AMGEN PRESENTS NEW PHASE 2 DATA THAT SHOW OLPASIRAN DELIVERS SIGNIFICANT REDUCTION IN LIPOPROTEIN LEVELS

Olpasiran Reduced Lipoprotein(a) Levels by More Than 95% in Patients With Established ASCVD

Amgen is Initiating a Phase 3 Cardiovascular Outcomes Trial Based on These Results

Data Simultaneously Published in the New England Journal of Medicine

Amgen (NASDAQ:AMGN) today presented end-of-treatment data from its Phase 2 OCEAN(a)-DOSE study of investigational olpasiran (formerly AMG 890) in adults with elevated lipoprotein(a) [Lp(a)] levels (>150 nmolL) and a history of atherosclerotic cardiovascular disease (ASCVD). The study was designed to assess safety, tolerability and optimal dose of olpasiran in adults with established ASCVD to reduce Lp(a). 1 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. ² 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. ² 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. ²

"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 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, 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 . ²

"Currently, there are no approved medicines that can consistently achieve marked or sustained reductions in Lp(a) concentration," said Michelle L. O'Donoghue M.D ., MPH, Senior Investigator, TIMI Study Group at Brigham and Women's Hospital and OCEAN(a)-DOSE trial Global Principal Investigator. "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."

Lp(a) is genetically determined ^3-5 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. ⁵

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 2 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.

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's.

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2. O'Donoghue, Michelle (2022, November 5-7 ). Reduction of Lipoprotein(a) With Small Interfering RNA: The Results of the Ocean(a)-DOSE Trial (OCEAN(a) DOSE) [Conference Presentation]. American Heart Association Scientific Sessions, Chicago, Illinois .
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