aficamten (CK-274) / Cytokinetics, CORXEL, Bayer - LARVOL DELTA

REDWOOD-HCM, SEQUOIA-HCM and FOREST-HCM trials: Incidence and impact of atrial fibrillation in oHCM with aficamten (ESC-WCC 2025) - No abstract available

Late-breaking abstract • Atrial Fibrillation • Cardiovascular • Obstructive Hypertrophic Cardiomyopathy

MAPLE-HCM: aficamten vs metoprolol in oHCM (ESC-WCC 2025) - No abstract available

Cardiovascular • Obstructive Hypertrophic Cardiomyopathy

Efficacy and safety of long-term treatment with aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy: results from FOREST-HCM (ESC-WCC 2025) - No abstract available

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Aficamten in patients with obstructive hypertrophic cardiomyopathy: an integrated safety analysis (ESC-WCC 2025) - No abstract available

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Effect of Aficamten Compared with Metoprolol on Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy: A pre-specified analysis of MAPLE-HCM (ESC-WCC 2025) - No abstract available

Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Cardiac myosin inhibitors in hypertrophic cardiomyopathy. (PubMed, J Cardiovasc Imaging) - "Mavacamten, the first selective and reversible cardiac myosin inhibitor (CMI), has been introduced to the clinical arena for the treatment of obstructive hypertrophic cardiomyopathy (HCM)...Aficamten, a next-generation CMI with a shorter half-life, has also demonstrated comparable efficacy...However, future studies must provide data on hard clinical outcomes, such as heart failure hospitalization or death. Ongoing trials comparing CMI to traditional first-line therapies, such as β-blockers, will clarify their potential role as an initial therapeutic option."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

CAMELLIA-HCM: A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy (clinicaltrials.gov) - P3 | N=34 | Recruiting | Sponsor: Bayer | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy and Phenocopies: New Therapies for Old Diseases-Current Evidence and Future Perspectives. (PubMed, J Clin Med) - "In particular, many chemotherapy agents (alkylating agents, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies targeting clonal cells) allowing one to treat AL amyloidosis, transthyretin stabilizers (tafamidis and acoramidis), and gene silencers (patisiran and vutrisiran) are available in transthyretin cardiac amyloidosis, and enzyme replacement therapies (agalsidase-alpha, agalsidase-beta, and pegunigalsidase-alpha) or oral chaperone therapy (migalastat) can be used in Anderson-Fabry disease. In addition, the introduction of cardiac myosin inhibitors (mavacamten and aficamten) has deeply modified the treatment of hypertrophic obstructive cardiomyopathy. The aim of this review is to describe the new disease-modifying treatments available in HCM and phenocopies in light of current scientific evidence."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Fabry Disease • Gene Therapies • Genetic Disorders • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Rare Diseases

Aficamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: 48-Week Results From FOREST-HCM. (PubMed, JACC Heart Fail) - P2, P2/3, P3 | "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)."

Journal • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Aficamten in the treatment of obstructive hypertrophic cardiomyopathy. (PubMed, Future Cardiol) - "Aficamten was developed to optimize pharmacokinetic properties and clinical tolerability relative to its predecessor, mavacamten. Collectively, the available data suggests that aficamten is a well-tolerated drug that shows strong clinical efficacy across a wide array of clinical parameters. In this review, we provide a comprehensive description of the pharmacology, clinical efficacy, and tolerability of aficamten."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

CAMELLIA-HCM: A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy (clinicaltrials.gov) - P3 | N=34 | Not yet recruiting | Sponsor: Bayer

New P3 trial • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Cardiac myosin inhibitors for hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Ann Med Surg (Lond)) - "Subgrouping by intervention type (mavacamten vs. aficamten) revealed non-significant results for all primary outcomes. CMIs can contribute to improving key efficacy outcomes for patients with HCM while reducing incidence of SRT."

