A Phase 3, Open Label, Single Arm Study to Evaluate Efficacy, Safety and Tolerability of Aficamten in Adult Japanese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Researchers are looking for a better way to treat Japanese people who have symptomatic obstructive hypertrophic cardiomyopathy (symptomatic oHCM).
Obstructive hypertrophic cardiomyopathy (oHCM) is a type of heart disease where the heart muscles become thicker than normal due to over contraction. This thickening makes it harder than normal due to over contraction. This thickening makes it harder for the heart to pump blood out to the rest of the body. In symptomatic oHCM people with the condition experience symptoms like shortness of breath, chest pain, fainting, high blood pressure and irregular heartbeats.
The study treatment aficamten, also called BAY3723113, is under development to treat symptomatic oHCM. It aims to reduce the activity of cardiac myosin, a protein that helps heart muscles to contract, and thereby preventing over contraction and muscle thickening.
Although treatment options are available for symptomatic oHCM, there is still need for other treatment options that help target the root cause of the condition. In this study, researchers want to understand about the effects and long-term safety of aficamten in Japanese people with symptomatic oHCM.
The main purpose of the study is to learn how well aficamten works in Japanese with symptomatic oCHM.
For this, the researchers will check how participant's heart blood flow changes after 6 months of treatment. They do this by measuring the pressure needed for blood to leave the heart using a test called the left ventricular outflow tract (LVOT) gradient and a special breathing technique called Valsava maneuver.
Researchers will also look for:
* the number of participants who will have at least 1 level improvement on a scale doctors use to assess the effect of heart problems on daily activities after 3 and 6 months of treatment
* the change in the impact of heart problems on participant's daily lives based on their feedback on a questionnaire called Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) after 3 and 6 months of treatment.
This study will have 2 treatment periods: main treatment period and long-term treatment period. During the main treatment period, participants will take aficamten tablets once daily by mouth for up to 6 months. After completing this period, the participants who can join the long-term treatment period will continue taking aficamten until the drug becomes commercially available in Japan or the study ends.
Each participant will be in the study as long as they benefit from the treatment.
Participants will visit the study site:
* once before the treatment starts
* 9 times with a gap of 2 to 4 weeks between the visits during treatment under the main treatment period, and in the long-term treatment period, participants will visit almost every 3 months until the treatment ends.
* then 2 more times with a gap of 1 month between the visits after the treatment ends.
During the study, the study doctors and their team will:
* check participant's health by performing tests such as blood and urine tests, and checking heart health using an electrocardiogram (ECG) and echocardiogram (ECHO)
* ask the participants questions about how they are feeling and what adverse events are they having
An adverse event is any medical problem that a participant has during a study. Study doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatment. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study.
If the participant benefits from the treatment, treatment with aficamten after the end of the study might be possible.

Start Date20 Jun 2025

Sponsor / Collaborator

Bayer AG

NCT06412666

/ RecruitingPhase 2/3

A Phase 2/3 Multicenter, Randomized, Double-Blind, Placebo-Controlled and Open-Label Extension Trial to Evaluate the Efficacy and Safety of Aficamten in a Pediatric Population With Symptomatic Obstructive Hypertrophic Cardiomyopathy

The purpose of this study is to evaluate the efficacy, safety and PK of aficamten in a pediatric population with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).

Start Date29 May 2024

Sponsor / Collaborator

Cytokinetics, Inc.

NCT06116968

/ RecruitingPhase 3

An Open-Label Study of Aficamten for Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy

This is an open-label extension study of China cohort in the phase 3 study (CY 6031) of aficamten for the treatment of obstructive HCM (oHCM) to collect long-term safety and tolerability data, including assessments of cardiac function and steady-state Pharmacokinetics (PK) during chronic dosing with aficamten.

