Cytokinetics Announces Five Presentations at the American College of Cardiology Annual Scientific Session & Expo
Cytokinetics (CYTK) announced five presentations about aficamten, their investigational cardiac myosin inhibitor for hypertrophic cardiomyopathy (HCM), at the upcoming American College of Cardiology Annual Scientific Session.
Key findings include:
- Drug metabolism study showed aficamten is eliminated through multiple CYP pathways: CYP2C9 (50%), CYP3A (26%), CYP2D6 (21%), and CYP2C19 (3%)
- Analysis of combination therapy with disopyramide showed good tolerability without enhanced LVOT gradient reduction compared to aficamten alone
- 72-week treatment data demonstrated significant improvements in cardiac structure and function, including reduced left ventricular mass index, wall thickness, and mitral regurgitation
- Placebo analysis revealed approximately one-third of KCCQ-OSS improvements were due to placebo effect
- Race/ethnicity study in non-obstructive HCM showed Black patients had higher rates of adverse cardiovascular outcomes compared to white patients
Cytokinetics (CYTK) ha annunciato cinque presentazioni riguardanti aficamten, il loro inibitore sperimentale della miosina cardiaca per la cardiomiopatia ipertrofica (HCM), alla prossima Sessione Scientifica Annuale del Collegio Americano di Cardiologia.
I risultati chiave includono:
- Lo studio sul metabolismo del farmaco ha mostrato che aficamten viene eliminato attraverso più vie CYP: CYP2C9 (50%), CYP3A (26%), CYP2D6 (21%) e CYP2C19 (3%)
- L'analisi della terapia combinata con disopiramide ha mostrato una buona tollerabilità senza una riduzione migliorata del gradiente LVOT rispetto ad aficamten da solo
- I dati del trattamento di 72 settimane hanno dimostrato significativi miglioramenti nella struttura e nella funzione cardiaca, inclusi la riduzione dell'indice di massa ventricolare sinistra, dello spessore della parete e della rigurgitazione mitralica
- L'analisi del placebo ha rivelato che circa un terzo dei miglioramenti del KCCQ-OSS erano dovuti all'effetto placebo
- Lo studio su razza/etnia nella HCM non ostruttiva ha mostrato che i pazienti neri avevano tassi più elevati di esiti cardiovascolari avversi rispetto ai pazienti bianchi
Cytokinetics (CYTK) anunció cinco presentaciones sobre aficamten, su inhibidor de miosina cardíaca en investigación para la cardiomiopatía hipertrófica (HCM), en la próxima Sesión Científica Anual del Colegio Americano de Cardiología.
Los hallazgos clave incluyen:
- El estudio de metabolismo del fármaco mostró que aficamten se elimina a través de múltiples vías CYP: CYP2C9 (50%), CYP3A (26%), CYP2D6 (21%) y CYP2C19 (3%)
- El análisis de la terapia combinada con disopiramida mostró una buena tolerabilidad sin una reducción mejorada del gradiente LVOT en comparación con aficamten solo
- Los datos de tratamiento de 72 semanas demostraron mejoras significativas en la estructura y función cardíaca, incluida la reducción del índice de masa ventricular izquierda, el grosor de la pared y la regurgitación mitral
- El análisis de placebo reveló que aproximadamente un tercio de las mejoras en KCCQ-OSS se debieron al efecto placebo
- El estudio de raza/etnicidad en HCM no obstructiva mostró que los pacientes negros tenían tasas más altas de resultados cardiovasculares adversos en comparación con los pacientes blancos
사이토키네틱스 (CYTK)는 하이퍼트로픽 심근병증 (HCM)을 위한 그들의 실험적 심장 미오신 억제제인 아피캄텐에 대한 다섯 가지 발표를 미국 심장학회 연례 과학 세션에서 발표한다고 발표했습니다.
