed at 75 mg or higher every 12 weeks reduces Lp(a) concentration by more than 95% in patients with established atherosclerotic cardiovascular disease,” Michelle L. O’Donoghue, MD, MPH, FAHA, cardiovascular medicine specialist and senior investigator of the TIMI Study Group at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, said during a presentation at the American Heart Association Scientific Sessions.
Source: Adobe Stock
Dose-dependent reductions
In this study, patients were randomly assigned to receive placebo or one of four doses of subcutaneous olpasiran (Amgen). Olpasiran reduced Lp(a) concentrations in a dose-dependent manner, the researchers reported. The primary endpoint, percent change in Lp(a) concentration from baseline to 36 weeks, was as follows:
- –70.5% with olpasiran 10 mg every 12 weeks;
- –97.4% with olpasiran 75 mg every 12 weeks;
- –101.1% with olpasiran 225 mg every 12 weeks;
- – 100.5% with olpasiran 225 mg every 24 weeks; and
- 3.6% increase with matching placebo
The P value for the primary endpoint was < .001 for all comparisons compared with baseline.
In other results, the percent of patients who achieved an Lp(a) concentration below 125 nmol/L was 66.7% with the 10 mg dose every 12 weeks, 100% with the 75 mg and 225 mg doses every 12 weeks and 98.1% with the 225 mg dose every 24 weeks, according to the results. No patients in the placebo group achieved that goal.
Adverse events were similar in the olpasiran and placebo groups. The most common treatment-related adverse events were injection-site and hypersensitivity reactions, which were mild and resolved without treatment, according to O’Donoghue.
“To date, the drug appears both safe and well tolerated,” O’Donoghue said during the late-breaking science presentation.
OCEAN(a)-DOSE was a randomized, double-blind, placebo-controlled, dose-finding, phase 2 trial. The 281 patients enrolled had established ASCVD and Lp(a) concentrations greater than 150 nmol/L. At baseline, the median Lp(a) concentration was 260.3 nmol/L and median LDL concentration was 67.5 mg/dL. Eighty-eight percent of patients were also on statin therapy, 52% on ezetimibe and 23% on a PCSK9 inhibitor at baseline. The mean age of those enrolled was 62 years, 32% were women and the majority were white.
The study was conducted at 34 sites in seven countries.
“These findings set the foundation for phase 3 testing scheduled to commence later this year,” O’Donoghue said.
‘Hope is in sight’
“Hope is in sight” for patients with elevated levels of Lp(a), Stephen J. Nicholls, MBBS, PhD, director of Monash Heart and professor at Monash University in Melbourne, Australia, said during a discussion of the trial.
Nicholls said there remain many unknowns about Lp(a), including whether lowering Lp(a) will reduce CV risk, how the presence of other factors such as inflammation influence risk, whether reducing it greatly will have long-term consequences, whether substantial reductions will increase the rate of diabetes; and whether there will be consequences to stopping therapy.
Nicholls said multiple trials may be needed to answer these unknown questions.
“As we move forward and the field is excited, and we have therapeutics in this space, it will be just as important for us to increase the testing of Lp(a) in clinical practice,” Nicholls said.
References:
- O’Donoghue ML, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2211023.
- Amgen presents new phase 2 data that show olpasiran delivers significant reduction in lipoprotein(a) levels. https://www.amgen.com/newsroom/press-releases/2022/11/amgen-presents-new-phase-2-data-that-show-olpasiran-delivers-significant-reduction-in-lipoproteina-levels. Published Nov. 6, 2022. Accessed Nov. 6, 2022.
Perspective
Back to Top
Dipti Itchhaporia, MD, MACC, FESC, FAHA
This trial was interesting. It looked at whether we can reduce Lp(a), which could ultimately lead to decreased CV events. The trial evaluated whether olpasiran could reduce Lp(a) and tested multiple doses to see which one is optimal. The 75-mg dose provided a more than 90% reduction in Lp(a) in patients with established CAD. There were no adverse events.
While this was a dosing trial and we have to wait for the phase 3 trial to see the effect on CV outcomes, this is an agent we need to keep an eye on in the future, because whether reduction of Lp(a) translates into reduced CV events is a very interesting question.
Director of disease management
Jeffrey M. Carlton Heart and Vascular Institute
Hoag Memorial Hospital, Newport Beach, California
Associate clinical professor of medicine
University of California, Irvine
Immediate past president, American College of Cardiology
Collapse
O’Donoghue ML, et al. LBS.05: Changing How We Prevent Cardiovascular and Renal Disease. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
Click Here to Manage Email Alerts