Start Date14 Nov 2023

Sponsor / Collaborator-

100 Clinical Results associated with Aficamten

100 Translational Medicine associated with Aficamten

100 Patents (Medical) associated with Aficamten

Literatures (Medical) associated with Aficamten

01 Aug 2025·JACC-Heart Failure

Aficamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy

Article

Author: Saberi, Sara ; Kupfer, Stuart ; Barriales-Villa, Roberto ; Oreziak, Artur ; Garcia-Pavia, Pablo ; Watkins, Hugh ; Masri, Ahmad ; Jacoby, Daniel L ; Coats, Caroline J ; Choudhury, Lubna ; Melloni, Chiara ; Fifer, Michael A ; Solomon, Scott D ; Abraham, Theodore P ; Tower-Rader, Albree ; Nassif, Michael E ; Heitner, Stephen B ; Elliott, Perry M ; Maron, Martin S ; Sherrid, Mark V ; Olivotto, Iacopo ; Meng, Lisa ; Rader, Florian ; Owens, Anjali T ; Malik, Fady I ; Wei, Jenny

BACKGROUND:

Long-term safety and efficacy data for aficamten in symptomatic obstructive hypertrophic cardiomyopathy are needed.

OBJECTIVES:

This study aims to evaluate 48-week experience from the ongoing FOREST-HCM (A Follow-Up, Open-Label, Research Evaluation of Sustained Treatment With Aficamten [CK-3773274] in Hypertrophic Cardiomyopathy) study.

METHODS:

Obstructive hypertrophic cardiomyopathy participants in an aficamten study (REDWOOD-HCM [Dose-finding Study to Evaluate the Safety, Tolerability, PK, and PD of CK-3773274 in Adults With HCM; NCT04219826]; SEQUOIA-HCM [Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT05186818]) could enroll in this phase 2/3, open-label, extension study. Participants received aficamten 5 mg once daily titrated ≤20 mg based on site-read echocardiographic assessments of Valsalva left ventricular outflow tract gradient and left ventricular ejection fraction.

RESULTS:

From May 2021 to October 2023, 213 participants enrolled; 46 participants with 48 weeks of follow-up were evaluated (mean age: 59.7 years; female: n = 26 [56.5%]). There were rapid, substantial, and sustained reductions in mean resting (-40 ± 34 mm Hg) and Valsalva peak left ventricular outflow tract gradient (-53 ± 39 mm Hg) from baseline to week 48. A total of 82% experienced ≥1 NYHA functional class improvement; 31% experienced a 20-point improvement in Kansas City Cardiomyopathy Questionnaire-Clinical Summary score. There were substantial reductions (mean change) in maximum left ventricular wall thickness (-1.2 ± 1.6 mm; P < 0.0001), left atrial volume index (-3.5 ± 6.6 mL/m²; P = 0.0008), lateral E/e' (-2.2 ± 6.1; P = 0.02), and cardiac biomarkers (P ≤ 0.0031). Aficamten was well tolerated with 2 (4.3%) asymptomatic and transient instances of left ventricular ejection fraction <50% (range: 47%-49%), neither resulting in drug discontinuation, and no new-onset atrial fibrillation.

CONCLUSIONS:

Aficamten treatment over 48 weeks was well tolerated and associated with substantial and durable relief of obstruction and symptom burden, lower cardiac biomarker levels, and cardiac phenotypic changes, which may indicate favorable cardiac remodeling. (A Follow-Up, Open-Label, Research Evaluation of Sustained Treatment With Aficamten [CK-3773274] in Hypertrophic Cardiomyopathy [FOREST-HCM]; NCT04848506).

01 Jul 2025·Cardiology in review

Aficamten—A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy

Review

Author: Aronow, Wilbert S. ; Frishman, William H. ; Naidu, Srihari S. ; Wang, Andy ; Patel, Jay

Hypertrophic cardiomyopathy is an under-recognized disease with a genetic component that results in abnormal and often asymmetric thickening of the left ventricle in addition to decreased compliance and progressive fibrosis of the myocardium. It further poses significant complications related to dynamic left ventricular outflow obstruction over time in a significant majority. The medical management of obstructive hypertrophic cardiomyopathy has evolved over the decades as our understanding has grown. Traditionally, the mainstay in management has included the use of various negative inotropic agents. In contrast, the cardiac myosin inhibitors, aficamten and mavacamten, are novel therapies targeting cardiac contractility at the sarcomere level that have demonstrated improvement in clinical outcomes for patients, and mavacamten (Bristol Myers Squibb, Inc.) has now been approved by the Food and Drug Administration for the treatment of symptomatic obstructive HCM. Aficamten (Cytokinetics, Inc.) is the second in class cardiac myosin inhibitor that is currently being evaluated in ongoing phase III clinical trials, and is the subject of this review.

