THOUSAND OAKS, Calif. and
SOUTH SAN FRANCISCO, Calif.,
Nov. 30, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) and Cytokinetics, Inc. (NASDAQ:CYTK) today announced
The Lancet published results from a Phase 2 clinical trial
evaluating omecamtiv mecarbil in patients with chronic heart
failure. The COSMIC-HF (Chronic Oral Study of Myosin Activation to
Increase Contractility in Heart Failure) trial met its primary
pharmacokinetic objective and showed statistically significant
improvements in all pre-specified secondary measures of cardiac
function in the treatment group receiving pharmacokinetic-based
dose titration. The results were initially presented as a
Late-Breaking Clinical Trial at the American Heart Association
(AHA) Scientific Sessions 2015.1
"Data from COSMIC-HF underscore the potential of omecamtiv
mecarbil for the treatment of chronic heart failure, a disease that
remains a growing healthcare problem worldwide," said John Teerlink, M.D., professor of Clinical
Medicine at the University of California, San
Francisco and director of Heart Failure at the San Francisco
Veterans Affairs Medical Center. "The findings from COSMIC-HF
support the therapeutic hypothesis that directly improving cardiac
systolic function with a cardiac myosin activator may reverse
abnormal structural changes and neurohormonal activation associated
with the progression of heart failure."
The trial, which evaluated 448 patients with chronic heart
failure and left ventricular systolic dysfunction, showed that dose
titration controlled patient exposure to omecamtiv mecarbil.
Patients were randomized 1:1:1 to receive either placebo or
treatment with omecamtiv mecarbil dosed as 25 mg twice
daily or 25 mg with dose escalation to 50 mg twice daily, depending
on plasma concentrations of omecamtiv mecarbil after two
weeks of treatment.
The pharmacokinetic-based dose titration strategy was designed
to maintain patient exposure to omecamtiv mecarbil in the targeted
plasma concentration range. Approximately 53 percent of patients in
the dose titration group were escalated to a dose of 50 mg twice
daily.
Following 20 weeks of treatment, statistically significant
improvements were observed in all pre-specified secondary endpoint
measures of cardiac function in the dose titration group, compared
to placebo. Systolic ejection time increased by 25.0 msec
(p<0.0001), stroke volume increased by 3.6 mL
(p=0.0217) and heart rate decreased by 3.0 beats per min
(p=0.0070). Left ventricular end-systolic and end-diastolic
dimensions decreased by 1.8 mm (p=0.0027) and 1.3 mm
(p=0.0128), respectively, and were associated with
statistically significant reductions in left ventricular
end-systolic and end-diastolic volumes. N-terminal pro-brain
natriuretic peptide (NT-proBNP) decreased by 970 pg/mL
(p=0.0069). In pre-specified exploratory analyses of the
dose titration group, placebo-corrected reductions in NT-proBNP
persisted four weeks after stopping omecamtiv mecarbil, decreasing
further to 1,306 pg/mL (p=0.0006). The data also showed
increases in fractional shortening at week 20 compared to placebo
in the dose titration group.
"The mechanism of action for omecamtiv mecarbil is novel, and
these data reinforce its potential as a new therapy for the
millions of patients living with heart failure around the world,"
said Sean E. Harper, M.D., executive
vice president of Research and Development at Amgen. "In
collaboration with our partners Cytokinetics and Servier, we look
forward to initiating our Phase 3 clinical trial program for
omecamtiv mecarbil where we will learn if the improvements in
cardiac function observed in the COSMIC-HF study translate into
improved cardiovascular outcomes for patients."
"Results from COSMIC-HF provide further validation for the
pharmacodynamic effects of omecamtiv mecarbil and show its
potential to reverse ventricular enlargement in patients living
with chronic heart failure," said Robert I.
Blum, president and CEO at Cytokinetics. "We look forward to
advancing omecamtiv mecarbil into its Phase 3 program designed to
investigate correlations between cardiac function and clinical
outcomes."