주요 발견 사항은 다음과 같습니다:
- 약물 대사 연구에서 아피캄텐은 여러 CYP 경로를 통해 제거되는 것으로 나타났습니다: CYP2C9 (50%), CYP3A (26%), CYP2D6 (21%), CYP2C19 (3%)
- 디소피라미드와의 병용 요법 분석에서 아피캄텐 단독 요법에 비해 LVOT 경량 감소가 개선되지 않으면서도 좋은 내약성을 보였습니다
- 72주 치료 데이터는 좌심실 질량 지수, 벽 두께 및 승모판 역류 감소를 포함하여 심장 구조 및 기능에서 유의미한 개선을 보여주었습니다
- 플라시보 분석 결과 KCCQ-OSS 개선의 약 1/3이 플라시보 효과로 인한 것으로 나타났습니다
- 비폐쇄성 HCM에서의 인종/민족 연구는 흑인 환자들이 백인 환자들에 비해 부정적인 심혈관 결과 비율이 더 높다는 것을 보여주었습니다
Cytokinetics (CYTK) a annoncé cinq présentations sur l'aficamten, leur inhibiteur expérimental de myosine cardiaque pour la cardiomyopathie hypertrophique (HCM), lors de la prochaine Session Scientifique Annuelle du Collège Américain de Cardiologie.
Les résultats clés incluent:
- Une étude sur le métabolisme du médicament a montré que l'aficamten est éliminé par plusieurs voies CYP : CYP2C9 (50 %), CYP3A (26 %), CYP2D6 (21 %) et CYP2C19 (3 %)
- L'analyse de la thérapie combinée avec la disopyramide a montré une bonne tolérance sans réduction améliorée du gradient LVOT par rapport à l'aficamten seul
- Les données de traitement sur 72 semaines ont démontré des améliorations significatives de la structure et de la fonction cardiaques, y compris une réduction de l'indice de masse ventriculaire gauche, de l'épaisseur de la paroi et du reflux mitral
- L'analyse du placebo a révélé qu'environ un tiers des améliorations du KCCQ-OSS étaient dues à l'effet placebo
- Une étude sur la race/l'ethnicité dans l'HCM non obstructive a montré que les patients noirs avaient des taux plus élevés de résultats cardiovasculaires indésirables par rapport aux patients blancs
Cytokinetics (CYTK) gab fünf Präsentationen über Aficamten, ihren experimentellen kardialen Myosinhemmer für hypertrophe Kardiomyopathie (HCM), auf der bevorstehenden Jahrestagung der American College of Cardiology bekannt.
Wichtige Ergebnisse umfassen:
- Die Studie zum Arzneimittelmetabolismus zeigte, dass Aficamten über mehrere CYP-Wege eliminiert wird: CYP2C9 (50%), CYP3A (26%), CYP2D6 (21%) und CYP2C19 (3%)
- Die Analyse der Kombinationstherapie mit Disopyramid zeigte eine gute Verträglichkeit ohne eine verbesserte LVOT-Gradientenreduktion im Vergleich zu Aficamten allein
- Daten zur 72-wöchigen Behandlung zeigten signifikante Verbesserungen in der Herzstruktur und -funktion, einschließlich der Reduzierung des Linksventrikularen Massenindex, der Wanddicke und der Mitralinsuffizienz
- Die Placebo-Analyse ergab, dass etwa ein Drittel der KCCQ-OSS-Verbesserungen auf den Placebo-Effekt zurückzuführen war
- Die Studie zu Rasse/Ethnie bei nicht-obstruktiver HCM zeigte, dass schwarze Patienten im Vergleich zu weißen Patienten höhere Raten von unerwünschten kardiovaskulären Ergebnissen hatten
- Longer-term (72-week) treatment data shows significant improvements in cardiac structure and function
- Combination therapy with disopyramide demonstrated good safety profile
- Multiple metabolic pathways identified for drug elimination, reducing risk of drug-drug interactions
- Combination therapy with disopyramide showed no additional LVOT gradient reduction benefit
- One-third of patient-reported improvements attributed to placebo effect
- Significant racial disparities identified in treatment outcomes
Insights
Cytokinetics' upcoming presentations at the ACC conference provide meaningful clinical data that strengthen aficamten's profile in the competitive HCM treatment landscape. The five presentations collectively offer important insights into the drug's metabolism, safety profile, and long-term cardiac effects.
Most notably, the longer-term (48-72 week) cardiac structure data demonstrates statistically significant improvements in key measurements including left ventricular mass index (-9.8 g/m2), maximum left ventricular septal wall thickness (-2.4 mm), left atrial volume (-17.9 ml), and mitral regurgitant volume (-18.1 ml). These structural improvements suggest potential disease-modifying effects beyond symptomatic relief, which could differentiate aficamten commercially.