01 Jun 2025·INTERNATIONAL JOURNAL OF TOXICOLOGY

A Characterization of the Nonclinical Pharmacology and Toxicology of Aficamten, a Reversible Allosteric Inhibitor of Cardiac Myosin

Article

Author: Wang, Jingying ; Chin, Eva R. ; Hwee, Darren T. ; Winters, Brett R. ; Malik, Fady I. ; Morgan, Bradley P. ; Pugsley, Michael K.

Aficamten (CK-3773274) is a cardiac myosin inhibitor in development for the treatment of hypertrophic cardiomyopathy (HCM), a commonly inherited heart condition often characterized as a disease of the sarcomere. Aficamten reduces pathologic cardiac hypercontractility by selectively binding to an allosteric site on cardiac myosin. To characterize the pharmacology and toxicology of aficamten, a series of nonclinical repeated dose studies were conducted. In a 10-day repeated dose pharmacology study in Sprague Dawley rats, aficamten produced dose-dependent reductions in left ventricular fractional shortening (FS) which were fully reversible within 24 h. Aficamten did not change the ratio of heart weight to tibia length (HW/TL) or left ventricular posterior wall (LVPW) thickness at any dose tested. At a supratherapeutic dose of 6 mg/kg/day, there was a significant increase in interventricular septum (IVS) thickness. Aficamten did not affect mRNA expression of the cardiac injury biomarkers BNP, β-MHC, or ANP. In repeated dose Good Laboratory Practice (GLP) regulatory toxicology studies in Sprague Dawley rats for up to 6 months and beagle dogs for up to 9 months, the primary adverse findings at supratherapeutic doses were consistent across all studies and observed in the heart consisting of atrial/ventricular dilatation that correlated with increased heart weights. These findings were largely reversible and consistent with excessive on-target pharmacology associated with cardiac myosin inhibition. The reversible nature of aficamten-associated adverse effects is supportive of its clinical safety as this property suggests that these findings, should they occur in humans, may also be reversible, limiting long-term human cardiac risk.

228

News (Medical) associated with Aficamten

18 May 2025

·ir.cytokinetics.com

Cytokinetics Presents Additional Data Related to Aficamten at the European Society of Cardiology Heart Failure 2025 Congress