Adverse events (AEs), including serious AEs, in patients on
omecamtiv mecarbil were comparable to placebo. The incidence of
adjudicated deaths (3 percent died on placebo, 1 percent died on
omecamtiv mecarbil 25 mg twice daily, 2 percent died on omecamtiv
mecarbil dose titration), myocardial infarction (1 percent on
placebo, 0 percent on omecamtiv mecarbil 25 mg twice daily, 1
percent on omecamtiv mecarbil dose titration) and unstable angina
(0 percent on placebo, 1 percent on omecamtiv mecarbil 25 mg twice
daily, 0 percent on omecamtiv mecarbil dose titration) was similar.
Other cardiac AEs were generally balanced between placebo and
active treatment groups. In patients receiving omecamtiv mecarbil
compared to placebo, cardiac troponin increased by 0.001 ng/mL and
0.006 ng/mL (median change from baseline at week 20) in the 25 mg
twice daily group and dose titration group, respectively. Events of
increased troponin (n=278 across all treatment groups) were
independently adjudicated and none were adjudicated as an episode
of myocardial ischemia or infarction.
About Heart Failure
Heart failure is a grievous
condition that affects more than 23 million people
worldwide,2,3 about half of whom have reduced left
ventricular function.4,5 It is the leading cause of
hospitalization and readmission in people age 65 and
older.6,7 Despite broad use of standard treatments and
advances in care, the prognosis for patients with heart failure is
poor.8 An estimated one in five people over the age of
40 are at risk of developing heart failure, and approximately 50
percent of people diagnosed with heart failure will die within five
years of initial hospitalization.9,10
COSMIC-HF Trial Design
COSMIC-HF (Chronic Oral Study
of Myosin Activation to Increase Contractility in Heart Failure)
was a double-blind, randomized, placebo-controlled, multicenter,
Phase 2 trial designed to evaluate an oral formulation of omecamtiv
mecarbil in chronic heart failure patients with reduced ejection
fraction. The trial consisted of two parts, a dose escalation phase
and a larger and longer expansion phase. The dose escalation phase,
which completed in 2013, assessed the pharmacokinetics and
tolerability of three oral modified-release formulations of
omecamtiv mecarbil and was used to select one formulation for
further evaluation in the expansion phase. In the dose escalation
phase, 96 patients were randomized 1:1:1:1 to placebo or one of
three oral modified-release formulations of omecamtiv mecarbil in
two cohorts (25 mg twice daily or 50 mg twice daily). Each patient
cohort was followed for 35 days.
The expansion phase evaluated 448 chronic heart failure patients
with reduced ejection fraction who were dosed with the selected
oral formulation of omecamtiv mecarbil for 20 weeks and followed
for a total of 24 weeks. Patients were randomized 1:1:1 to receive
either placebo or treatment with omecamtiv mecarbil 25 mg twice
daily or 25 mg with dose escalation to 50 mg twice daily, depending
on plasma concentrations of omecamtiv mecarbil after two weeks of
treatment. The pharmacokinetic-based dose titration strategy
was designed to maintain patient exposure to omecamtiv mecarbil in
a targeted plasma concentration range; approximately 53 percent of
patients in the dose titration group were escalated to a dose of 50
mg twice daily.
The primary endpoints for the expansion phase were to assess the
maximum and pre-dose plasma concentration of omecamtiv mecarbil.
The secondary endpoints were to assess changes from baseline in
systolic ejection time, stroke volume, left ventricular
end-systolic diameter, left ventricular end-diastolic diameter,
heart rate and NT-proBNP (a biomarker associated with the severity
of heart failure) at week 20, as well as the safety and
tolerability of omecamtiv mecarbil including incidence of adverse
events from baseline to week 24.
COSMIC-HF was not designed to assess the impact of omecamtiv
mecarbil on cardiovascular outcomes in heart failure patients.
COSMIC-HF was conducted by Amgen in collaboration with
Cytokinetics.
About Omecamtiv Mecarbil
Omecamtiv mecarbil is a novel cardiac myosin activator. Cardiac
myosin is the cytoskeletal motor protein in the cardiac muscle cell
that is directly responsible for converting chemical energy into
the mechanical force resulting in cardiac contraction. Cardiac
myosin activators are thought to accelerate the rate-limiting step
of the myosin enzymatic cycle and shift the enzymatic cycle in
favor of the force-producing state. Preclinical research has shown
that cardiac myosin activators increase contractility in the
absence of changes in intracellular calcium in cardiac
myocytes.11-13
Omecamtiv mecarbil is being developed by Amgen in collaboration
with Cytokinetics. Amgen holds an exclusive, worldwide license to
omecamtiv mecarbil and related compounds, subject to Cytokinetics'
specified development and commercialization rights. Servier has
exercised an exclusive option granted by Amgen for the
commercialization of omecamtiv mecarbil in Europe, as well as the Commonwealth of
Independent States, including Russia.
