Healthcare

Cytokinetics Presents New Data From REDWOOD-HCM OLE in

October 2, 2022

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Treatment with Aficamten Associated with Significant Improvements in Symptoms and Quality of Life

Additional Data Presented in Poster Session Shows Patients with Worsening Heart Failure and LVEF ≤30% Have Disproportionately High Risk of Heart Failure Hospitalization

SOUTH SAN FRANCISCO, Calif., Oct. 02, 2022 (GLOBE NEWSWIRE) — Cytokinetics, Incorporated (Nasdaq: CYTK) at this time introduced new information on symptom enchancment and high quality of life associated to remedy with aficamten in REDWOOD-HCM OLE (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM Open Label Extension) in a Late Breaking Clinical Trials session on the Heart Failure Society of America (HFSA) Annual Scientific Meeting in Washington, D.C.

Previously offered information from REDWOOD-HCM open label extension (OLE) confirmed that remedy with aficamten was related to important and sustained reductions in left ventricular outflow tract gradient (LVOT-G), enhancements in New York Heart Association (NYHA) Functional Class and enhancements in cardiac biomarkers.

This new evaluation evaluates sufferers’ self-reported well being standing utilizing the Kansas City Cardiomyopathy Questionnaire (KCCQ) and compares baseline values to these collected at Week 12 and Week 24. The KCCQ is a validated affected person reported outcomes instrument¹ used to guage coronary heart failure signs and their affect on social and bodily limitations in addition to high quality of life. Higher scores point out higher well being standing. As early as Week 12, sufferers skilled substantial and important symptom enhancements as measured by the change in their KCCQ scores. The KCCQ Overall Summary Score (KCCQ-OSS) and all KCCQ sub-domain scores demonstrated these enhancements, enhancements which had been additionally famous to be sustained by way of Week 24. At 12 and 24 weeks, the change from baseline (imply [SD]) change in KCCQ-OSS was 16.5 [16.7] (p<0.0001) and 17.6 [24.7] (p=0.0015). The proportion of sufferers with clinically necessary enhancements (enchancment ≥5 factors on the KCCQ-OSS) was 72.7% at Week 12 and 72.0% at Week 24, and 36.4% of sufferers at Week 12 and 40.0% at Week 24 reported a really massive scientific enchancment (≥20 factors). (Figure 1)

Figure 1

“These new data suggest that improvements in cardiac function associated with treatment with aficamten translate to patients reporting an overall improvement in their symptoms – particularly in their quality of life – which is of critical importance to patients with HCM who face a substantial symptom burden that impacts their daily lives.” mentioned Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “As REDWOOD-HCM OLE continues, aficamten is also under study in SEQUOIA-HCM, the Phase 3 registrational clinical trial in patients with obstructive HCM.”

Literature Synthesis Finds Patients with Worsening Heart Failure and LVEF ≤30% have Disproportionately High Risk of Heart Failure Hospitalization

In sufferers with coronary heart failure with diminished ejection fraction (HFrEF), earlier work has recognized that worsening coronary heart failure (WHF) and decrease left ventricular ejection fraction (LVEF) are threat components for cardiovascular (CV) dying and HF hospitalization. However, gaps stay in understanding the relative affect of those components. A brand new evaluation carried out in partnership with Yale University School of Medicine examined coronary heart failure prevalence and charges of hospitalization. Reported statistics and U.S. 2020 Census information had been used to estimate the prevalence of three teams of sufferers, together with these with coronary heart failure, these with HFrEF, and a 3rd higher-risk subgroup of sufferers with coronary heart failure with diminished ejection fraction with LVEF ≤30%. Among these teams, sufferers had been outlined as having worsening coronary heart failure if that they had a coronary heart failure occasion throughout the prior 6-12 months. Approximately 882 per 100,000 sufferers in the U.S. had been estimated to have HFrEF together with 634 per 100,000 with LVEF ≤30%. Within the HFrEF subgroup, 168 per 100,000 sufferers had worsening coronary heart failure, together with 126 per 100,000 with LVEF ≤30% and worsening coronary heart failure and (7% of all sufferers with coronary heart failure). Rates of coronary heart failure hospitalizations had been then estimated utilizing reported occasion charges. Among the 343 coronary heart failure hospitalizations per 100,000, 263 (76.7%) had been for sufferers with worsening coronary heart failure, suggesting that sufferers with worsening coronary heart failure have a disproportionately excessive threat of HF hospitalization. Furthermore, the higher-risk subgroup with each worsening coronary heart failure and LVEF ≤30% comprised 7% of sufferers with coronary heart failure, however accounted for 36% of all coronary heart failure hospitalizations (p<0.0001), an extra threat of 516% relative to the common affected person with coronary heart failure. This means that there stays important unmet medical want amongst folks with worsening coronary heart failure.