Two New Analyses from SEQUOIA-HCM on Effect of Aficamten Between Patients with Mild and Moderate-to-Severe Symptoms, and Across Geographic Regions HEOR Analyses of Real-World Data Reveal Disparities in Outcomes In Females and Older Patients with Non-Obstructive HCM SOUTH SAN FRANCISCO, Calif., May 18, 2025 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that additional data arising from two analyses 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 hypertrophic cardiomyopathy (HCM), and results from a real-world analysis related to non-obstructive HCM were presented at the European Society of Cardiology Heart Failure 2025 Congress. The results from an analysis of the efficacy of aficamten in patients with obstructive HCM and mild symptoms in SEQUOIA-HCM were also simultaneously published in The European Heart Journal.1 “These analyses from SEQUOIA-HCM demonstrate that the effect of aficamten on exercise capacity, symptoms, hemodynamics and cardiac biomarkers is consistent in patients with obstructive HCM regardless of baseline symptom severity and geographic region,” said Stephen Heitner, M.D., Vice President, Head of Clinical Research. “These findings are informative as we continue to explore the potential application of aficamten across a range of patient phenotypes in obstructive HCM.” Effect of Aficamten in Patients with Mild Symptoms and Moderate-to-Severe Symptoms Data from an additional analysis from SEQUOIA-HCM related to the effect of aficamten in patients with mild symptoms were presented in a Late Breaking Clinical Trial session and simultaneously published in The European Heart Journal. Patients in SEQUOIA-HCM (n=282) were divided into two groups according to baseline symptom severity: mild symptoms, defined as New York Heart Association (NYHA) Functional Class II and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) ≥80 (n=118; 62 randomized to aficamten), and moderate-to-severe symptoms defined as NYHA Functional Class II/III/IV and KCCQ-CSS <80 (n=150; 71 randomized to aficamten). The effect of aficamten on the primary endpoint of change from baseline to Week 24 in peak oxygen uptake (pVO2) was similar between symptom groups (1.6 and 1.8 mL/kg/min in mild and moderate-to-severe symptom groups respectively; interaction p=0.8). While both groups experienced improvements in KCCQ-CSS, the magnitude of improvement was greater in the moderate-to-severe symptom group compared to the mild symptom group (interaction p=0.02) as expected given the lower baseline KCCQ-CSS score. At the end of the treatment period, 54% of patients with mild symptoms and 36% of patients with moderate-to-severe symptoms were asymptomatic. Additionally, more than half of patients in both groups had an improvement of at least one NYHA Functional Class (interaction p=0.6). Improvements in resting and Valsalva left ventricular outflow tract (LVOT) gradients and NT-proBNP also did not differ significantly between the two groups (all interaction p≥0.3). The safety and tolerability profile of aficamten was similar to placebo in both subgroups. These data indicate that, in SEQUOIA-HCM, the effect of aficamten was observed independent of baseline symptom burden in patients with obstructive HCM. Effect of Aficamten in Patients with Obstructive HCM Consistent Across Geographic Regions Data from an additional analysis from SEQUOIA-HCM evaluating geographical differences in the effect of aficamten were presented in a Late Breaking Clinical Trial session. Participants from SEQUOIA-HCM (n=282) were classified into three geographic regions: Europe, including Israel (n=142; 50%), North America (n=94; 33%) and China (n=46; 16%). At baseline, patients in Europe and North America were on average older, with a higher BMI, lower LVOT gradients, lower KCCQ-CSS and were more likely to have comorbidities than those in China. A greater proportion of patients in North America were NYHA Functional Class III/IV compared to Europe and China. Peak VO2, Valsalva LVOT gradient, NT-proBNP and hs-cardiac troponin I were similar across geographical regions. The distribution of doses of aficamten was similar across regions. The effect of aficamten on the primary endpoint of change in pVO2 and all secondary endpoints was consistent, with no significant differences across regions (all interaction p>0.15). The incidence of serious adverse events was similar in the aficamten and placebo groups across regions, and occurrences of left ventricular ejection fraction (LVEF) <50% were infrequent. These results demonstrate that in SEQUOIA-HCM, while there were regional differences in patient baseline characteristics, the dosing, safety profile and effect of aficamten was consistent across the geographic regions studied. Analyses of Real-World Data Reveal Association Between Age, Sex and Cardiovascular Outcomes in Patients with Non-Obstructive HCM Data presented from a health economics and outcomes research (HEOR) analysis evaluated the association between age, sex and cardiovascular outcomes in patients with non-obstructive HCM. This retrospective cohort study included adult patients diagnosed with non-obstructive HCM from January 1, 2013 to December 31, 2021 using real-world data from Optum Market Clarity database. Of the 9,842 patients included, 46.2% were female, 53.8% were male and the age distribution was as follows: 24.2% were ages 55 to 64 years, 22.1% were ages 75 or older, 22.1% were ages 65 to 74, 19.9% were ages 40 to 54 and 11.7% were ages 18 to 39. Female patients had increased rates of stroke (risk ratio [RR] 1.32), heart failure (RR 1.22), cardiovascular hospitalization (RR 1.23) and cardiovascular rehospitalization (RR 1.15) compared to male patients (all p<0.01). However, female patients were less likely to have atrial fibrillation (RR 0.83) and ventricular tachycardia (RR 0.69) (p<0.001). Compared to patients aged 75 years or older, younger patients were less likely to have atrial fibrillation, stroke, heart failure, cardiovascular hospitalization and cardiovascular rehospitalization (all p<0.001). All-cause mortality was significantly greater in female patients compared to male patients (p=0.002). Patients aged 75 years or older had the highest all-cause mortality (16.6%; p<0.001), followed by patients aged 65 to 74 (8.3%), 55 to 64 (3.5%), 40 to 54 (3.1%) and 18 to 39 years (1.4%). These findings highlight disparities in morbidity and survival among females and older patients with non-obstructive HCM, emphasizing the potential role for novel treatments to help reduce the clinical burden. 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.2 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 symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic HCM from the U.S. Food & Drug Administration (FDA) and for the treatment of symptomatic obstructive HCM from the National Medical Products Administration (NMPA) in China. 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. This communication contains a summary of new data related to the clinical development of aficamten presented at the European Society of Cardiology Heart Failure 2025 Congress. Aficamten is an investigational drug and is not approved by any regulatory agency. Its safety and efficacy have not been established. Aficamten is currently under regulatory review in the U.S, where the FDA is reviewing a New Drug Application (NDA) for aficamten 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. 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.3,4,5 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.6 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.7 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 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 by any particular date, if ever. 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: Source: Cytokinetics, Incorporated

