Cytokinetics Announces FDA Acceptance of New Drug Application for Aficamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy
Cytokinetics (CYTK) announced FDA acceptance of its New Drug Application (NDA) for aficamten, a cardiac myosin inhibitor for treating obstructive hypertrophic cardiomyopathy (HCM). The FDA set a PDUFA target date of September 26, 2025, with standard review and no planned advisory committee meeting.
The NDA is supported by SEQUOIA-HCM Phase 3 trial results, which showed significant improvement in exercise capacity with aficamten versus placebo. The drug demonstrated positive impacts on exercise capacity, clinical outcomes, and cardiac biomarkers, with statistically significant improvements in all 10 prespecified secondary endpoints. Treatment-emergent serious adverse events were lower in the aficamten group (5.6%) compared to placebo (9.3%).
Cytokinetics (CYTK) ha annunciato l'accettazione da parte della FDA della sua Domanda di Nuovo Farmaco (NDA) per aficamten, un inibitore della miosina cardiaca per il trattamento della cardiomiopatia ipertrofica ostruttiva (HCM). La FDA ha fissato una data obiettivo PDUFA per il 26 settembre 2025, con una revisione standard e senza incontri pianificati del comitato consultivo.
La NDA è supportata dai risultati dello studio clinico SEQUOIA-HCM Fase 3, che hanno mostrato un miglioramento significativo nella capacità di esercizio con aficamten rispetto al placebo. Il farmaco ha dimostrato impatti positivi sulla capacità di esercizio, sugli esiti clinici e sui biomarcatori cardiaci, con miglioramenti statisticamente significativi in tutti i 10 endpoint secondari prespecificati. Gli eventi avversi seri emergenti dal trattamento erano inferiori nel gruppo aficamten (5,6%) rispetto al placebo (9,3%).
Cytokinetics (CYTK) anunció la aceptación por parte de la FDA de su Solicitud de Nuevo Medicamento (NDA) para aficamten, un inhibidor de miosina cardíaca para el tratamiento de la cardiomiopatía hipertrófica obstructiva (HCM). La FDA estableció una fecha objetivo de PDUFA para el 26 de septiembre de 2025, con revisión estándar y sin reuniones planificadas del comité asesor.
La NDA está respaldada por los resultados del ensayo clínico de SEQUOIA-HCM Fase 3, que mostraron una mejora significativa en la capacidad de ejercicio con aficamten frente al placebo. El medicamento demostró impactos positivos en la capacidad de ejercicio, en los resultados clínicos y en los biomarcadores cardíacos, con mejoras estadísticamente significativas en los 10 puntos finales secundarios preespecificados. Los eventos adversos graves emergentes del tratamiento fueron menores en el grupo de aficamten (5,6%) en comparación con el placebo (9,3%).
사이토키네틱스(CYTK)는 아피캠텐의 새로운 약물 신청서(NDA)가 FDA의 승인을 받았다고 발표했습니다. 아피캠텐은 폐쇄성 비대 심근병증(HCM) 치료를 위한 심장 미오신 억제제입니다. FDA는 2025년 9월 26일을 PDUFA 목표 날짜로 설정하였으며, 표준 심사로 진행하며 자문위원회 회의는 계획되지 않았습니다.
NDA는 SEQUOIA-HCM 3상 임상 시험 결과에 의해 뒷받침되며, 아피캠텐이 위약 대비 운동 능력에서 상당한 개선을 보였음을 보여주었습니다. 이 약물은 운동 능력, 임상 결과 및 심장 바이오마커에 있어서 긍정적인 영향을 나타내었으며, 10개의 모든 사전 지정된 이차 평가변수에서 통계적으로 유의한 개선을 보였습니다. 치료 중 발생한 심각한 부작용은 아피캠텐 그룹(5.6%)에서 위약 그룹(9.3%)에 비해 낮았습니다.
Cytokinetics (CYTK) a annoncé l'acceptation par la FDA de sa Demande de Nouveau Médicament (NDA) pour aficamten, un inhibiteur de myosine cardiaque destiné au traitement de la cardiomyopathie hypertrophique obstructive (HCM). La FDA a fixé une date cible PDUFA au 26 septembre 2025, avec un examen standard et sans réunion du comité consultatif prévue.
