Cytokinetics Announces European Medicines Agency Validation of Marketing Authorization Application for Aficamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy

Rhea-AI Summary

Cytokinetics (CYTK) announced that the European Medicines Agency (EMA) has validated their Marketing Authorization Application (MAA) for aficamten, a cardiac myosin inhibitor designed to treat obstructive hypertrophic cardiomyopathy (HCM). The application will be reviewed by the Committee for Medicinal Products for Human Use (CHMP).

The MAA is supported by results from the SEQUOIA-HCM Phase 3 clinical trial, published in the New England Journal of Medicine. This follows the FDA's acceptance of aficamten's New Drug Application (NDA) in the US, which has a PDUFA target action date of September 26, 2025. The drug is also under regulatory review in China.

Positive

• EMA validation of Marketing Authorization Application for aficamten represents expansion into European market
• Drug already under review in both US and China markets, indicating global market potential
• Phase 3 trial results published in prestigious New England Journal of Medicine

Negative

• Standard FDA review timeline (not priority) indicates longer path to potential US approval
• PDUFA date of September 26, 2025 suggests significant wait before potential revenue generation

Insights

Biotech Research Analyst

The EMA validation of aficamten's MAA represents a pivotal regulatory advancement for Cytokinetics. The drug's simultaneous review across three major markets (US, EU and China) positions it for potential global commercialization in obstructive hypertrophic cardiomyopathy (HCM), a condition affecting approximately 1 in 500 people worldwide.

The SEQUOIA-HCM trial results published in the prestigious New England Journal of Medicine lend strong credibility to the application. With the FDA's PDUFA date set for September 26, 2025 and the EMA review typically taking 12-14 months, Cytokinetics could potentially launch aficamten in major markets by late 2025 or early 2026.

The cardiac myosin inhibitor market for HCM, currently dominated by Bristol Myers Squibb's Camzyos, presents a substantial commercial opportunity estimated at $4+ billion annually. Aficamten's potential approval would make it only the second drug in its class, providing an alternative treatment option in this underserved market.

Market Research Analyst

This regulatory milestone significantly strengthens Cytokinetics' market position. With a $5.8B market cap, the company's valuation heavily relies on aficamten's success. The EMA validation, following US and Chinese regulatory submissions, demonstrates strong execution of their global commercialization strategy.

The timing is particularly strategic as it allows Cytokinetics to potentially establish market presence while the HCM treatment landscape is still developing. Early market research suggests that physicians are seeking alternatives to existing treatments and aficamten's next-in-class profile could capture significant market share.

For investors, this multi-market regulatory progress reduces geographic concentration risk and expands the total addressable market. The EU market alone represents approximately 30% of the global HCM opportunity, making this validation a important step toward realizing aficamten's full commercial potential.

SOUTH SAN FRANCISCO, Calif., Dec. 23, 2024 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for aficamten, a next-in-class cardiac myosin inhibitor, for the treatment of obstructive hypertrophic cardiomyopathy (HCM). The MAA will now be reviewed by the Committee for Medicinal Products for Human Use (CHMP).

“With regulatory filings for aficamten already under review in both the U.S. and China, the validation of the MAA marks an important milestone in bringing this potential medicine to even more patients with HCM worldwide,” said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. “We look forward to working with EMA in connection with their review of our application.”

The MAA 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 MAA validation follows the acceptance by the U.S. Food and Drug Administration (FDA) of the New Drug Application (NDA) for aficamten for the treatment of obstructive HCM. The FDA assigned the NDA a standard review with a Prescription Drug User Fee Act (PDUFA) target action date of September 26, 2025.

About SEQUOIA-HCM

SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) was the pivotal Phase 3 clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

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 [95% CI] of 1.74 mL/kg/min [1.04 - 2.44]; p=0.000002). Statistically significant improvements were observed in all 10 prespecified secondary endpoints, including Valsalva left ventricular outflow tract (LVOT) gradient, New York Heart Association (NYHA) Functional Class, Kansas City Cardiomyopathy Clinical Summary Score (KCCQ-CSS), and proportion with LVOT gradient <30 mmHg, each at 12 and 24 weeks, as well as duration of guideline eligibility for septal reduction therapy (SRT), and total workload during CPET at 24 weeks. Treatment emergent serious adverse events occurred in 5.6% and 9.3% of patients on aficamten and placebo, respectively. Core echocardiographic left ventricular ejection fraction (LVEF) was observed to be <50% in 5 patients (3.5%) on aficamten compared to 1 patient (0.7%) on placebo. There were no instances of worsening heart failure or treatment interruptions due to low LVEF.

Additional analyses from SEQUOIA-HCM have demonstrated that treatment with aficamten is associated with improvements in cardiac structure, function, and biomarkers without negatively impacting systolic function.

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. Cytokinetics is readying for the potential commercialization of aficamten, a 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 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:

1. Maron, MS, et al. Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy. N Engl J Med. DOI: 10.1056/NEJMoa2401424
2. 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
3. Symphony Health 2016-2021 Patient Claims Data DoF;
4. 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.
5. 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.
6. 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 FDA PDUFA date for Cytokinetics' (CYTK) aficamten?

The FDA has set a PDUFA target action date of September 26, 2025, for Cytokinetics' aficamten NDA for the treatment of obstructive HCM.

In which countries is CYTK's aficamten currently under regulatory review?

Aficamten is currently under regulatory review in the United States, China, and now the European Union following the EMA's MAA validation.

What clinical trial supports CYTK's European marketing application for aficamten?

The MAA is supported by results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial of aficamten in patients with symptomatic obstructive HCM.

What medical condition does CYTK's aficamten treat?

Aficamten is designed to treat obstructive hypertrophic cardiomyopathy (HCM), as a next-in-class cardiac myosin inhibitor.