The metabolism findings showing multiple clearance pathways (CYP2C9 [
The safety data on combination therapy with disopyramide is reassuring, showing the drug was well-tolerated alongside current standard of care medication. This supports potential integration into existing treatment regimens upon approval.
The placebo effect analysis from SEQUOIA-HCM contextualizes the previously reported patient-reported outcomes, showing only one-third of improvement in the placebo arm was attributable to placebo effect itself.
These data points collectively enhance aficamten's clinical profile as the company progresses toward potential regulatory submissions and eventual commercialization.
New Analyses Related to Aficamten Expand on its Metabolism Pathways,
Treatment Effect Associated with Combination Therapy with Disopyramide
and Longer-Term Effect on Cardiac Structure and Function
SOUTH SAN FRANCISCO, Calif., March 17, 2025 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced five presentations related to aficamten, an investigational cardiac myosin inhibitor, and hypertrophic cardiomyopathy (HCM), at the American College of Cardiology (ACC) Annual Scientific Session & Expo taking place from March 29, 2025–March 31, 2025 in Chicago, IL.
“We are pleased to be sharing several new analyses relating to aficamten at the upcoming ACC Scientific Session & Expo,” said Stephen Heitner, M.D., Vice President, Head of Clinical Research. “The presentations describe the drug metabolism of aficamten, the safety of combination therapy with the standard of care medication disopyramide, and the effect of longer-term use of aficamten. Together these analyses add to the strong and growing evidence base supporting the potential for aficamten in patients with obstructive HCM and inform how it may be used in clinical practice.”
Evaluation of Cytochrome P450 2C9, 2C19, and 2D6 Inhibition on the Pharmacokinetics of Aficamten in Healthy Participants (1091-139)
Poster Presentation, March 29, 2025, 2:00-3:00 PM CT, South Hall. Neha Maharao, Ph.D., Senior Clinical Pharmacologist, Cytokinetics.
Data from an open-label, fixed-sequence drug-drug interaction (DDI) study of aficamten in healthy participants will be presented in a poster presentation. A previous study showed that aficamten is metabolized, in part, by the cytochrome P450 (CYP) enzyme 3A41. To further characterize its metabolic pathways, aficamten was evaluated with concomitant administration of three strong inhibitors of one or more of the CYP pathways: fluconazole (inhibitor of 2C9, 2C19, and 3A4), paroxetine (inhibitor of 2D6) and fluoxetine (inhibitor of 2C19 and 2D6). The data show that aficamten was eliminated by multiple CYP pathways, primarily by CYP2C9 (fraction metabolized [fm]=
Safety and Outcomes of Concomitant Aficamten and Disopyramide Use and Withdrawal in Patients with Obstructive Hypertrophic Cardiomyopathy: An Analysis of REDWOOD-HCM Cohort 3, SEQUOIA-HCM, and FOREST-HCM Trials (411-06)
Oral Presentation, March 31, 2025, 9:11-9:18 AM CT, S406b. Ahmad Masri, M.D., MS, Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University.
Data from an analysis of concomitant treatment with aficamten and disopyramide from completed and ongoing clinical trials of aficamten in patients with obstructive HCM will be presented in an oral presentation. The analysis included 50 participants from Cohort 3 of REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM), SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) and FOREST-HCM (Follow-up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM) who were receiving disopyramide at baseline. Participants were separated into four groups: those on disopyramide who underwent withdrawal of aficamten due to end of treatment in Cohort 3 of REDWOOD-HCM or SEQUOIA-HCM (n=29), patients on disopyramide receiving placebo in SEQUOIA-HCM (n=20), patients on aficamten who underwent disopyramide withdrawal in FOREST-HCM (n=17) and patients on aficamten who maintained treatment with disopyramide in FOREST-HCM (n=27). Combination therapy with aficamten and disopyramide was well-tolerated; the analysis suggests that combination of disopyramide with aficamten did not result in lower left ventricular outflow tract (LVOT) gradients compared to treatment with aficamten alone. The analysis suggests that withdrawal of disopyramide while receiving aficamten did not reduce the efficacy of aficamten and further that withdrawal of aficamten while on disopyramide resulted in the return of LVOT obstruction and symptoms, with an increase in NT-proBNP. There were no safety events reported with either aficamten or disopyramide withdrawal, and no episodes of atrial fibrillation after disopyramide withdrawal were reported.
