Treatment With Olpasiran Significantly Lowers Lipoprotein(A) Levels

Treatment with olpasiran (Amgen) significantly lowered elevated lipoprotein(a) (Lp[a]) levels in adults with a history of atherosclerotic cardiovascular disease (ASCVD), according to data from the phase 2 OCEAN(a)-DOSE study presented at the recent American Heart Association (AHA) Scientific Sessions 2022 and published in the New England Journal of Medicine.

OCEAN(a)-DOSE is a randomized, placebo-controlled dose-finding study of olpasiran in 281 patients with established ASCVD and Lp(a) levels >150 nmol/L. Patients were randomized to 1 of 4 doses—olpasiran at 10 mg Q12 weeks, 75 mg Q12 weeks, 225 mg Q12 weeks or 225 mg Q24 weeks—or placebo, administered subcutaneously. The study evaluated the safety, tolerability, and optimal dosing for olpasiran in adults with established ASCVD to lower Lp(a).

Lp(a) is an independent risk factor for cardiovascular disease. The median baseline Lp(a) concentration was 260.3 nmol/L throughout the treatment groups.

Patients administered 75 mg or higher every 12 weeks had a 95% or greater reduction in Lp(a) compared to placebo at week 36. For these doses, more than 98% of patients achieved an Lp(a) level of 125 nmol/L or less at week 36.

"Epidemiological research has shown us that Lp(a) is an independent risk factor and is primarily genetically determined. It has been estimated that up to 20% of people worldwide are living with elevated levels, which are linked to a higher risk for heart disease, stroke and the potential significant burden on patients with cardiovascular disease," said David M. Reese, MD, executive vice president of Research and Development at Amgen, in a press release. "Our phase 2 data for olpasiran presented at AHA continue to demonstrate a significant reduction in Lp(a) and provide strong evidence supporting its potential for patients with ASCVD. We look forward to studying this treatment further in phase 3 clinical trials, which we expect to begin enrolling in December 2022."

At week 36 of the study, Lp(a) increased by a mean of 3.6% in the placebo cohort compared with substantial reductions of Lp(a) levels across all the olpasiran arms. The placebo-adjusted mean percent reductions were 70.5% for 10 mg every 12 weeks, 97.4% for 75 mg every 12 weeks, 101.1% for 225 mg every 12 weeks and 100.5% for 225 mg every 24 weeks.

Rates of adverse events (AEs) were similar in the olpasiran and placebo arms, with the most common treatment-related AEs being injection site reactions, or primarily pain.

"Currently, there are no approved medicines that can consistently achieve marked or sustained reductions in Lp(a) concentration," said Michelle L. O'Donoghue MD, MPH, senior investigator, TIMI Study Group at Brigham and Women's Hospital and OCEAN(a)-DOSE trial Global Principal Investigator, in a press release. "RNA interference with olpasiran is a promising treatment approach that led to a profound and sustained reduction in Lp(a) concentration in this phase 2 study."

REFERENCE

AMGEN presents new phase 2 data that show olpasiran delivers significant reduction in lipoprotein(a) levels. Amgen. November 6, 2022. Accessed November 7, 2022. https://wwwext.amgen.com/newsroom/press-releases/2022/11/amgen-presents-new-phase-2-data-that-show-olpasiran-delivers-significant-reduction-in-lipoproteina-levels