Phase II OCEAN(a)-DOSE trial results in adults with elevated lipoprotein levels and atherosclerotic cardiovascular disease

The study was designed to assess safety, tolerability and optimal dose of olpasiran in adults with established ASCVD to reduce Lp(a). These data were presented during the Nov. 6 Late-Breaking Science Session of the American Heart Association (AHA) Scientific Sessions 2022 in Chicago, Illinois, and simultaneously published in the New England Journal of Medicine.

OCEAN(a)-DOSE is a multicenter, randomized, double-blind, placebo-controlled dose-finding study of olpasiran in 281 patients with established ASCVD and Lp(a) levels >150 nmol/L. Patients were randomized to one of four doses of olpasiran (10 mg Q12 weeks, 75 mg Q12 weeks, 225 mg Q12 weeks or 225 mg Q24 weeks) or placebo, given subcutaneously. Across cohorts, the median baseline Lp(a) concentration was 260.3 nmol/L. Patients who received 75 mg or higher every 12 weeks had a 95% or greater reduction in Lp(a) compared to placebo at week 36. At these doses (75 mg or higher), more than 98% of patients achieved an Lp(a) level of 125 nmol/L or less at week 36. Overall, the rates of adverse events were similar in the olpasiran and placebo arms. The most common treatment-related adverse events were injection site reactions, primarily pain.

"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,"⁵ said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Our Phase II 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 III clinical trials, which we expect to begin enrolling in December 2022."

At week 36, Lp(a) increased by a mean of 3.6% in the placebo arm, whereas there were substantial reductions of Lp(a) levels in all of the olpasiran arms. 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.

About Lp(a): Lp(a) is genetically determined and a presumed independent risk factor for cardiovascular disease (CVD). Although an agreed upon threshold for elevated Lp(a) is not firmly established, approximately 20% of adults have Lp(a) >125 nmol/L (or approximately 50 mg/dL).3 Evidence has emerged from pathophysiological, epidemiologic, and genetic studies on the potential role of elevated Lp(a) in contributing to myocardial infarction, stroke, and peripheral arterial disease.

About OCEAN(a): The OCEAN(a) (Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction) clinical program for Amgen's investigational olpasiran is designed to treat patients with atherosclerotic cardiovascular disease (ASCVD) and elevated Lp(a) levels to reduce the risk of cardiovascular events. The OCEAN(a)-DOSE trial is a multicenter, randomized, double-blind, placebo-controlled dose-finding Phase II study in 281 patients with ASCVD and Lp(a) >150 nmol/L. Patients were randomly assigned to one of four active subcutaneous doses of olpasiran (10 mg Q12 weeks, 75 mg Q12 weeks, 225 mg Q12 weeks or 225 mg Q24 weeks) or placebo. The primary endpoint is percent change from baseline in Lp(a) at 36 weeks. A secondary endpoint is percent change from baseline in Lp(a) at 48 weeks. A prespecified exploratory endpoint was the percent change in Lp(a) from baseline at each scheduled visit for the 225 mg Q24 week dose group.

See-" Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease." M.L. O’Donoghue and Others 10.1056/NEJMoa2211023.