Cytokinetics Announces Start of AMBER-HFpEF, a Phase 2 Clinical Trial of CK-586 in Patients With Symptomatic Heart Failure With Preserved Ejection Fraction
Cytokinetics (CYTK) has initiated AMBER-HFpEF, a Phase 2 clinical trial for CK-586 in patients with symptomatic heart failure with preserved ejection fraction (HFpEF). The study is designed as a randomized, placebo-controlled, double-blind, multi-center, dose-finding trial, specifically targeting patients with LVEF ≥60%.
CK-586, a cardiac myosin inhibitor, is being developed to treat a subgroup of HFpEF patients with hypercontractility and ventricular hypertrophy. The trial's focus on HFpEF patients is significant as approximately half of heart failure patients have this condition, characterized by ejection fraction ≥50%, impaired diastolic function, and elevated NTpro-BNP.
The development strategy builds on similarities between a subset of HFpEF patients and those with non-obstructive hypertrophic cardiomyopathy (nHCM), leveraging data from aficamten in nHCM.
Cytokinetics (CYTK) ha avviato AMBER-HFpEF, uno studio clinico di Fase 2 per CK-586 in pazienti con insufficienza cardiaca sintomatica con frazione d'eiezione preservata (HFpEF). Lo studio è progettato come un trial randomizzato, controllato con placebo, in doppio cieco, multicentrico e di ricerca di dosaggio, rivolto specificamente a pazienti con LVEF ≥60%.
CK-586, un inibitore della miosina cardiaca, è in fase di sviluppo per trattare un sottoinsieme di pazienti con HFpEF che presentano ipercontrattilità e ipertrofia ventricolare. Il focus del trial sui pazienti con HFpEF è significativo poiché circa metà dei pazienti con insufficienza cardiaca presenta questa condizione, caratterizzata da una frazione d'eiezione ≥50%, funzione diastolica compromessa e NTpro-BNP elevato.
La strategia di sviluppo si basa sulle somiglianze tra un sottoinsieme di pazienti con HFpEF e quelli con cardiomiopatia ipertrofica non ostruttiva (nHCM), sfruttando i dati su aficamten in nHCM.
Cytokinetics (CYTK) ha iniciado AMBER-HFpEF, un ensayo clínico de Fase 2 para CK-586 en pacientes con insuficiencia cardíaca sintomática con fracción de eyección preservada (HFpEF). El estudio está diseñado como un ensayo aleatorizado, controlado con placebo, doble ciego, multicéntrico y de búsqueda de dosis, dirigido específicamente a pacientes con LVEF ≥60%.
CK-586, un inhibidor de miosina cardíaca, se está desarrollando para tratar un subgrupo de pacientes con HFpEF que presentan hipercontractilidad e hipertrofia ventricular. El enfoque del ensayo en pacientes con HFpEF es significativo ya que aproximadamente la mitad de los pacientes con insuficiencia cardíaca tienen esta condición, caracterizada por una fracción de eyección ≥50%, función diastólica alterada y NTpro-BNP elevado.
La estrategia de desarrollo se basa en las similitudes entre un subconjunto de pacientes con HFpEF y aquellos con cardiomiopatía hipertrófica no obstructiva (nHCM), aprovechando los datos de aficamten en nHCM.
Cytokinetics (CYTK)는 보존된 박출 분율을 가진 증상성 심부전 환자에서 CK-586에 대한 2상 임상 시험인 AMBER-HFpEF를 시작했습니다. 이 연구는 LVEF ≥60%인 환자들을 대상으로 하는 무작위, 위약 대조, 이중 맹검, 다기관, 용량 탐색 시험으로 설계되었습니다.
CK-586은 심장 미오신 억제제로, 심부전 환자 중 과도한 수축력과 심실 비대를 가진 하위 집단을 치료하기 위해 개발되고 있습니다. HFpEF 환자에 대한 이 시험의 초점은 의미가 있으며, 심부전 환자의 약 절반이 박출 분율 ≥50%, 이완 기능 장애, NTpro-BNP 상승 등의 특징을 지닌 이 상태를 앓고 있기 때문입니다.
개발 전략은 HFpEF 환자 집단과 비폐쇄성 비대성 심근병증(nHCM) 환자 간의 유사성을 바탕으로 하며, nHCM에서 aficamten의 데이터를 활용하고 있습니다.
Cytokinetics (CYTK) a lancé AMBER-HFpEF, un essai clinique de phase 2 pour CK-586 chez des patients souffrant d'insuffisance cardiaque symptomatique avec fraction d'éjection préservée (HFpEF). L'étude est conçue comme un essai randomisé, contrôlé par placebo, en double aveugle, multicentrique et de recherche de dose, ciblant spécifiquement des patients avec LVEF ≥60%.