Effect of Aficamten Treatment for Up to 72 Weeks on Cardiac Structure and Function in Patients with Obstructive Hypertrophic Cardiomyopathy: The SEQUOIA-HCM and FOREST-HCM CMR Sub-studies (964-09)
Moderated Poster Presentation, March 30, 2025, 12:06-12:13 PM CT, Theater 5. Ahmad Masri, M.D., MS, Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University.
New data from the cardiac magnetic resonance (CMR) imaging sub-studies of FOREST-HCM and SEQUOIA-HCM will be presented in a moderated poster presentation. At the time of the current analysis, 64 patients had completed a baseline CMR, including 36 patients who had completed a follow-up CMR at 72 weeks, and 28 patients who had completed a follow-up CMR at 48 weeks. Longer-term treatment with aficamten resulted in statistically significant improvements (mean ±SD) in measures of cardiac structure and function including left ventricular mass index (-9.8 g/m2 ±18.1, p<0.0001), maximum left ventricular septal wall thickness (-2.4 mm ±2.3, p<0.0001), left atrial volume (-17.9 ml ±28.3, p<0.0001) and mitral regurgitant volume (-18.1 ml ±19.2, p<0.0001) and fraction (-
Understanding the Impact of Placebo on Patient-Reported Health Status: An Analysis from SEQUOIA-HCM (1029-176)
Poster Presentation, March 29, 2025, 9:30-10:30 AM CT, South Hall. Charles F. Sherrod, M.D., M.Sc., Cardiology Fellow, UMKC Healthcare Institute for Innovations in Quality, Saint Luke’s Mid America Heart Institute.
A new analysis from SEQUOIA-HCM of the placebo effect on Kansas City Cardiomyopathy Questionnaire Overall Summary Scores (KCCQ-OSS) will be presented in a poster presentation. In patients randomized to placebo in SEQUOIA-HCM, the change in KCCQ-OSS was evaluated from baseline to Week 24 and following blinded treatment withdrawal from Week 24 to Week 28. Among the 140 (
Association Between Race/Ethnicity and Outcomes in Patients with Non-Obstructive Hypertrophic Cardiomyopathy (1251-173)
Poster Presentation, March 31, 2025, 10:30-11:30 AM CT, South Hall. Nosheen Reza, M.D., Assistant Professor of Medicine, Division of Cardiovascular Medicine, the Hospital of the University of Pennsylvania.
Data from a new health economics and outcomes research (HEOR) analysis of the association between race/ethnicity and outcomes in non-obstructive HCM patients will be presented in a poster presentation. This retrospective cohort study included adult patients diagnosed with non-obstructive HCM from January 1, 2013 to December 31, 2021. Of the 9,842 patients included,
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 as measured by peak oxygen uptake (pVO2) and relieves symptoms in patients with HCM. 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) and from the National Medical Products Administration (NMPA) in China.
Aficamten is currently under regulatory review in the U.S, where the FDA is reviewing a New Drug Application (NDA) for aficamten, which was assigned standard review a Prescription Drug User Fee Act (PDUFA) target action date of September 26, 2025. Additionally, the European Medicines Agency (EMA) is reviewing a Marketing Authorization Application (MAA) for aficamten, and The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) is reviewing an NDA for aficamten with Priority Review.
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 leading 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 pioneer in muscle 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 properties, treatment effect or potential benefits of aficamten or any of our other drug candidates or 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. 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.
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Cytokinetics
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References:
- Xu, D., Lutz, J., & Divanji, P., et al. (2024, March). Drug–Drug Interaction Study to Evaluate the Effect of Strong CYP3A Inhibition and P450 Induction on the Pharmacokinetics of Aficamten and the Effect of Aficamten on P-Glycoprotein in Healthy Participants. Poster session presented at the American Society for Clinical Pharmacology & Therapeutics Meeting, Colorado Springs, CO.
- 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