About Amgen Cardiovascular
Building on more than three
decades of experience in developing biotechnology medicines for
patients with serious illnesses, Amgen is dedicated to addressing
important scientific questions to advance care and improve the
lives of patients with cardiovascular disease, the leading cause of
morbidity and mortality worldwide.14 Amgen's research
into cardiovascular disease, and potential treatment options, is
part of a growing competency at Amgen that utilizes human genetics
to identify and validate certain drug targets. Through its own
research and development efforts, as well as partnerships, Amgen is
building a robust cardiovascular portfolio consisting of several
approved and investigational molecules in an effort to address a
number of today's important unmet patient needs, such as high
cholesterol and heart failure.
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.
For more information, visit www.amgen.com and follow us on
www.twitter.com/amgen.
About Cytokinetics
Cytokinetics is a late-stage
biopharmaceutical company focused on discovering, developing and
commercializing first-in-class muscle activators as potential
treatments for debilitating diseases in which muscle performance is
compromised and/or declining. As a leader in muscle biology and the
mechanics of muscle performance, the company is developing small
molecule drug candidates specifically engineered to increase muscle
function and contractility. Cytokinetics' lead drug candidate is
tirasemtiv, a fast skeletal muscle troponin activator, for
the potential treatment of ALS. Tirasemtiv has been granted
orphan drug designation and fast track status by the U.S. Food and
Drug Administration and orphan medicinal product designation by the
European Medicines Agency for the potential treatment of ALS.
Cytokinetics retains the right to develop and commercialize
tirasemtiv, subject to an option held by Astellas Pharma
Inc. Cytokinetics is also collaborating with Astellas to develop
CK-2127107, a fast skeletal muscle activator, for the potential
treatment of spinal muscular atrophy, chronic obstructive pulmonary
disease and ALS. Cytokinetics is collaborating with Amgen Inc. to
develop omecamtiv mecarbil, a novel cardiac muscle
activator, for the potential treatment of heart failure. Amgen
holds an exclusive license worldwide to develop and commercialize
omecamtiv mecarbil and Astellas holds an exclusive license
worldwide to develop and commercialize CK-2127107. Both licenses
are subject to Cytokinetics' specified development and
commercialization participation rights. For additional information
about Cytokinetics, visit http://www.cytokinetics.com.
Amgen Forward-Looking Statements
This news release
contains forward-looking statements that are based on the current
expectations and beliefs of Amgen. All statements, other than
statements of historical fact, are statements that could be deemed
forward-looking statements, including estimates of revenues,
operating margins, capital expenditures, cash, other financial
metrics, expected legal, arbitration, political, regulatory or
clinical results or practices, customer and prescriber patterns or
practices, reimbursement activities and outcomes and other such
estimates and results. Forward-looking statements involve
significant risks and uncertainties, including those discussed
below and more fully described in the Securities and Exchange
Commission reports filed by Amgen, including our most recent annual
report on Form 10-K and any subsequent periodic reports on Form
10-Q and Form 8-K. Unless otherwise noted, Amgen is providing this
information as of the date of this news release and does not
undertake any obligation to update any forward-looking statements
contained in this document as a result of new information, future
events or otherwise.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project.
Discovery or identification of new product candidates or
development of new indications for existing products cannot be
guaranteed and movement from concept to product is uncertain;
consequently, there can be no guarantee that any particular product
candidate or development of a new indication for an existing
product will be successful and become a commercial product.
Further, preclinical results do not guarantee safe and effective
performance of product candidates in humans. The complexity of the
human body cannot be perfectly, or sometimes, even adequately
modeled by computer or cell culture systems or animal models. The
length of time that it takes for us to complete clinical trials and
obtain regulatory approval for product marketing has in the past
varied and we expect similar variability in the future. Even when
clinical trials are successful, regulatory authorities may question
the sufficiency for approval of the trial endpoints we have
selected. We develop product candidates internally and through
licensing collaborations, partnerships and joint ventures. Product
candidates that are derived from relationships may be subject to
disputes between the parties or may prove to be not as effective or
as safe as we may have believed at the time of entering into such
relationship. Also, we or others could identify safety, side
effects or manufacturing problems with our products after they are
on the market.
