THOUSAND OAKS, Calif.
and SOUTH SAN FRANCISCO,
Calif. and SURESNES, France, Oct. 8, 2020 /PRNewswire/ -- Amgen
(NASDAQ:AMGN), Cytokinetics, Incorporated (NASDAQ:CYTK) and Servier
today announced topline results from GALACTIC-HF, a Phase 3 pivotal
clinical trial of omecamtiv mecarbil in patients with heart failure
with reduced ejection fraction (HFrEF).
The results of GALACTIC-HF show that treatment with omecamtiv
mecarbil achieved the primary composite efficacy endpoint and
demonstrated a statistically significant effect to
reduce cardiovascular (CV) death or heart failure events
(heart failure hospitalization and other urgent treatment for heart
failure) compared to placebo in patients treated with standard of
care (HR: 0.92; 95% CI: 0.86, 0.99, p=0.0252).
No reduction in the secondary endpoint of CV death was observed.
Adverse events, including major ischemic cardiac events, were
balanced between treatment arms. Additional analyses of data are
underway and results from GALACTIC-HF will be presented at the
American Heart Association (AHA) Scientific Sessions 2020, in a
virtual Late Breaking Clinical Trial session on Friday, November 13, 2020 from 10:35-10.45 a.m. CDT.
Omecamtiv mecarbil is an investigational cardiac myosin
activator, the first of a novel class of myotropes1
designed to directly target the contractile mechanisms of the
heart.
"The outcomes observed in GALACTIC-HF further the understanding
of treating heart failure, a devastating disease in which half of
heart failure patients will die within five years of initial
hospitalization," said David M. Reese, M.D. executive vice
president of Research and Development at Amgen. "At Amgen, we
remain committed to developing and delivering transformative
medicines that improve the lives of patients with cardiovascular
disease."
"GALACTIC-HF provides insights into effects associated with
targeting cardiac muscle contractility with omecamtiv mecarbil to
treat heart failure patients with reduced ejection fraction," said
Fady I. Malik, M.D., Ph.D., Cytokinetics' executive vice president
of Research & Development. "We are grateful to the trial
investigators, site personnel, patients and caregivers who
participated in the trial, and we look forward to further data
analyses and the presentation of the results of this Phase 3 trial
at the American Heart Association Scientific Sessions."
"Heart failure is a devastating condition jeopardizing patients'
lives every day. We are pleased to have collaborated with Amgen and
Cytokinetics on one of the largest heart failure trials ever
conducted to investigate this novel therapy in patients with heart
failure. It is important to now turn our attention to fully
analyzing the data from this important study in this clinical
setting," said Claude Bertrand,
PharmD, PhD, Executive Vice President R&D at Servier.
GALACTIC-HF: Trial Design
GALACTIC-HF,2
(Global Approach to Lowering Adverse
Cardiac Outcomes Through Improving
Contractility in Heart Failure), one of the
largest Phase 3 global cardiovascular outcomes studies in heart
failure ever conducted, enrolled 8,256 patients in 35 countries
with HFrEF, New York Heart Association (NYHA) class II-IV, left
ventricular ejection fraction (LVEF) ≤35%, elevated natriuretic
peptides and either current hospitalization for heart failure or
history of hospitalization or emergency department visit for heart
failure within a year. Patients were randomized to either oral
placebo or a starting dose of 25 mg omecamtiv mecarbil twice daily
(maintenance dose of 50 mg, 37.5 mg, or 25 mg twice daily) guided
by pharmacokinetic-guided dose selection. A blood test, the QMS
Omecamtiv Mecarbil Immunoassay (the OM Test) was used to measure
plasma levels of omecamtiv mecarbil in each patient in order to
guide selection of the appropriate maintenance dose.
The primary composite endpoint of this double-blind,
placebo-controlled, event-driven trial was time to CV death or
first heart failure event (heart failure hospitalization and other
urgent treatment for heart failure). Secondary endpoints were: time
to CV death, patient reported outcomes (measured by Kansas City
Cardiomyopathy Questionnaire [KCCQ] Total Symptom Score [TSS]),
time to first heart failure hospitalization and time to all-cause
death.
About Omecamtiv Mecarbil and the Phase 3 Clinical Trials
Program
Omecamtiv mecarbil is an investigational selective
cardiac myosin activator, the first of a novel class of
myotropes1 designed to directly target the contractile
mechanisms of the heart, binding to and recruiting more cardiac
myosin heads to interact with actin during systole. Preclinical
research has shown that omecamtiv mecarbil increases cardiac
contractility without increasing intracellular myocyte calcium
concentrations or myocardial oxygen consumption.3-5
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.
