Cytokinetics Announces Positive Topline Results From MAPLE-HCM

Rhea-AI Summary

Cytokinetics (CYTK) announced positive topline results from MAPLE-HCM, a Phase 3 clinical trial comparing aficamten to metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The trial met its primary endpoint, showing statistically significant improvement in peak oxygen uptake (pVO2) from baseline to Week 24 for aficamten compared to the standard of care beta blocker metoprolol. The study involved 175 patients randomized 1:1 to receive either treatment as monotherapy. Aficamten demonstrated a favorable safety and tolerability profile compared to metoprolol. The trial design included patients with specific criteria including resting LVOT-G ≥30 mmHg and/or post-Valsalva LVOT-G ≥50 mmHg, with left ventricular ejection fraction ≥60%. Full results will be presented at an upcoming medical conference.

Positive

• Trial met primary endpoint showing superior efficacy of aficamten vs standard of care metoprolol
• Favorable safety and tolerability profile compared to metoprolol
• First evidence supporting aficamten's potential use as monotherapy for obstructive HCM

Negative

• None.

Insights

Cardiologist specializing in Hypertrophic Cardiomyopathy

Aficamten showed superior exercise capacity improvement versus metoprolol in obstructive HCM patients, potentially representing a paradigm shift in treatment.

The Phase 3 MAPLE-HCM trial results represent a significant breakthrough in obstructive hypertrophic cardiomyopathy treatment. Aficamten demonstrated statistically significant superiority to metoprolol on the critical endpoint of peak oxygen uptake (pVO2) at 24 weeks. This is remarkably important for HCM patients as pVO2 directly correlates with functional capacity and quality of life.

Current standard care relies on beta-blockers like metoprolol, which manage symptoms but have limitations including fatigue, exercise intolerance, and bronchospasm. As a cardiac myosin inhibitor, aficamten targets the underlying pathophysiology by directly reducing hypercontractility and outflow tract obstruction rather than merely addressing symptoms.

The trial design was particularly robust with 175 patients randomized 1:1, employing a double-blind, double-dummy methodology with careful stratification by exercise modality and disease chronicity. The meticulous washout period ensured clean comparison between treatments.

What's most clinically meaningful is this represents the first evidence for aficamten as monotherapy in obstructive HCM. The favorable safety profile compared to metoprolol is equally significant, as beta-blockers often limit patients' functionality. While full secondary endpoint data (KCCQ scores, NYHA class improvement, cardiac remodeling metrics) are pending, these positive results suggest aficamten could fundamentally transform HCM management by offering patients improved exercise capacity without the burden of beta-blocker side effects.

Trial Demonstrates Superiority of Aficamten to Standard of Care Beta Blocker in Improving Peak Exercise Capacity in Patients with Obstructive Hypertrophic Cardiomyopathy

SOUTH SAN FRANCISCO, Calif., May 13, 2025 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced positive topline results from MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), a Phase 3 clinical trial comparing aficamten as monotherapy to the standard of care beta blocker metoprolol as monotherapy in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

MAPLE-HCM met its primary endpoint, demonstrating a statistically significant improvement in peak oxygen uptake (pVO₂) from baseline to Week 24 for aficamten compared to metoprolol. The safety and tolerability profile of aficamten was favorable in comparison to metoprolol in MAPLE-HCM.

The full results from MAPLE-HCM will be presented at an upcoming medical conference.

“These results represent the first evidence that aficamten may be used as monotherapy to deliver clinically meaningful improvements in people living with obstructive hypertrophic cardiomyopathy,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “Importantly, the results from MAPLE-HCM provide important context to the benefit of this potential new medicine compared to the current standard of care. We are grateful to the investigators, site personnel and patients who participated in MAPLE-HCM, and look forward to presenting the full results at an upcoming medical meeting.”

MAPLE-HCM: Clinical Trial Design

MAPLE-HCM was a Phase 3, multi-center, randomized, double-blind active-comparator clinical trial of aficamten compared to metoprolol in patients with symptomatic obstructive HCM. The primary endpoint was the change in peak oxygen uptake (pVO₂) from baseline to Week 24 measured by cardiopulmonary exercise testing (CPET). Secondary endpoints include the change from baseline to Week 24 in Kansas City Cardiomyopathy Questionnaire (KCCQ) score, the proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class, and changes in left ventricular mass index (LVMI), left atrial volume index (LAVI), post-Valsalva left ventricular outflow tract gradient (LVOT-G) and NT-proBNP.

MAPLE-HCM enrolled 175 patients, randomized on a 1:1 basis to receive aficamten or metoprolol as monotherapy in a double-blind, double dummy fashion. Randomization was stratified by CPET exercise modality (treadmill or bicycle) and recently diagnosed versus chronic obstructive HCM. At screening, patients enrolled in MAPLE-HCM had a resting LVOT-G ≥30 mmHg and/or post-Valsalva LVOT-G ≥50 mmHg in addition to left ventricular ejection fraction (LVEF) ≥ 60%, respiratory exchange ratio (RER) ≥ 1.05 and pVO2 <100% predicted, NYHA functional class II or III and a KCCQ Clinical Summary Score (KCCQ-CSS) score ≥ 35 and ≤ 90. Following the initial screening visit, all participants on standard of care (SOC) therapy underwent a washout period of up to 14 days to wean from SOC therapy, followed by an additional 7 days with no SOC therapy prior to the second screening visit. Each patient received up to four escalating doses of aficamten or metoprolol based on echocardiographic guidance as well as a matching placebo for the alternate therapy.

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 compared to placebo in SEQUOIA-HCM, a positive pivotal Phase 3 clinical trial demonstrating improvements in functional capacity, LVOT gradients, and heart failure symptoms 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 by the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of December 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 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 Cytokinetics

Cytokinetics is a specialty cardiovascular biopharmaceutical company, building on its over 25 years of pioneering scientific innovations in muscle biology to advance a pipeline of potential new medicines for patients suffering from diseases of cardiac muscle dysfunction. Cytokinetics is readying for potential regulatory approvals and commercialization of aficamten, a 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.

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. 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.
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

What were the main results of Cytokinetics' (CYTK) MAPLE-HCM Phase 3 trial?

The MAPLE-HCM Phase 3 trial met its primary endpoint, showing statistically significant improvement in peak oxygen uptake (pVO2) from baseline to Week 24 for aficamten compared to metoprolol in patients with obstructive HCM.

How many patients participated in CYTK's MAPLE-HCM trial?

The MAPLE-HCM trial enrolled 175 patients, randomized 1:1 to receive either aficamten or metoprolol as monotherapy.

What is the significance of aficamten's results for Cytokinetics (CYTK)?

The results represent the first evidence that aficamten may be used as monotherapy for obstructive hypertrophic cardiomyopathy, demonstrating superiority to the current standard of care beta blocker.

What was the safety profile of CYTK's aficamten in the MAPLE-HCM trial?

Aficamten demonstrated a favorable safety and tolerability profile in comparison to metoprolol in the MAPLE-HCM trial.

What were the key enrollment criteria for Cytokinetics' MAPLE-HCM trial?

Patients needed resting LVOT-G ≥30 mmHg and/or post-Valsalva LVOT-G ≥50 mmHg, LVEF ≥60%, NYHA class II or III, and KCCQ-CSS score between 35 and 90.