Phase 3Clinical ResultNDABreakthrough TherapyPriority Review

15 May 2025

·pmlive.com

Cytokinetics shares positive phase 3 results for aficamten in heart disease

Cytokinetics has shared positive top-line results from a late-stage study of its investigational oral cardiac myosin inhibitor aficamten in hypertrophic cardiomyopathy (HCM). The phase 3 MAPLE-HCM trial has been comparing the candidate against standard-of-care beta blocker metoprolol in more than 170 patients with symptomatic obstructive HCM. As many as one in 500 people in the UK and US are living with HCM, a common form of genetic heart disease. Some patients do not experience symptoms, causing a large percentage of cases to remain undiagnosed, while others may only feel symptoms such chest pain and shortness of breath during exercise. Approximately two-third of HCM patients have the obstructive form of the condition, in which the thickened part of the heart muscle blocks or reduces the blood flow from the heart, while non-obstructive HCM, when the heart muscle is thickened but does not block blood flow out of the heart, is less common. Aficamten is designed to reduce the hypercontractility associated with HCM by blocking myosin, a motor protein that plays a key role in muscle contraction, from pulling. MAPLE-HCM met its primary endpoint, with aficamten monotherapy significantly improving peak oxygen uptake, measured by cardiopulmonary exercise testing, compared to metoprolol monotherapy from baseline to week 24. The safety and tolerability profile of Cytokinetics’ drug was also shown to be favourable in comparison to metoprolol. The company’s executive vice president of research and development, Fady Malik, said the results “represent the first evidence that aficamten may be used as monotherapy to deliver clinically meaningful improvements in people living with obstructive HCM”. “Importantly, the results from MAPLE-HCM provide important context to the benefit of this potential new medicine compared to the current standard of care,” he added. Aficamten, which is also being evaluated in non-obstructive HCM, is currently under regulatory review by the US Food and Drug Administration, with a decision expected by 26 December. The drug is also being assessed by the European Medicines Agency.

Phase 3Clinical ResultNDA

14 May 2025

·www.globenewswire.com

Cytokinetics Announces Positive Topline Results From MAPLE-HCM

Trial Demonstrates Superiority of Aficamten to Standard of Care Beta Blocker in Improving Peak Exercise Capacity in Patients with Obstructive Hypertrophic Cardiomyopathy May 13, 2025 -- 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 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 aficamten or metoprolol based on echocardiographic guidance as well as a matching placebo for the alternate therapy. 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. 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. 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 The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultNDABreakthrough TherapyPriority Review

