HEART FAILURE

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HEART
FAILURE
ABOUT
Heart failure is a chronic, progressive condition that develops when the pumping
action of the heart is inadequate to meet the body’s needs for blood and oxygen.
The leading causes of heart failure are diseases that damage the heart muscle function,
including coronary heart disease and high blood pressure.
The normal, healthy heart is a muscular organ that pumps blood
continuously throughout the body. The right side of the heart
pumps oxygen-depleted blood from the veins into the lungs.
The left side of the heart pumps oxygen-rich blood from the
lungs out through the arteries to the rest of the body. When the
heart muscle contracts (called systole) blood is pumped out of
the heart, and when the heart muscle relaxes (called diastole)
blood enters the heart.
• People who are overweight. Being overweight increases
your risk of heart disease and type 2 diabetes, which can lead
to heart failure.
• People who have had a heart attack. Heart attacks can
cause damage that weakens the heart.
• Males. Men have been shown to have a higher rate of heart
failure than women.
Heart failure can affect the right side of the heart only, or both
sides of the heart. Right-side heart failure occurs when the heart
can’t pump enough blood to the lungs, resulting in fluid buildup
in the feet, ankles, legs, liver, abdomen, and the veins in the
neck. Left-side heart failure occurs when the heart can’t pump
enough oxygen-rich blood to the rest of the body, and as a
consequence, blood may back up into the lungs. Both left and
right-sided heart failure may occur together and can lead to
shortness of breath and fatigue.1
The most common signs and symptoms of heart failure are
shortness of breath, leg swelling, fatigue, persistent cough or
wheezing, confusion or impaired thinking, increased heart rate
and lack of appetite or nausea.5
PREVALENCE OF HEART FAILURE
Almost 6 million people in the United States have heart failure1,
resulting in nearly one million hospitalizations2 and almost
300,000 deaths each year1. For people over 65, the incidence of
heart failure approaches 10 per 1000.3 The annual cost of heart
failure to the U.S. health care system is estimated to be $32
billion, which includes the cost of health care services, medications to treat heart failure and missed days of work.4
Heart failure is more common in:1
• People who are 65 years old or older. Heart failure is the
most common reason for hospital admittance among
Medicare patients.
• African Americans. African Americans are more likely than
people of other races to have heart failure and are more likely
to have symptoms at a younger age, have more hospital visits
due to heart failure, and eventually die from heart failure.
SYMPTOMS OF HEART FAILURE
All of these symptoms are the result of a build-up of fluid in the
body or the poor delivery of blood to the tissues. As the heart
muscle grows weaker, symptoms may get worse. In severe
cases, patients may have shortness of breath even while lying
flat. The build-up of fluid associated with worsening heart failure
can also cause weight gain, frequent urination, and a cough that
is aggravated at night and when lying down1.
DIAGNOSING HEART FAILURE
Heart failure is diagnosed based on medical and family histories,
a physical examination and test results. No single test can
diagnose heart failure, so a physician may recommend one or
more of the following tests and refer the patient to a cardiologist:
exercise stress test, blood tests, chest X-ray, electrocardiogram
(EKG) coronary angiography, echocardiography or radionuclide
ventriculography or multiple-gated acquisition scanning (MUGA).5
In order to determine the best course of therapy, physicians
often assess the stage of heart failure according to the New York
Heart Association (NYHA) Functional Classifications. This system
relates symptoms to everyday activities and the patient's quality
of life.5
TREATING HEART FAILURE
NYHA FUNCTIONAL CLASSIFICATION
The goals for heart failure treatment include treating the underlying
cause, reducing symptoms, preventing the heart failure from worsening and improving quality of life.1
CLASS
SYMPTOMS
Class I (Mild)
No limitation of physical activity.
Ordinary physical activity does not cause
undue fatigue, palpitation, or dyspnea
(shortness of breath).
Class II (Mild)
Slight limitation of physical activity.
Comfortable at rest, but ordinary
physical activity results in fatigue,
palpitation, or dyspnea.
Class III (Moderate)
Marked limitation of physical activity.
Comfortable at rest, but less than
ordinary activity causes fatigue, palpitation, or dyspnea.
Class IV (Severe)
Unable to carry out any physical activity
without discomfort. Symptoms of
cardiac insufficiency at rest. If any
physical activity is undertaken, discomfort is increased.
PROGRESSION OF HEART FAILURE
Initially, the heart compensates by:
• Enlarging. When the heart enlarges, it can contract less
vigorously and still pump the same amount of blood.
