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-

NCT06081894

/ RecruitingPhase 3

A Phase 3, Multi-Center, Randomized, Double-Blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

This clinical trial will study the effects of aficamten (versus placebo) on the quality of life, exercise capacity, and clinical outcomes of patients with non-obstructive hypertrophic cardiomyopathy.

Start Date30 Aug 2023

Sponsor / Collaborator

Cytokinetics, Inc.

[+2]

100 Clinical Results associated with Aficamten

100 Translational Medicine associated with Aficamten

100 Patents (Medical) associated with Aficamten

Literatures (Medical) associated with Aficamten

01 May 2025·American heart journal plus : cardiology research and practice

Efficacy of aficamten in obstructive hypertrophic cardiomyopathy: A systematic review and meta-analysis

Review

Author: Irfan, Hamza ; Safiullah, Muhammad ; Javaid, Hammad ; Haq, Muhammad Zain Ul ; Fatima, Laveeza ; Saddique, Muhammad Nabeel ; Iqbal, Javed ; Ashraf, Saad ; Bhatti, Muhammad Imaz ; Masood, Saad ; Qadri, Maria ; Jha, Anurag ; Mehmood, Qasim ; Iftikhar, Sana ; Shamoon, Sheena

Background:

Obstructive hypertrophic cardiomyopathy (oHCM), a morbid hereditary condition, is characterized by asymmetrical intraventricular septum enlargement, obstructing blood flow from the left ventricle outflow tract (LVOT) and lowering cardiac output. Aficamten, a novel selective, oral myosin inhibitor, has been suggested to reduce myocardial hypercontractility and decrease LVOT gradient in oHCM.

Methods:

A comprehensive search was conducted through PubMed, Embase, Scopus, and Cochrane databases for relevant literature from inception up to May 2024. Six studies focusing on efficacy and safety aficamten was included. Pooled outcome estimates were reported as mean difference (MD) and 95 % CI using random effect model. Statistical heterogeneity was assessed using I² and X² statistics.

Results:

We found a significant change of -143.23 (pg/ml) NT-proBNP [95 % CI -564.8 to 278.4, I² = 97.65 %, P < 0.001], -50.9 mmHg Valsalva LVOT gradient [95 % CI -55.2 to -46.6, I² = 0 %, P = 0.44], -38.5 mmHg resting LVOT gradient [95 % CI -49.9 to -27.6, I² = 0 %, P = 0.64], -5.98 % mean LVEF [95 % CI -9.4 to -2.6, I² = 64.18 %, P = 0.06] and -2.32 (ng/dl) Hs-Troponin I [95 % CI -7.55 to -2.91, I² = 0 %, P = 0.97] from the baseline. We found significant 64.9 % ≥ 1 NYHA class improvement [95 % CI 45.8 %-84.1 %, I² = 90.6 %, P < 0.001] in aficamten. There was 'low' overall risk of bias in included studies.

Conclusion:

We found that aficamten significantly reduced myocardial stress surrogates and functional disability parameters. The small sample sizes, diverse study designs and single-arm analysis limit our findings. More robust trials with larger sample sizes are required to establish conclusive evidence.

01 May 2025·American Journal of Cardiovascular Drugs

Cardiac Myosin Inhibitors for Obstructive Hypertrophic Cardiomyopathy: A Meta-analysis of Randomized Placebo-Controlled Trials

Review

Author: Alexandre, Felipe Kalil Beirão ; Kherallah, Riyad Yazan ; Felix, Nicole ; Alexandre Costa, Thomaz ; Nogueira, Alleh ; Serpa, Frans ; Andrade Duarte de Farias, Maria do Carmo ; Godoi, Amanda ; Vianna Silva, Guilherme ; Pirez, Jacqueline ; Teixeira, Larissa

BACKGROUND:

Cardiac myosin inhibitors (CMI) have emerged as the first disease-specific, noninvasive therapy with promising results in patients with hypertrophic cardiomyopathy. However, its role in obstructive hypertrophic cardiomyopathy (oHCM) remains uncertain, especially in secondary endpoints of randomized controlled trials (RCTs).

METHODS:

We systematically searched PubMed, Embase, Web of Science, and Clinicaltrials.gov from inception to June 2024 for RCTs comparing CMI versus placebo in patients with oHCM. We applied a random-effects model to evaluate efficacy and safety outcomes and primary or secondary outcomes of RCTs.

RESULTS:

We included five RCTs comprising 767 patients, of whom 402 (52.5%) were randomized to CMI. Relative to placebo, CMI were associated with a higher rate of improvement of at least one New York Heart Association (NYHA) functional class [risk ratio (RR) 2.33; 95% confidence interval (CI) 1.92-2.82]. In addition, CMI reduced resting left ventricular outflow tract (LVOT) [mean difference (MD) - 42.51 mmHg; 95% CI - 59.27 to - 25.75] and the provoked LVOT gradients (MD - 46.12 mmHg; 95% CI - 55.70 to - 36.54). However, CMI significantly increased the risk of reaching a left ventricular ejection fraction below 50% (RR 4.80; 95% CI 1.42-16.20), affecting 8% of patients during long-term follow-up of up to 120 weeks. There was no significant interaction across subgroups of class representatives, pointing to a class effect. The benefit-risk analysis indicated a larger benefit for NYHA class improvement than risk for systolic dysfunction.

CONCLUSION:

In patients with oHCM, mavacamten and aficamten as a class improve clinical and hemodynamic endpoints compared with placebo, albeit with a higher incidence of a reduction in left ventricular ejection fraction.

REGISTRATION:

PROSPERO CRD42023468079.