La NDA est soutenue par les résultats de l'essai SEQUOIA-HCM Phase 3, qui ont montré une amélioration significative de la capacité d'exercice avec aficamten par rapport au placebo. Le médicament a démontré des impacts positifs sur la capacité d'exercice, les résultats cliniques et les biomarqueurs cardiaques, avec des améliorations statistiquement significatives dans les 10 points finaux secondaires prédéfinis. Les événements indésirables graves émergents du traitement étaient moins fréquents dans le groupe aficamten (5,6 %) par rapport au placebo (9,3 %).
Cytokinetics (CYTK) gab bekannt, dass die FDA ihren Antrag auf Zulassung eines neuen Arzneimittels (NDA) für aficamten angenommen hat, einen Hemmer der Herzmyosine zur Behandlung der obstruktiven hypertrophen Kardiomyopathie (HCM). Die FDA setzte ein PDUFA-Zieldatum auf den 26. September 2025, mit einer Standardprüfung und ohne geplante Beratungsausschusssitzung.
Das NDA wird durch die Ergebnisse der SEQUOIA-HCM Phase 3 Studie unterstützt, die eine signifikante Verbesserung der körperlichen Leistungsfähigkeit mit aficamten im Vergleich zum Placebo zeigten. Das Medikament zeigte positive Auswirkungen auf die körperliche Leistungsfähigkeit, klinische Ergebnisse und kardiale Biomarker, mit statistisch signifikanten Verbesserungen in allen 10 vordefinierten Sekundärendpunkten. Die behandlungsbedingten schwerwiegenden unerwünschten Ereignisse waren in der Aficamten-Gruppe (5,6 %) im Vergleich zur Placebo-Gruppe (9,3 %) geringer.
- FDA accepted NDA for aficamten with PDUFA date set
- Phase 3 SEQUOIA-HCM trial met primary endpoint with significant exercise capacity improvement
- All 10 secondary endpoints showed statistically significant improvements
- Lower rate of serious adverse events in treatment group (5.6%) vs placebo (9.3%)
- Previously received FDA Orphan Drug and Breakthrough Therapy Designations
- Standard review timeline rather than priority review
- Higher rate of left ventricular ejection fraction <50% in treatment group (3.5%) vs placebo (0.7%)
Insights
The FDA acceptance of aficamten's NDA represents a significant milestone in treating obstructive hypertrophic cardiomyopathy (HCM). The SEQUOIA-HCM Phase 3 trial demonstrated compelling efficacy with a
The September 26, 2025 PDUFA date could mark a significant advancement in HCM treatment. The absence of a planned advisory committee meeting suggests the FDA is comfortable with the data package. With both Orphan Drug and Breakthrough Therapy designations, aficamten could potentially capture substantial market share in the HCM space, particularly given its demonstrated cardiac remodeling benefits and positive impact on cardiac structure and function.
This regulatory milestone significantly derisks Cytokinetics' path to market for aficamten. With a market cap of
The lack of an advisory committee meeting is particularly bullish, suggesting a straightforward review process. The Breakthrough Therapy and Orphan Drug designations provide additional market advantages, including potential market exclusivity and expedited development pathways. If approved, aficamten could establish Cytokinetics as a major player in specialty cardiology, potentially driving significant revenue growth and market expansion.
PDUFA Target Action Date Set for September 26, 2025
SOUTH SAN FRANCISCO, Calif., Dec. 02, 2024 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that the U.S. Food & Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) for aficamten, a next-in-class cardiac myosin inhibitor, for the treatment of obstructive hypertrophic cardiomyopathy (HCM).
The FDA assigned the NDA a standard review with a Prescription Drug User Fee Act (PDUFA) target action date of September 26, 2025. The FDA is not currently planning to hold an advisory committee meeting to discuss the application.
“The NDA acceptance for aficamten by FDA is a significant milestone that moves our company another step closer to hopefully translating our pioneering science to the potential benefit of patients suffering from obstructive HCM. The results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial, which form the foundation of the NDA, demonstrated that aficamten has a positive impact on exercise capacity, clinical outcomes, symptom burden and cardiac biomarkers in patients with HCM, with a consistent effect across all prespecified subgroups and a favorable safety and tolerability profile,” said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. “If approved by FDA, we believe aficamten may expand utilization of cardiac myosin inhibitors and become the preferred choice amongst physicians and patients while also anchoring our emerging specialty cardiology franchise arising from Cytokinetics’ industry-leading muscle biology directed research.”