Omecamtiv mecarbil is being developed for the potential
treatment of heart failure with reduced ejection fraction (HFrEF)
under a collaboration between Amgen and Cytokinetics, with funding
and strategic support from Servier. Omecamtiv mecarbil is the
subject of a comprehensive Phase 3 clinical trials program composed
of GALACTIC-HF and METEORIC-HF (Multicenter Exercise
Tolerance Evaluation of Omecamtiv
Mecarbil Related to Increased
Contractility in Heart Failure), a Phase 3
clinical trial designed to evaluate the effect of treatment with
omecamtiv mecarbil compared to placebo on exercise
capacity.
About Heart Failure
Heart failure is a grievous
condition that affects more than 64 million people
worldwide6 about half of whom have reduced left
ventricular function.7,8 It is the leading cause of
hospitalization and readmission in people age 65 and
older.9,10 Despite broad use of standard treatments and
advances in care, the prognosis for patients with heart failure is
poor.11 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.12,13
About Cytokinetics and Amgen Collaboration
In 2006,
Cytokinetics and Amgen entered into a strategic alliance to
discover, develop and commercialize novel small molecule
therapeutics designed to activate the cardiac sarcomere for the
potential treatment of heart failure. Omecamtiv mecarbil is
being developed by Amgen in collaboration with Cytokinetics, with
funding and strategic support from Servier. Amgen holds an
exclusive, worldwide license to omecamtiv mecarbil and related
compounds, subject to Cytokinetics' specified development and
commercialization rights. Cytokinetics is eligible for
pre-commercialization and commercialization milestone payments and
royalties that escalate based on increasing levels of annual net
sales of products commercialized under the agreement. Cytokinetics
has co-invested with Amgen in the Phase 3 development program of
omecamtiv mecarbil in exchange for increased royalties from Amgen
on worldwide sales of omecamtiv mecarbil outside Japan and co-promotion rights in institutional
care settings in North America. Amgen has also entered an
alliance with Servier for exclusive commercialization rights for
omecamtiv mecarbil in Europe as
well as the Commonwealth of Independent States, including
Russia. Servier
contributes funding for development and provides strategic
support to the program.
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 biologics manufacturing 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 the world's
largest independent biotechnology company, 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 and next-in-class
muscle inhibitors 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 impact muscle function and
contractility. Cytokinetics is collaborating with Amgen Inc.
(Amgen) to develop omecamtiv mecarbil, a novel cardiac muscle
activator. Omecamtiv mecarbil is the subject of an international
clinical trials program in patients with heart failure including
GALACTIC-HF and METEORIC-HF. Amgen holds an exclusive worldwide
license to develop and commercialize omecamtiv mecarbil with a
sublicense held by Servier for commercialization in Europe and certain other countries.
Cytokinetics is developing reldesemtiv, a fast skeletal
muscle troponin activator (FSTA) for the potential treatment of ALS
and other neuromuscular indications following conduct of
FORTITUDE-ALS and other Phase 2 clinical trials. The company is
considering potential advancement of reldesemtiv to Phase 3
pending ongoing regulatory interactions. Cytokinetics is
collaborating with Astellas Pharma Inc. (Astellas) to research,
develop and commercialize other novel mechanism skeletal sarcomere
activators (not including FSTAs). Licenses held by Amgen and
Astellas are subject to specified co-development and
co-commercialization rights of Cytokinetics. Cytokinetics is also
developing CK-274, a novel cardiac myosin inhibitor that company
scientists discovered independent of its collaborations, for the
potential treatment of hypertrophic cardiomyopathies. Cytokinetics
has granted Ji Xing Pharmaceuticals Limited an exclusive license to
develop and commercialize CK-274 in China and Taiwan, in accordance with Cytokinetics'
planned global registration programs. Cytokinetics is conducting
REDWOOD-HCM, a Phase 2 clinical trial of CK-274 in patients with
obstructive HCM. Cytokinetics continues its over 20-year history of
pioneering innovation in muscle biology and related pharmacology
focused to diseases of muscle dysfunction and conditions of muscle
weakness.
For additional information about Cytokinetics, visit
www.cytokinetics.com and follow us on Twitter, LinkedIn, Facebook
and YouTube.