01 May 2025·JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA

Advances in Cardiovascular Pharmacotherapy. I. Cardiac Myosin Inhibitors

Review

Author: Crystal, George J ; Pagel, Paul S ; Freed, Julie K ; Hang, Dustin

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. The disease is characterized by asymmetric left ventricular (LV) remodeling with myocyte disarray and interstitial fibrosis, a hypercontractile state, dynamic subaortic obstruction of the LV outflow tract, impaired LV diastolic function, atrial and ventricular arrhythmias, and sudden cardiac death. HCM occurs as a result of pathological alterations in the cardiac myocyte's chemomechanical cycle, in which an enhanced rate of myosin-actin crossbridge formation and destabilization of the energy-conserving "super-relaxed off-actin state" of myosin play essential roles. For decades, management of HCM has been limited almost exclusively to medications (eg, beta-blockers, calcium channel blockers, disopyramide) and interventions (eg, septal reduction therapy, implanted cardioverter-defibrillator devices) that palliate symptoms, but do not address the disease's underlying causative mechanisms. A new class of cardiovascular medications, cardiac myosin inhibitors, has surged to the forefront of HCM treatment in recent years. These drugs, including mavacamten and aficamten, show great promise to profoundly affect the disease's clinical course. In this article, the authors review the molecular mechanisms of action of cardiac myosin inhibitors, discuss in detail the most recent data from mavacamten and aficamten clinical trials, describe future planned studies designed to address unanswered questions about their clinical utility in HCM phenotypes, and comment on their potential application to patients with other forms of heart failure with preserved ejection fraction. The possible anesthetic implications of mavacamten and aficamten are also discussed because it is highly likely that patients who are treated with these medications will begin to present for perioperative care with increasing regularity.

227

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

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05767346 (MAPLE-HCM, GlobeNewswire \| NEWS) Manual	Phase 3	Hypertrophic obstructive cardiomyopathy	-	Aficamten	ezxmaeofzo(bgmnjuxatn) = 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. nasqicryna (fgesevlbxm ) Met	Positive	13 May 2025
				Metoprolol
NCT05186818 (SEQUOIA-HCM, GlobeNewswire) Manual	Phase 3	Cardiomyopathy, Hypertrophic	-	Aficamten	wrupgkmhoh(kjnoaonbpk) = hvidyjxqnn ujdwlpibsv (benhtwpbwd, 3.1) View more	Positive	16 Nov 2024
				Placebo	wrupgkmhoh(kjnoaonbpk) = bgpdcpvigi ujdwlpibsv (benhtwpbwd, 2.7) View more
NCT05186818 (SEQUOIA-HCM, Pubmed \| J Am Coll Cardiol)	Phase 3	Hypertrophic obstructive cardiomyopathy N-terminal pro-B-type natriuretic peptide (NT-proBNP)	282	Aficamten	zwyzozmfdh(iffidluhaa) = fwixyfggij pcrbatotzl (wjvdroasmy ) View more	Positive	01 Nov 2024
NCT05186818 (SEQUOIA-HCM, Pubmed \| J Am Coll Cardiol)	Phase 3	Hypertrophic obstructive cardiomyopathy	282	Aficamten	cttvycyuqf(fjhsgeelys) = wmourxrjka arybzdcxxn (glznrxlqjo, -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	-	Aficamten	bkjguihbqz(pqvizalshr) = irepxpmvjb unhzioziac (zhnikgwpxi ) View more	Positive	01 Nov 2024
				Placebo	bkjguihbqz(pqvizalshr) = gdkjhhjfke unhzioziac (zhnikgwpxi ) View more
NCT05186818 (SEQUOIA-HCM, GlobeNewswire) Manual	Phase 3	Cardiomyopathy, Hypertrophic	282	Aficamten	bmeikjfyzi(fxfamqdcva): Difference = -12.2 (95% CI, -18.0 to -6.5), P-Value = <0.001 View more	Positive	01 Sep 2024
				Placebo
NCT04219826 \| NCT04848506 \| NCT05186818 (FOREST-HCM, GlobeNewswire) Manual	Phase 2/3	Cardiomyopathy, Hypertrophic	-	Aficamtenaficamten (Cumulative aficamten-treated pool)	vqkxaysnfs(ygshmkarnc) = xhcvstkrxe syxflnhnyy (uqjqukcajr ) View more	Positive	01 Sep 2024
				Aficamten (Placebo-controlled pool)	vqkxaysnfs(ygshmkarnc) = odfxoncpji syxflnhnyy (uqjqukcajr ) View more
NCT04219826 \| NCT04848506 \| NCT05186818 (ESC2024)	Not Applicable	Hypertrophic obstructive cardiomyopathy	-	Aficamten	rfmvtdfppq(oemlycjgju) = ajrxeyhzsv gosymhagzs (jmilheohxl ) View more	-	01 Sep 2024
				Placebo	rfmvtdfppq(oemlycjgju) = iqdtjpihku gosymhagzs (jmilheohxl ) View more
NCT05186818 (SEQUOIA-HCM, Pubmed) Manual	Phase 3	Hypertrophic obstructive cardiomyopathy	282	aficamten	myxxvnjcvr(thzkndmauz) = wjykzikhdx ibhronwfkf (kjeofomlcg, 1.2 - 2.3) Met View more	Positive	13 May 2024
NCT04848506 (FOREST-HCM, Corporate Publications) Manual	Phase 2	Cardiomyopathy, Hypertrophic	46	Aficamten	mqapcskhyi(ujwxswqewt) = none mtmlelgiyu (ciikehkmtr ) View more	Positive	05 Apr 2024

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