• Developing more muscle mass. The increase in muscle mass
occurs because the contracting cells of the heart get bigger to
allow the heart chamber to enlarge.
• Increasing heart rate. The pump works more often to help
increase the heart's output.
These temporary measures initially mask the problem. However, heart failure often worsens until these compensation mechanisms cannot address the diminished contractile function of the
heart, and the patient may experience symptoms that prompt
medical consultation. This explains why some people may not
be aware of their condition until years after the heart muscle
begins its decline.5
Currently, there is no cure to halt or reverse the progression of heart
failure. However, treatments usually include lifestyle changes,
medicines and ongoing care. If the heart failure is at a severe stage,
medical procedures or surgery may be necessary. Heart failure
patients often require multiple medications to treat different
symptoms or contributing factors. Common medications to treat heart
failure are diuretics, beta blockers, ACE inhibitors, aldosterone antagonists, digoxin, angiotensin receptor blockers and isosorbide
dinitrate/hydralazine hydrochloride.1
Despite currently available therapies, readmission rates for heart
failure patients remain high. It is estimated that approximately 25% of
patients admitted to the hospital for heart failure will be readmitted
within 30 days.6 Mortality rates over the five-year period following a
diagnosis of heart failure are approximately 60% in men and 40% in
women.3 The high morbidity and mortality in the setting of current
therapies points to the need for novel therapeutics that offer further
reductions in morbidity and mortality.
ABOUT OMECAMTIV MECARBIL
In collaboration with Amgen, Cytokinetics is developing omecamtiv
mecarbil, a novel activator of cardiac myosin, the motor protein that
powers cardiac muscle contraction. It is an investigational drug
candidate designed to increase the duration of cardiac muscle contractility and improve cardiac muscle performance, potentially helping
patients preserve cardiac function and quality of life, avoid hospitalizations, and decrease the risk of mortality due to heart failure.
Omecamtiv mecarbil has been studied across nine Phase 1 clinical
trials, which enrolled over 200 healthy volunteers. In addition, more
than 1,300 people with heart failure have been enrolled in four
Phase 2 clinical trials, including COSMIC-HF. COSMIC-HF was a Phase 2
double-blind, randomized, placebo-controlled, multicenter, dose
escalation study, designed to evaluate the pharmacokinetics and
tolerability of orally-administered omecamtiv mecarbil in approximately 450 patients. The trial met its primary pharmacokinetic objective and
demonstrated statistically significant improvements in all pre-specified secondary measures of cardiac function in the treatment group
employing pharmacokinetic-based dose titration. Adverse events
(AEs), including serious AEs, in patients on omecamtiv mecarbil were
comparable to placebo. It is currently the subject of GALACTIC-HF, a
Phase 3 trial investigating the effects of omecamtiv mecarbil versus
placebo on cardiovascular outcomes in 8,000 patients, which is being
conducted by Amgen in collaboration with Cytokinetics.
References
1. National Heart, Lung and Blood Institute. What is Heart Failure?. Available at: http://www.nhlbi.nih.gov/health/dci/
Diseases/Hf/HF_WhatIs.html. Last revised: November 6, 2015. Accessed March 5, 2016.
2. Hall, MJ, et al. National hospital discharge survey: 2007 summary. Natl Health Stat Report. 2011; 29(29), 1-20.
Cytokinetics, Inc.
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cytokinetics.com
3. Roger, VL, et al. Heart disease and stroke statistics—2011 update a report from the American Heart Association.
Circulation. 2011; 123(4), e18-e209.
4. Centers for Disease Control and Prevention. Heart Failure Fact Sheet. Available at: http://www.cdc.gov/dhdsp/
data_statistics/fact_sheets/fs_heart_failure.htm. Last revised November 30, 2015. Accessed March 5, 2016.
5. American Heart Association. About Heart Failure. Available at: http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/About-Heart-Failure_UCM_002044_Article.jsp.Last revised April 6, 2015. Accessed March 5, 2016.
6. Krumholz, HM, et al. Patterns of hospital performance in acute myocardial infarction and heart failure 30-day mortality
and readmission. Circulation: Cardiovascular Quality and Outcomes. 2009; 2(5), 407-413.
Forward Looking Statements
This fact sheet 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; the design, results, timing and utility of the GALACTIC-HF clinical trial; 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 trial 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; and competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics' drug candidates and potential
drug candidates may target. For further information regarding these and other risks related to Cytokinetics' business, investors should consult Cytokinetics' filings with the Securities and Exchange
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