About Servier
Servier is an international
pharmaceutical company governed by a non-profit foundation, with
its headquarters in France
(Suresnes). With a strong international presence in 150 countries
and a turnover of 4.6 billion euros
in 2019, Servier employs 22,000 people worldwide. Entirely
independent, the Group reinvests in average 25% of its turnover
(excluding generics) every year in research and development and
uses all its profits for development. Corporate growth is driven by
Servier's constant commitment in five areas of excellence:
cardiovascular, immune-inflammatory and neurodegenerative diseases,
cancer and diabetes, as well as by its activities in high-quality
generic drugs. Servier also offers eHealth solutions beyond drug
development.
More information: www.servier.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 any statements on the
outcome, benefits and synergies of collaborations, or potential
collaborations, with any other company, including BeiGene, Ltd. or
any collaboration or potential collaboration in pursuit of
therapeutic antibodies against COVID-19 (including statements
regarding such collaboration's, or our own, ability to discover and
develop fully-human neutralizing antibodies targeting SARS-CoV-2 or
antibodies against targets other than the SARS-CoV-2 receptor
binding domain, and/or to produce any such antibodies to
potentially prevent or treat COVID-19), or the Otezla®
(apremilast) acquisition, including anticipated Otezla sales growth
and the timing of non-GAAP EPS accretion, as well as 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, effects of pandemics or other widespread health problems
such as the ongoing COVID-19 pandemic on our business, outcomes,
progress, or effects relating to studies of Otezla as a potential
treatment for COVID-19, 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 its most recent annual report on Form 10-K and
any subsequent periodic reports on Form 10-Q and current reports on
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 Amgen projects. 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
Amgen to complete clinical trials and obtain regulatory approval
for product marketing has in the past varied and Amgen expects
similar variability in the future. Even when clinical trials are
successful, regulatory authorities may question the sufficiency for
approval of the trial endpoints Amgen has selected. Amgen develops
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 Amgen may
have believed at the time of entering into such relationship. Also,
Amgen or others could identify safety, side effects or
manufacturing problems with its products, including its devices,
after they are on the market.
Amgen's results may be affected by its 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 its products and global
economic conditions. In addition, sales of Amgen's 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, Amgen's research,
testing, pricing, marketing and other operations are subject to
extensive regulation by domestic and foreign government regulatory
authorities. Amgen's business may be impacted by government
investigations, litigation and product liability claims. In
addition, Amgen's business may be impacted by the adoption of new
tax legislation or exposure to additional tax liabilities. If Amgen
fails to meet the compliance obligations in the corporate integrity
agreement between Amgen and the U.S. government, Amgen could become
subject to significant sanctions. Further, while Amgen routinely
obtains patents for its products and technology, the protection
offered by its patents and patent applications may be challenged,
invalidated or circumvented by its competitors, or Amgen may fail
to prevail in present and future intellectual property litigation.
Amgen performs a substantial amount of its commercial manufacturing
activities at a few key facilities, including in Puerto Rico, and also depends on third parties
for a portion of its manufacturing activities, and limits on supply
may constrain sales of certain of its current products and product
candidate development. An outbreak of disease or similar public
health threat, such as COVID-19, and the public and governmental
effort to mitigate against the spread of such disease, could have a
significant adverse effect on the supply of materials for Amgen's
manufacturing activities, the distribution of Amgen's products, the
commercialization of Amgen's product candidates, and Amgen's
clinical trial operations, and any such events may have a material
adverse effect on Amgen's product development, product sales,
business and results of operations. Amgen relies on collaborations
with third parties for the development of some of its product
candidates and for the commercialization and sales of some of its
commercial products. In addition, Amgen competes with other
companies with respect to many of its marketed products as well as
for the discovery and development of new products. Further, some
raw materials, medical devices and component parts for Amgen's
products are supplied by sole third-party suppliers. Certain of
Amgen's distributors, customers and payers have substantial
purchasing leverage in their dealings with Amgen. The discovery of
significant problems with a product similar to one of Amgen's
products that implicate an entire class of products could have a
material adverse effect on sales of the affected products and on
its business and results of operations. Amgen's efforts to
collaborate with or acquire other companies, products or
technology, and to integrate the operations of companies or to
support the products or technology Amgen has acquired, may not be
successful. A breakdown, cyberattack or information security breach
could compromise the confidentiality, integrity and availability of
Amgen's systems and Amgen's data. Amgen's stock price may be
volatile and may be affected by a number of events. Amgen's
business performance could affect or limit the ability of the Amgen
Board of Directors to declare a dividend or its ability to pay a
dividend or repurchase its common stock. Amgen may not be able to
access the capital and credit markets on terms that are favorable
to it, or at all.
