Item 8.01. Other Events.
On November 13, 2020 Cytokinetics, Incorporated
(“Cytokinetics”) announced the primary results from GALACTIC-HF (Global Approach to Lowering Adverse
Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 event-driven
cardiovascular outcomes clinical trial of omecamtiv mecarbil. The results were presented by John Teerlink, M.D., Professor
of Medicine, University of California San Francisco, Director of Heart Failure, San Francisco Veterans Affairs Medical Center and
Executive Committee Chair, GALACTIC-HF, in a Late Breaking Clinical Trial session at the American Heart Association (AHA) Scientific
Sessions 2020, and were simultaneously published in the New England Journal of Medicine.1
GALACTIC-HF, one of the largest Phase 3
global cardiovascular outcomes trials in heart failure ever conducted, enrolled 8,256 patients who were at risk of hospitalization
and death, despite being well treated on standard of care therapy. After a median duration of follow-up of 21.8 months, the trial
demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite
endpoint of 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. A first primary endpoint event occurred in 1,523 of 4,120
patients (37.0%) in the omecamtiv mecarbil group and in 1,607 of 4,112 patients (39.1%) in the placebo group (hazard ratio,
0.92; 95% confidence interval [CI] 0.86, 0.99; p=0.025). This effect was observed without evidence of an increase in the overall
rates of myocardial ischemic events, ventricular arrhythmias or death from cardiovascular or all causes.
The statistically significant reduction
in the composite of heart failure events or cardiovascular deaths, without significant imbalances in the overall incidence of adverse
events across treatment arms, was observed in one of the broadest and most diverse range of patients enrolled in a contemporary
heart failure trial. GALACTIC-HF included both inpatients and outpatients, and with a high representation of participants with
moderate to severe heart failure symptoms as well as lower ejection fraction, systolic blood pressure and renal function.
No reduction in the secondary endpoint
of time to CV death was observed. Death from cardiovascular causes occurred in 808 (19.6%) patients treated with omecamtiv mecarbil
and 798 patients (19.4%) assigned to placebo (hazard ratio, 1.01; 95% CI, 0.92 to 1.11; p=0.86). The pre-specified analysis of
change from baseline to week 24 in the KCCQ total symptom score by randomization setting (inpatient mean difference [95% CI]: 2.50
[0.54, 4.46], outpatient mean difference: -0.46 [-1.40, 0.48], joint P = 0.028) did not meet the significance threshold of P=0.002
based upon the multiplicity control testing procedure. No other secondary endpoints were met in accordance with the prespecified
statistical analysis.
The effect of omecamtiv mecarbil
was consistent across most prespecified subgroups and with a potentially greater treatment effect suggested in patients with a
lower left ventricular ejection fraction (LVEF ≤28%, n=>4,000, hazard ratio, 0.84; 95% CI 0.77, 0.92; interaction p=0.003).
Omecamtiv mecarbil also significantly decreased NT-proBNP concentrations by 10 % (95% CI 6-14%) at Week 24 compared to placebo.
The overall safety profile of omecamtiv
mecarbil in GALACTIC-HF appears to be consistent with data from previous trials. Adverse events and treatment discontinuation
of study drug were balanced between the treatment arms. In general, the overall rates of myocardial ischemia, ventricular arrhythmias
and death were similar between treatment and placebo groups. Additionally, there was no significant difference in the change in
systolic blood pressure between baseline and at 24 or 48 weeks between the omecamtiv mecarbil and placebo groups. There
was a small but significant decrease in heart rate in participants assigned to omecamtiv mecarbil compared to placebo at
both timepoints. Median cardiac troponin I concentration increased 4 ng/L (95% CI 3-5; limit of detection, 6 ng/L) from baseline
with omecamtiv mecarbil compared to placebo.
Investor/Media Event
Cytokinetics will host an investor and
media event on November 13, 2020 at 1:00 PM ET that will be simultaneously webcast and can be accessed at https://wsw.com/webcast/cc/cytk/1388034
as well as from the Investors & Media section of Cytokinetics’ website at www.cytokinetics.com. An archived replay
of the virtual event will be available via Cytokinetics’ website until November 13, 2021.
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 across 945 sites 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 myotropes3 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.4-6 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 worldwide7 about half of whom have reduced left ventricular function.8,9
It is the leading cause of hospitalization and readmission in people age 65 and older.10, 11 Despite broad use
of standard treatments and advances in care, the prognosis for patients with heart failure is poor.12 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.13,14
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 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, of which topline results were recently reported, and METEORIC-HF, which is ongoing. 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.
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 the GALACTIC-HF clinical trial;
statements relating to the METEORIC-HF clinical trial; 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
potential approval of omecamtiv mecarbil by the FDA or any other regulatory authority; 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' other 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, 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; 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;
the nature of 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:
Cytokinetics
Diane
Weiser
Senior
Vice President, Corporate Communications, Investor Relations
(415)
290-7757
References
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1.
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Teerlink J et al. NEJM. 2020
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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.
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