The NDA is supported by the results from SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), the pivotal Phase 3 clinical trial of aficamten in patients with symptomatic obstructive HCM, which were published in the New England Journal of Medicine.1
The results from SEQUOIA-HCM showed that treatment with aficamten for 24 weeks significantly improved exercise capacity compared to placebo, increasing peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) by 1.8 ml/kg/min compared to baseline in patients treated with aficamten versus 0.0 ml/kg/min in patients treated with placebo (least square mean (LSM) difference [
Additional analyses from SEQUOIA-HCM have demonstrated that treatment with aficamten is associated with favorable cardiac remodeling as well as improvements in cardiac structure, function, and biomarkers without negatively impacting systolic function.
The FDA previously granted aficamten Orphan Drug Designation for the treatment of symptomatic HCM in January 2021 and Breakthrough Therapy Designation for the treatment of obstructive HCM in December 2021.
About Aficamten
Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with HCM. In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state.
The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function. Aficamten was evaluated in SEQUOIA-HCM, a positive pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China where it is currently also under review for potential approval.
Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM; ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM; CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM; and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM.
About Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed, however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed in the U.S.2,3,4 Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn’t impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.5 People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes.6 A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation.
About Cytokinetics
Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing muscle biology-directed drug candidates as potential treatments for debilitating diseases in which cardiac muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact myocardial muscle function and contractility. Following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial evaluating aficamten, a next-in-class cardiac myosin inhibitor, in obstructive hypertrophic cardiomyopathy (HCM), Cytokinetics is progressing regulatory submissions for aficamten for the treatment of obstructive HCM in the US, Europe, and China. Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle 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 (FSTA) for the potential treatment of a specific type of muscular dystrophy.
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 properties or potential benefits of aficamten or any of our other drug candidates, our ability to obtain regulatory approval for aficamten for the treatment of obstructive hypertrophic cardiomyopathy or any other indication from FDA or any other regulatory body in the United States or abroad, and the labeling or post-marketing conditions that FDA or another regulatory body may require in connection with the approval of aficamten. 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 the risks related to Cytokinetics’ business outlines in Cytokinetics’ filings with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and Cytokinetics’ actual results of operations, financial condition and liquidity, and the development of the industry in which it operates, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that Cytokinetics makes in this press release speak only as of the date of this press release. Cytokinetics assumes no obligation to update its forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries.
Contact:
Cytokinetics
Diane Weiser
Senior Vice President, Corporate Affairs
(415) 290-7757
References:
- Maron, MS, et al. Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy. N Engl J Med. DOI: 10.1056/NEJMoa2401424
- CVrg: Heart Failure 2020-2029, p 44; Maron et al. 2013 DOI: 10.1016/S0140-6736(12)60397-3; Maron et al 2018 10.1056/NEJMra1710575
- Symphony Health 2016-2021 Patient Claims Data DoF;
- Maron MS, Hellawell JL, Lucove JC, Farzaneh-Far R, Olivotto I. Occurrence of Clinically Diagnosed Hypertrophic Cardiomyopathy in the United States. Am J Cardiol. 2016; 15;117(10):1651-1654.
- Gersh, B.J., Maron, B.J., Bonow, R.O., Dearani, J.A., Fifer, M.A., Link, M.S., et al. 2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Journal of the American College of Cardiology and Circulation, 58, e212-260.
- Hong Y, Su WW, Li X. Risk factors of sudden cardiac death in hypertrophic cardiomyopathy. Current Opinion in Cardiology. 2022 Jan 1;37(1):15-21
FAQ
When is the PDUFA date for Cytokinetics' (CYTK) aficamten NDA?
What were the main results of CYTK's SEQUOIA-HCM Phase 3 trial for aficamten?
What is the safety profile of CYTK's aficamten in the Phase 3 trial?
What regulatory designations has CYTK's aficamten received from the FDA?