About Aficamten

Aficamten is an investigational selective, small molecule cardiac myosin inhibitor found following an in depth chemical optimization program that was carried out with cautious consideration to therapeutic index and pharmacokinetic properties and as could translate into next-in-class potential in scientific growth. Aficamten was designed to cut back the variety of lively actin-myosin cross bridges throughout every cardiac cycle and consequently suppress the myocardial hypercontractility that’s related to hypertrophic cardiomyopathy (HCM). In preclinical fashions, aficamten diminished myocardial contractility by binding on to cardiac myosin at a definite and selective allosteric binding web site, thereby stopping myosin from coming into a drive producing state. The growth program for aficamten is assessing its potential as a remedy that improves train capability and relieves signs in sufferers with HCM in addition to its long-term results on cardiac construction and performance. Aficamten acquired Breakthrough Therapy Designation for the remedy of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA).

About Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a illness in which the center muscle (myocardium) turns into abnormally thick (hypertrophied). The thickening of cardiac muscle results in the within of the left ventricle turning into smaller and stiffer, and thus the ventricle turns into much less in a position to calm down and fill with blood. This finally limits the center’s pumping perform, ensuing in signs together with chest ache, dizziness, shortness of breath, or fainting throughout bodily exercise. A subset of sufferers with HCM are at excessive threat of progressive illness which might result in atrial fibrillation, stroke and dying on account of arrhythmias. There aren’t any FDA accredited medical remedies that instantly handle the hypercontractility that underlies HCM.

About Heart Failure

Heart failure is a grievous situation that impacts greater than 64 million folks worldwide² about half of whom have diminished left ventricular perform.^3,4 It is the main reason behind hospitalization and readmission in folks age 65 and older.^5,6 Despite broad use of normal remedies and advances in care, the prognosis for sufferers with coronary heart failure is poor.⁷ An estimated one in 5 folks over the age of 40 are susceptible to growing coronary heart failure, and roughly 50 % of individuals identified with coronary heart failure will die inside 5 years of preliminary hospitalization.^8,9 More than 2 million folks in the U.S. are estimated to have an ejection fraction <30%, indicating they could have extreme coronary heart failure.¹⁰

About Cytokinetics

Cytokinetics is a late-stage biopharmaceutical firm targeted on discovering, growing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors as potential remedies for debilitating ailments in which muscle efficiency is compromised. As a pacesetter in muscle biology and the mechanics of muscle efficiency, the corporate is growing small molecule drug candidates particularly engineered to affect muscle perform and contractility. Cytokinetics is readying for the potential commercialization of omecamtiv mecarbil, its cardiac muscle activator, following constructive outcomes from GALACTIC-HF, a big, worldwide Phase 3 scientific trial in sufferers with coronary heart failure. Cytokinetics can also be growing aficamten, a next-generation cardiac myosin inhibitor, at the moment the topic of SEQUOIA-HCM, the Phase 3 scientific trial of aficamten in sufferers with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten can also be being evaluated in non-obstructive HCM in Cohort 4 of the Phase 2 scientific trial, REDWOOD-HCM. Cytokinetics can also be growing reldesemtiv, an investigational quick skeletal muscle troponin activator, at the moment the topic of COURAGE-ALS, a Phase 3 scientific trial in sufferers with amyotrophic lateral sclerosis (ALS). Cytokinetics continues its over 20-year historical past of pioneering innovation in muscle biology and associated pharmacology targeted to ailments of muscle dysfunction and circumstances of muscle weak point.

For extra details about Cytokinetics, go to www.cytokinetics.com and comply with us on Twitter, LinkedIn, Facebook and YouTube.

Forward-Looking Statements

This press launch accommodates forward-looking statements for functions of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to replace these forward-looking statements and claims the safety of the Act’s Safe Harbor for forward-looking statements. Examples of such statements, specific or implied, embrace, however aren’t restricted to, statements referring to the REDWOOD-HCM OLE or SEQUOIA-HCM scientific trial and statements referring to the potential advantages of aficamten for sufferers with obstructive or non-obstructive HCM or that remedy of sufferers with aficamten will forestall hospitalization. Cytokinetics’ analysis and growth actions; the design, timing, outcomes, significance and utility of preclinical and scientific outcomes; and the properties and potential advantages of Cytokinetics’ different drug candidates. Such statements are primarily based on administration’s present expectations, however precise outcomes could differ materially on account of numerous dangers and uncertainties, together with, however not restricted to, potential difficulties or delays in the event, testing, regulatory approvals for trial graduation, development or product sale or manufacturing, or manufacturing of Cytokinetics’ drug candidates that would sluggish or forestall scientific growth or product approval; Cytokinetics’ drug candidates could have hostile unwanted side effects or insufficient therapeutic efficacy; the FDA or overseas regulatory companies could delay or restrict Cytokinetics’ potential to conduct scientific trials; Cytokinetics could also be unable to acquire or preserve patent or commerce secret safety for its mental property; requirements of care could change, rendering Cytokinetics’ drug candidates out of date; and aggressive merchandise or various therapies could also be developed by others for the remedy of indications Cytokinetics’ drug candidates and potential drug candidates could goal. For additional info relating to these and different dangers associated to Cytokinetics’ business, traders ought to seek the advice of Cytokinetics’ filings with the Securities and Exchange Commission.

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