Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that
additional 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, 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, at the 17th Global Cardiovascular Clinical Trialists
Forum (CVCT).
“These results shed light on advanced heart
failure patients who may benefit more from potential treatment with
omecamtiv mecarbil,” said John Teerlink, M.D. “These sicker
patients continue to have substantial persistent risk despite
receiving standard of care therapy and, based on the progressive
nature of their disease, are frequently unable to tolerate
guideline-directed medical therapy as their disease worsens. These
additional data from GALACTIC-HF suggest that omecamtiv mecarbil
may provide a new treatment option for this critical population of
patients.”
GALACTIC-HF: Supplemental
Analyses
GALACTIC-HF enrolled 8,256 patients who were at
risk of hospitalization and death, despite being well treated on
standard of care therapy. As previously reported, 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 heart
failure events (heart failure hospitalization and other urgent
treatment for heart failure) or cardiovascular (CV) death compared
to placebo in patients treated with standard of care (hazard ratio,
0.92; 95% confidence interval [CI] 0.86, 0.99; p=0.025). No
reduction in the secondary endpoint of time to CV death was
observed in the overall population1.
The effect of omecamtiv mecarbil on the primary
composite endpoint in GALACTIC-HF 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=4,456, hazard ratio, 0.84; 95% CI 0.77,
0.92; interaction p=0.003). Supplemental analyses of this lower
ejection fraction subgroup in GALACTIC-HF presented at CVCT showed
that this potentially greater treatment effect in patients who
received omecamtiv mecarbil was consistently observed in patients
with characteristics that may indicate advanced heart failure
status, such as being hospitalized within the last 3 months (HR
0.83, 95% CI 0.74 – 0.93, p=0.001), having New York Association
Class III or IV heart failure (HR 0.80, 95% CI 0.71 – 0.90,
p<0.001), higher N-terminal-pro brain natriuretic peptide levels
(HR 0.77, 95% CI 0.69 – 0.87, p<0.001), and lower blood
pressures (HR 0.81, 95% CI 0.70 – 0.92, p=0.002). The absolute risk
reductions (ARR) ranged from 5.2% to 8.1% in these subgroups as
compared to the ARR of 2.1% observed in the overall population.
Additionally, a supplemental analysis of the
continuous relationship between ejection fraction and the hazard
ratio for the primary composite endpoint in GALACTIC-HF suggested a
potentially stronger treatment effect of omecamtiv mecarbil in
patients with increasingly lower ejection fractions.
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/a6f54df3-faaf-4c79-9ab4-9297bf42fbff
“These new data from GALACTIC-HF reinforce the
relationship between the primary pharmacologic effect of omecamtiv
mecarbil to improve cardiac systolic function and its impact on
heart failure outcomes, as it stands to reason that those with more
impaired function may benefit most from this novel mechanism
therapy,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive
Vice President of Research & Development. “We look forward to
sharing additional analyses in upcoming publications and
presentations which will elaborate further on these and other
ongoing analyses of data arising from GALACTIC-HF.”
GALACTIC-HF: Trial Design
And Primary Results
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. 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). No
reduction in the secondary endpoint of time to CV death was
observed in the overall population. The effect on the primary
endpoint was observed without evidence of an increase in the
overall rates of myocardial ischemic events, ventricular
arrhythmias or death from cardiovascular or all causes.
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) and 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
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 preparing for regulatory
interactions for omecamtiv mecarbil, its novel cardiac muscle
activator, following positive results from GALACTIC-HF, a large,
international Phase 3 clinical trial in patients with heart
failure. Cytokinetics is conducting METEORIC-HF, a second Phase 3
clinical trial of omecamtiv mecarbil. Cytokinetics is also
developing CK-274, a next- generation cardiac myosin inhibitor, for
the potential treatment of hypertrophic cardiomyopathies (HCM).
Cytokinetics is conducting REDWOOD-HCM, a Phase 2 clinical trial of
CK-274 in patients with obstructive HCM. Cytokinetics is also
developing reldesemtiv, a fast skeletal muscle troponin activator
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 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 and the timing of such approvals;
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;
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:CytokineticsDiane WeiserSenior Vice
President, Corporate Communications, Investor Relations(415)
290-7757
References
- Teerlink J et al. NEJM. 2020
- 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.
- Psotka MA, Gottlieb SS, Francis GS et
al. Cardiac Calcitropes, Myotropes, and Mitotropes. JACC.
2019; 73:2345-53.
- 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.
- James et al. 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.
Cytokinetics (NASDAQ:CYTK)
Historical Stock Chart
From Aug 2024 to Sep 2024
Cytokinetics (NASDAQ:CYTK)
Historical Stock Chart
From Sep 2023 to Sep 2024