100 Deals associated with Aficamten

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertrophic obstructive cardiomyopathy	NDA/BLA	China	Cytokinetics, Inc.	15 Oct 2024
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	United States	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	China	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Argentina	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Australia	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Brazil	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Canada	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Denmark	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	France	Cytokinetics, Inc.	30 Aug 2023
Hypertrophic Cardiomyopathy without Obstruction	Phase 3	Germany	Cytokinetics, Inc.	30 Aug 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05767346 (MAPLE-HCM, GlobeNewswire \| NEWS) Manual	Phase 3	Hypertrophic obstructive cardiomyopathy	-	Aficamten	nvycjirpuu(pkzdlcmtzt) = 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. jchzjzozat (mtgvfzxwpq ) Met	Positive	13 May 2025
				Metoprolol
NCT05186818 (SEQUOIA-HCM, GlobeNewswire) Manual	Phase 3	Cardiomyopathy, Hypertrophic	-	Aficamten	clkandggax(uluicqzonk) = bgfsmhovsy dkifobewnf (invyhkalls, 3.1) View more	Positive	16 Nov 2024
				Placebo	clkandggax(uluicqzonk) = xgykyqbnls dkifobewnf (invyhkalls, 2.7) View more
NCT05186818 (SEQUOIA-HCM, Pubmed \| J Am Coll Cardiol)	Phase 3	Hypertrophic obstructive cardiomyopathy N-terminal pro-B-type natriuretic peptide	-	Aficamten	tlcmgqvdtm(qkgjmcthyx) = mhtpaertkp jnpzypnceg (amrtwcyhth ) View more	Positive	01 Nov 2024
				Placebo	tlcmgqvdtm(qkgjmcthyx) = egjhonhxik jnpzypnceg (amrtwcyhth ) View more
NCT05186818 (SEQUOIA-HCM, Pubmed \| J Am Coll Cardiol)	Phase 3	Hypertrophic obstructive cardiomyopathy	282	Aficamten	iufburtgce(pmsvxijiki) = odymbpgtao fbtuckygjy (pfycebauvz, -25 to -6) View more	Positive	01 Nov 2024
NCT05186818 (SEQUOIA-HCM, Pubmed \| J Am Coll Cardiol)	Phase 3	Hypertrophic obstructive cardiomyopathy N-terminal pro-B-type natriuretic peptide (NT-proBNP)	282	Aficamten	iycciaqrhk(fjxcngbqco) = uoechohfai dbxlnumbcd (pixqrvtzyj ) View more	Positive	01 Nov 2024
NCT04219826 \| NCT04848506 \| NCT05186818 (FOREST-HCM, GlobeNewswire) Manual	Phase 2/3	Cardiomyopathy, Hypertrophic	-	Aficamtenaficamten (Cumulative aficamten-treated pool)	mgvalzltnq(bynjxnszum) = ibcrtmdlol worxthxsxe (trhqzuwuno ) View more	Positive	01 Sep 2024
				Aficamten (Placebo-controlled pool)	mgvalzltnq(bynjxnszum) = nlnzksgdhc worxthxsxe (trhqzuwuno ) View more
NCT05186818 (SEQUOIA-HCM, GlobeNewswire) Manual	Phase 3	Cardiomyopathy, Hypertrophic	282	Aficamten	qzbumjkrfz(xybsozcfqe): Difference = -12.2 (95% CI, -18.0 to -6.5), P-Value = <0.001 View more	Positive	01 Sep 2024
				Placebo
NCT04219826 \| NCT04848506 \| NCT05186818 (ESC2024)	Not Applicable	Hypertrophic obstructive cardiomyopathy	-	Aficamten	llrrptwytl(ihdlmfzcvp) = awwcrvghdv njbhaxzkkq (bxgjeaxuza ) View more	-	01 Sep 2024
				Placebo	llrrptwytl(ihdlmfzcvp) = uwlldbrdek njbhaxzkkq (bxgjeaxuza ) View more
NCT05186818 (SEQUOIA-HCM, Pubmed) Manual	Phase 3	Hypertrophic obstructive cardiomyopathy	282	aficamten	pyggzvttvs(tjrkmntyql) = ygjmhjftrf hfefwlvklk (vukfmdozfu, 1.2 - 2.3) Met View more	Positive	13 May 2024
NCT04848506 (FOREST-HCM, Corporate Publications) Manual	Phase 2	Cardiomyopathy, Hypertrophic	46	Aficamten	fgvanvksfp(wadimvvabp) = none zrcdzwminv (tsihqthvet ) View more	Positive	05 Apr 2024

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