CK-586, un inhibiteur de myosine cardiaque, est en développement pour traiter un sous-groupe de patients HFpEF présentant une hypercontraction et une hypertrophie ventriculaire. L'accent mis par l'essai sur les patients HFpEF est significatif puisque près de la moitié des patients en insuffisance cardiaque présentent cette condition, caractérisée par une fraction d'éjection ≥50%, une fonction diastolique altérée et un NTpro-BNP élevé.
La stratégie de développement repose sur les similitudes entre un sous-ensemble de patients HFpEF et ceux atteints de cardiomyopathie hypertrophique non obstructive (nHCM), en s'appuyant sur les données d'aficamten dans le cadre de nHCM.
Cytokinetics (CYTK) hat AMBER-HFpEF initiiert, eine Phase-2-Studie für CK-586 bei Patienten mit symptomatischer Herzinsuffizienz mit erhaltener Ejektionsfraktion (HFpEF). Die Studie ist als randomisierte, placebo-kontrollierte, doppelt-blinde, multizentrische Dosierungsstudie konzipiert, die sich speziell an Patienten mit LVEF ≥60% richtet.
CK-586, ein Inhibitor von Kardio-Miosin, wird entwickelt, um eine Untergruppe von HFpEF-Patienten mit Hyperkontraktilität und ventrikulärer Hypertrophie zu behandeln. Der Fokus der Studie auf HFpEF-Patienten ist bedeutend, da ungefähr die Hälfte der Patienten mit Herzinsuffizienz diese Erkrankung aufweist, die durch eine Ejektionsfraktion ≥50%, beeinträchtigte diastolische Funktion und erhöhtes NTpro-BNP gekennzeichnet ist.
Die Entwicklungsstrategie baut auf den Ähnlichkeiten zwischen einer Untergruppe von HFpEF-Patienten und solchen mit nicht-obstruktiver hypertropher Kardiomyopathie (nHCM) auf und nutzt Daten von aficamten in nHCM.
- Advancement to Phase 2 clinical trial stage for CK-586
- Expansion into HFpEF market, which represents approximately 50% of heart failure patients
- Strategic alignment with existing data from aficamten in nHCM
- None.
Insights
The initiation of AMBER-HFpEF represents a strategic expansion of Cytokinetics' cardiac portfolio, specifically targeting a significant unmet medical need in heart failure treatment. The trial's focus on patients with HFpEF and LVEF ≥60% is particularly noteworthy, as it addresses a challenging subset of heart failure patients with therapeutic options.
The trial's design as a randomized, placebo-controlled, double-blind study strengthens its scientific validity. CK-586's mechanism as a cardiac myosin inhibitor is especially relevant for the target population, as these patients often present with hypercontractility and ventricular hypertrophy - similar characteristics to nHCM patients where Cytokinetics has shown success with aficamten.
For the general public: Think of the heart muscle in these patients as being too stiff and thick, like an overworked muscle. CK-586 aims to help the heart relax better, potentially improving how it functions. This trial is testing if this new drug can help patients whose hearts are pumping too forcefully, which might sound good but actually causes problems.
This Phase 2 trial initiation strengthens Cytokinetics' position in the specialty cardiology market. The company is cleverly leveraging its expertise in cardiac myosin modulation, expanding from its success with aficamten in nHCM to potentially address the HFpEF market - which represents approximately 50% of all heart failure cases.
The market opportunity is substantial, as HFpEF patients currently have treatment options and poor outcomes post-hospitalization. Success in this trial could position CK-586 as a pioneering therapy for a specific subset of HFpEF patients, potentially creating a new market segment within the broader heart failure treatment landscape.
For the general public: Imagine a company that's already good at making medicine for one heart problem, now using that knowledge to help patients with a similar but different heart condition. It's like expanding from making specialized running shoes for sprinters to making them for marathon runners - using the same expertise but reaching a new group of customers.
SOUTH SAN FRANCISCO, Calif., Jan. 21, 2025 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that AMBER-HFpEF (Assessment of CK-586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF) is open to enrollment. AMBER-HFpEF is a Phase 2 randomized, placebo-controlled, double-blind, multi-center, dose-finding clinical trial of CK-4021586 (CK-586) in patients with symptomatic heart failure with preserved ejection fraction (HFpEF) with left ventricular ejection fraction (LVEF) ≥
“We are pleased to be advancing CK-586 into a Phase 2 trial in a subset of patients with symptomatic HFpEF,” said Stuart Kupfer, M.D., Senior Vice President, Chief Medical Officer. “Despite recent advances in available treatments, patients with heart failure with supranormal ejection fraction continue to have a poor prognosis following hospitalization. Evaluating CK-586 in this Phase 2 trial further extends the potential of our cardiac myosin directed development platform focused to specialty cardiology indications.”
