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
THOUSAND OAKS,
Calif. , Nov. 6, 2022 /PRNewswire/ -- 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
nmol/L) 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."
About Lp(a)
Lp(a) is genetically determined3-5 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
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 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.
About Amgen
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
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References
1. O'Donoghue ML, et al. Am Heart J. 2022;251:61-9.
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.
3. Wilson DP, et al. Clin Lipidol. 2019;13(3):374-92.
4. Reyes-Soffer G, et al. Arterioscler Thromb Vasc Biol.
2022;42(1):e48-e60.
5. Tsimikas S, et al. J Am Coll Cardiol. 2018;71(2): 177–192.
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Jessica Akopyan, 805-440-5721
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Michael Strapazon, 805-313-5553
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Arvind Sood, 805-573-4142
(investors)
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