Our results may be affected by our ability to successfully
market both new and existing products domestically and
internationally, clinical and regulatory developments involving
current and future products, sales growth of recently launched
products, competition from other products including biosimilars,
difficulties or delays in manufacturing our products and global
economic conditions. In addition, sales of our products are
affected by pricing pressure, political and public scrutiny and
reimbursement policies imposed by third-party payers, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
and domestic and international trends toward managed care and
healthcare cost containment. Furthermore, our research, testing,
pricing, marketing and other operations are subject to extensive
regulation by domestic and foreign government regulatory
authorities. We or others could identify safety, side effects or
manufacturing problems with our products after they are on the
market. Our business may be impacted by government investigations,
litigation and product liability claims. In addition, our business
may be impacted by the adoption of new tax legislation or exposure
to additional tax liabilities. If we fail to meet the compliance
obligations in the corporate integrity agreement between us and the
U.S. government, we could become subject to significant sanctions.
Further, while we routinely obtain patents for our products and
technology, the protection offered by our patents and patent
applications may be challenged, invalidated or circumvented by our
competitors, or we may fail to prevail in present and future
intellectual property litigation. We perform a substantial amount
of our commercial manufacturing activities at a few key facilities
and also depend on third parties for a portion of our manufacturing
activities, and limits on supply may constrain sales of certain of
our current products and product candidate development. In
addition, we compete with other companies with respect to many of
our marketed products as well as for the discovery and development
of new products. Further, some raw materials, medical devices and
component parts for our products are supplied by sole third-party
suppliers. The discovery of significant problems with a product
similar to one of our products that implicate an entire class of
products could have a material adverse effect on sales of the
affected products and on our business and results of operations.
Our efforts to acquire other companies or products and to integrate
the operations of companies we have acquired may not be successful.
We may not be able to access the capital and credit markets on
terms that are favorable to us, or at all. We are increasingly
dependent on information technology systems, infrastructure and
data security. Our stock price is volatile and may be affected by a
number of events. Our business performance could affect or limit
the ability of our Board of Directors to declare a dividend or our
ability to pay a dividend or repurchase our common stock.
The scientific information discussed in this news release
related to our product candidates is preliminary and investigative.
Such product candidates are not approved by the U.S. Food and
Drug Administration or European Commission, and no
conclusions can or should be drawn regarding the safety or
effectiveness of the product candidates.
Cytokinetics Forward-Looking Statements
This press
release contains forward-looking statements for purposes of the
Private Securities Litigation Reform Act of 1995 (the "Act").
Cytokinetics disclaims any intent or obligation to update these
forward-looking statements, and claims the protection of the Act's
Safe Harbor for forward-looking statements. Examples of such
statements include, but are not limited to, statements relating to
Cytokinetics' and its partners' research and development
activities, including the significance and utility of
COSMIC-HF clinical trial results and the potential
progression of omecamtiv mecarbil to Phase 3 development;
and the properties and potential benefits of Cytokinetics' drug
candidates. Such statements are based on management's current
expectations, but actual results may differ materially due to
various risks and uncertainties, including, but not limited to
Amgen's decisions with respect to the design, initiation, conduct,
timing and continuation of development activities for omecamtiv
mecarbil; potential difficulties or delays in the development,
testing, regulatory approvals for trial commencement, progression
or product sale or manufacturing, or production of Cytokinetics'
drug candidates that could slow or prevent clinical development or
product approval, including risks that current and past results of
clinical trials or preclinical studies may not be indicative of
future clinical trials results, patient enrollment for or conduct
of clinical trials may be difficult or delayed, Cytokinetics' drug
candidates may have adverse side effects or inadequate therapeutic
efficacy, the U.S. Food and Drug Administration or foreign
regulatory agencies may delay or limit Cytokinetics' or its
partners' ability to conduct clinical trials, and Cytokinetics may
be unable to obtain or maintain patent or trade secret protection
for its intellectual property; Cytokinetics may incur unanticipated
research and development and other costs or be unable to obtain
additional financing necessary to conduct development of its
products; standards of care may change, rendering Cytokinetics'
drug candidates obsolete; competitive products or alternative
therapies may be developed by others for the treatment of
indications Cytokinetics' drug candidates and potential drug
candidates may target; and risks and uncertainties relating to the
timing and receipt of payments from its partners, including
milestones and royalties on future potential product sales under
Cytokinetics' collaboration agreements with such partners. For
further information regarding these and other risks related to
Cytokinetics' business, investors should consult Cytokinetics'
filings with the Securities and Exchange Commission.