The scientific information discussed in this news release
related to Amgen's product candidates is preliminary and
investigative. Such product candidates are not approved by the U.S.
Food and Drug Administration, 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
GALACTIC-HF; the potential benefits of omecamtiv mecarbil,
including its ability to represent a novel therapeutic strategy to
increase cardiac muscle function and restore cardiac performance;
the approval of omecamtiv mecarbil by the FDA or any other
regulatory agency; the successful marketing and commercialization
of omecamtiv mecarbil; Cytokinetics' and its partners' research and
development activities; the design, timing, results, significance
and utility of preclinical and clinical results; and the properties
and potential benefits of Cytokinetics' drug candidates. Such
statements are based on management's current expectations and
beliefs, but actual results may differ materially due to various
risks and uncertainties, including, but not limited to, 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; the
impact of the COVID-19 pandemic on our research and development
activities and business operations, Cytokinetics' drug candidates
may have adverse side effects or inadequate therapeutic efficacy;
the FDA or foreign regulatory agencies may delay or limit
Cytokinetics' or its partners' ability to conduct clinical trials;
Cytokinetics may be unable to obtain or maintain patent or trade
secret protection for its intellectual property; Amgen's decisions
with respect to the design, initiation, conduct, timing and
continuation of development activities for omecamtiv mecarbil;
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.
CONTACT: Amgen, Thousand
Oaks
Trish Rowland, 805-447-5631
(media)
Jessica Akopyan, 805-447-0974 (media)
Arvind Sood, 805-447-1060
(investors)
CONTACT: Cytokinetics
Diane Weiser, Senior Vice President,
Corporate Communications, Investor Relations
415-290-7757
CONTACT: Servier
Sonia Marques:
sonia.marques@servier.com
– Tel. +33 (0)1 55 72 40 21 / + 33 (0) 7 84 28 76 13
Jean-Clément Vergeau: jean-clement.vergeau@servier.com
– Tel. +33 (0)1 55 72 46 16 / + 33 (0) 6 79 56 75 96
References
- Psotka MA, Gottlieb SS, Francis GS et al. Cardiac Calcitropes,
Myotropes, and Mitotropes. JACC. 2019; 73:2345-53.
- Teerlink JR., Diaz R., Felker GM., et al. Omecamtiv Mecarbil in
Chronic Heart Failure With Reduced Ejection Fraction:
Rationale and Design of GALACTIC-HF. JACC Heart Fail.
2020 Apr; 8(4):329-340.
doi: 10.1016/j.jchf.2019.12.001.Epub 2020 Feb 6.
- Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J. et al.
Mechanistic and structural basis for activation of cardiac myosin
force production by omecamtiv mecarbil. Nat Commun. 2017;8:190.
- 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:
522-27.
- Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc
K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R. Cardiac
myosin activation: a potential therapeutic approach for systolic
heart failure. Science. 2011 Mar
18;331(6023):1439-43.
- GBD 2017 Disease and Injury Incidence and Prevalence
Collaborators. Lancet 2018; 392: 1789–858.
- 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.
- Roger VL. Epidemiology of Heart Failure. Circulation
Research. 2013;113:646-659, originally published August
29, 2013. Doi: 10.1161/CIRCRESAHA.113.300268.
- Kilgore M, Patel HK, Kielhorn A et al. Economic burden of
hospitalizations of Medicare beneficiaries with heart
failure. Risk Manag Healthc Policy. 2017; 10:
63-70.
- 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.
- Benjamin EJ, Virani SS, Callaway CW et al. Heart Disease and
Stroke Statistics—2018 Update: A Report From the American
Heart Association. Circulation.
2018;137:e67-e492.
- Roger VL, Weston SA, Redfield MM, et al. Trends in Heart
Failure Incidence and Survival in a Community-Based
Population. JAMA. 2004;292:344-350.
View original content to download
multimedia:http://www.prnewswire.com/news-releases/amgen-cytokinetics-and-servier-announce-topline-results-from-galactic-hf-a-phase-3-trial-of-omecamtiv-mecarbil-in-patients-with-heart-failure-301148269.html
SOURCE Amgen