Approximately half of patients with heart failure have HFpEF, characterized by an ejection fraction of at least
About AMBER-HFpEF
AMBER-HFpEF is a Phase 2 randomized, placebo-controlled, double-blind, multi-center, dose-finding clinical trial in patients with symptomatic HFpEF with LVEF ≥
AMBER-HFpEF is planned to enroll approximately 60 patients randomized on a 3:1 basis to receive CK-586 or placebo in three dose escalation cohorts. Patients will receive up to two escalating doses of CK-586 over 12 weeks or placebo. An echocardiogram at Week 6 will determine whether patients will be up-titrated to the higher dose. Once-daily doses of 150 mg and 300 mg are planned in Cohort 1, 300 mg and 450 mg in Cohort 2 and 450 mg and 600 mg in Cohort 3. At screening, patients enrolled in AMBER-HFpEF must have LVEF ≥
About CK-4021586 (CK-586)
CK-4021586 (CK-586) is designed to be a novel, selective, oral, small molecule cardiac myosin inhibitor designed to reduce the hypercontractility associated with heart failure with preserved ejection fraction (HFpEF). CK-586 was designed to selectively inhibit the ATPase of intact cardiac myosin but does not inhibit the ATPase of subfragment-1 of myosin (S1). The inhibitory effect of CK-586 requires the presence of the regulatory light chain (RLC) of myosin in the context of the intact myosin dimer (heavy meromyosin or HMM). In preclinical models, CK-586 reduced cardiac hypercontractility by decreasing the number of active myosin cross-bridges during cardiac contraction thereby reducing the contractile force, without effect on calcium transients. In engineered human HCM heart tissues, CK-586 demonstrated shallow force-concentration response and improved lusitropy.
A subset of patients with HFpEF resemble patients with non-obstructive hypertrophic cardiomyopathy (nHCM) in that those patients have higher ejection fractions, thickened walls of their heart, elevated biomarkers, and symptoms of heart failure. Data from a Phase 2 clinical trial of aficamten, another investigational cardiac myosin inhibitor being developed by Cytokinetics, showed that in patients with nHCM aficamten was well tolerated, improved patient reported outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Functional Class) and biomarkers, measures that are also relevant to HFpEF. Aficamten was also well-tolerated with no drug discontinuations due to adverse events and no adverse events of heart failure. These data provide support for investigating this mechanism of action in HFpEF.
About Heart Failure with Preserved Ejection Fraction
Heart failure is a grievous condition that affects more than 64 million people worldwide.1 Approximately 6.7 million Americans have heart failure, which is expected to increase to over 8.5 million Americans by 2030.2 Approximately half of patients with heart failure have heart failure with preserved ejection fraction (HFpEF)3, and the prevalence of HFpEF is increasing.2,4 Approximately
About Cytokinetics
Cytokinetics is a late-stage, muscle biology specialty biopharmaceutical company focused on discovering, developing and commercializing muscle biology-directed drug candidates as potential treatments for debilitating diseases in which muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, Cytokinetics is intent on meaningfully improving the lives of patients through global access to innovative medicines. Cytokinetics is readying for potential regulatory approvals and commercialization of aficamten, a potential next-in-class cardiac myosin inhibitor following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy (HCM). Aficamten is also being evaluated in additional clinical trials enrolling patients with obstructive and non-obstructive HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac myosin activator, in patients with heart failure with severely reduced ejection fraction (HFrEF), CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten, for the potential treatment of heart failure with preserved ejection fraction (HFpEF) and CK-089, a fast skeletal muscle troponin activator with potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired skeletal muscle function.
For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, 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, express or implied, relating to the Company’s development plans for CK-586 in the United States, including its ability to full enroll AMBER-HFpEF by any particular date, if at all. 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' 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; 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 Commission.
CYTOKINETICS® and the C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries.
References:
- James et al. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018; 392: 1789–858.
- Bozkurt B, Ahmad T, Alexander KM, Baker WL, Bosak K, Breathett K, Fonarow GC, Heidenreich P, Ho JE, Hsich E, Ibrahim NE, Jones LM, Khan SS, Khazanie P, Koelling T, Krumholz HM, Khush KK, Lee C, Morris AA, Page RL 2nd, Pandey A, Piano MR, Stehlik J, Stevenson LW, Teerlink JR, Vaduganathan M, Ziaeian B; Writing Committee Members. Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America. J Card Fail. 2023 Oct;29(10):1412-1451. doi: 10.1016/j.cardfail.2023.07.006. Epub 2023 Sep 26. PMID: 37797885; PMCID: PMC10864030.
- Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail. 2012 Nov;5(6):720-6. doi: 10.1161/CIRCHEARTFAILURE.111.966366. Epub 2012 Aug 30. PMID: 22936826; PMCID: PMC3661289.
- 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.
- 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.
Contact:
Cytokinetics
Diane Weiser
Senior Vice President, Corporate Affairs
(415) 290-7757
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