Forward-looking statements are not guarantees of future
performance, and Cytokinetics' actual results of operations,
financial condition and liquidity, and the development of the
industry in which it operates, may differ materially from the
forward-looking statements contained in this press release. Any
forward-looking statements that Cytokinetics makes in this press
release speak only as of the date of this press release.
Cytokinetics assumes no obligation to update its forward-looking
statements whether as a result of new information, future events or
otherwise, after the date of this press release.
CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(media)
Kristen Neese, 805-313-8267
(media)
Arvind Sood, 805-447-1060
(investors)
CONTACT: Cytokinetics, South San
Francisco
Diane Weiser, 415-290-7757
(investors and media)
References
- Teerlink J, Felker GM, et al. Chronic Oral Study of Myosin
Activation to Increase Contractility in Heart Failure (COSMIC-HF):
Results from a Double-blind, Randomized, Placebo-controlled,
Multicenter Study. Circulation. 2015;132(23).
- Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile
of heart failure. Nat Rev Cardiol. 2011;8(1):30-41.
- McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical epidemiology of heart
failure: public and private health burden. Eur Heart
J. 1998;19 (Suppl P):P9–P16.
- Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline
for the Management of Heart failure: A Report of the American
College of Cardiology Foundation/American Heart Association Task
Force on Practice Guidelines. Circulation.
2013;128:e240-e327.
- Ponikowski P, Voors AA, Anker SD, et al. 2016
ESC guidelines for the diagnosis and treatment of acute and chronic
heart failure: The Task Force for the diagnosis and treatment of
acute and chronic heart failure of the European Society of
Cardiology (ESC). Developed with the special contribution of
the Heart Failure Association (HFA) of the ESC. Eur
Heart J. 2016;37:2129–2200.
- Centers for Disease Control and Prevention. National Health
Statistics Report: 2006 National Hospital Discharge Survey.
http://www.cdc.gov/nchs/data/nhsr/nhsr005.pdf. Accessed
September 2016.
- Jencks SF, Williams MV, Coleman EA. Rehospitalizations among
Patients in the Medicare Fee-for-Service Program. NEJM.
2009;360:1418-1428.
- Jhund PS, MacIntyre K, Simpson CR, et al. Long-Term Trends in
First Hospitalization for Heart Failure and Subsequent Survival
Between 1986 and 2003. Circulation. 2009;119:515-523.
- Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and
Stroke Statistics—2015 Update: A Report From the American Heart
Association. Circulation. 2015;131:e1-e294.
- Rogers VL, Weston SA, Redfield MM, et al. Trends in Heart
Failure Incidence and Survival in a Community-Based Population.
JAMA. 2004;292:344-350.
- Malik FI, Hartman JJ, Elias KA, et al. Cardiac myosin
activation: a potential therapeutic approach for systolic heart
failure. Science. 2011;331(6023):1439-1443.
- Shen YT, Malik FI, Zhao X, et al. Improvement of Cardiac
Function by a Cardiac Myosin Activator in Conscious Dogs With
Systolic Heart Failure. Circ Heart Fail.
2010;3(4):522-527.
- Malik FI, Morgan BP. Cardiac myosin activation part 1: From
concept to clinic. J Mol Cell Cardiol. 2011;51:454-461.
- World Health Organization. Cardiovascular diseases (CVDs) fact
sheet. http://www.who.int/mediacentre/factsheets/fs317/en/.
Accessed September 2016.
Logo - http://photos.prnewswire.com/prnh/20081015/AMGENLOGO
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/the-lancet-publishes-results-from-cosmic-hf-trial-showing-omecamtiv-mecarbil-significantly-improved-cardiac-function-in-patients-with-chronic-heart-failure-300370905.html
SOURCE Amgen