Journal • Retrospective data • Review • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Unveiling the complexity of nonobstructive hypertrophic cardiomyopathy. (PubMed, Heart Fail Rev) - "Emerging therapies, such as myosin inhibitors mavacamten and aficamten, target sarcomeric hypercontractility and show promise in early trials, but their clinical impact on nHCM is still under investigation. Gene therapies also hold potential, though their applicability to nHCM is limited by the high rate of mutation-negative cases and the potential irreversibility of advanced disease states. This review critically analyzes the pathophysiological mechanisms of nHCM, evaluates current and emerging therapeutic strategies, and provides guidance on contemporary management approaches for this complex and often underrecognized condition."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fatigue • Gene Therapies • Heart Failure • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pulmonary Disease

Cardiac myosin inhibitors: Efficacy, safety and future directions of aficamten in hypertrophic obstructive cardiomyopathy. (PubMed, Egypt Heart J) - "Aficamten is a new second-generation cardiac myosin inhibitor (CMI) that has shown promising results from clinical trials. With reports of reduced LVOT obstruction and improvement in heart failure symptoms, these findings indicate potential improvement in the quality of life of patients with HOCM."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Myosin modulator Aficamten inhibits force in cardiac muscle by altering myosin's biochemical activity without changing thick filament structure. (PubMed, bioRxiv) - "Inhibiting contractility by targeting cardiac myosin is an effective treatment for patients with hypertrophic cardiomyopathy (HCM). This is different from Mavacamten that strongly affects both. While both compounds inhibit contractility, differences in mechanisms of action and kinetics of force activation and relaxation could allow use in different patient populations."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

Cas13-Mediated RNA Base Editing Using mxABE Restores Heart Function in a Humanized Hypertrophic Cardiomyopathy Model (ASGCT 2025) - "Current treatments, such as Aficamten and Mavacamten, do not address the underlying genetic cause and have significant side effects. This study demonstrates the successful application of mxABE, a CRISPR-Cas13-based RNA base editor being developed for HCM treatment by correcting the MYH7 mutation. The AAV-mxABE therapy effectively prevented heart remodeling and restored heart function in a humanized Myh6hR403Q/+ mouse model, highlighting its potential as a safe and targeted therapeutic strategy for hereditary cardiomyopathies. Disease Focus of Abstract:Other Other: Genetic Heart Disease"

Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertrophic Cardiomyopathy • Immunology • MYH7

Integrative Approaches in the Management of Hypertrophic Cardiomyopathy: A Comprehensive Review of Current Therapeutic Modalities. (PubMed, Biomedicines) - "Beta-blockers, including atenolol and nadolol, are considered the first-line treatment due to their ability to reduce heart rate and myocardial contractility and enhance diastolic filling. Non-dihydropyridine calcium channel blockers, such as verapamil and diltiazem, are utilized as second-line agents when beta-blockers are ineffective or contraindicated...Recent advancements in cardiac myosin modulators, such as Mavacamten and Aficamten, offer targeted therapies by modulating myosin-actin interactions to reduce LVOT gradients and improve symptoms, with promising results from clinical trials...Ultimately, the treatment and prevention of atrial fibrillation and sudden cardiac death are two key points of HCM management in both obstructive and non-obstructive forms. This review aims to provide an overview of current pharmacological and invasive strategies, as well as emerging therapies, in the management of HCM."

Journal • Review • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Gene Therapies • Hypertrophic Cardiomyopathy

A plain language summary of the SEQUOIA-HCM study: aficamten for symptomatic obstructive hypertrophic cardiomyopathy. (PubMed, Future Cardiol) - No abstract available

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

SEQUOIA­HCM: Effect of aficamten treatment on patients with hypertrophic obstructive cardiomyopathy by geographical region (HEART FAILURE 2025) - No abstract available

Clinical • Late-breaking abstract • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

A de novo systematic literature review to identify the clinical effectiveness and safety of different treatments for patients with non-obstructive hypertrophic cardiomyopathy (HEART FAILURE 2025) - "A change in New York Heart Association (NYHA) class was reported in seven studies, all of which reported on 40 patients or fewer; within these the proportion of patients with ≥1 class improvement ranged from 14.7% (5/29) (ninerafaxstat arm of IMPROVE-HCM) to 79.4% (27/34) (aficamten arm of FOREST-HCM). There is a scarcity of rigorous studies reporting on non-obstructive HCM treatment and there is no significant evidence to support improved outcomes for traditional treatments, such as beta-blockers. Newer therapies which include cardiac myosin inhibitors (designed to address the underlying pathophysiology of HCM), are emerging as promising options with phase II studies demonstrating step changes in safety and efficacy, including NYHA functional class changes. Further research is needed to strengthen these findings, as current data remains limited."

Clinical • Review • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy

Efficacy and safety of aficamten in patients with obstructive hypertrophic cardiomyopathy and mild symptoms (HEART FAILURE 2025) - No abstract available

Clinical • Late-breaking abstract • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Efficacy of Aficamten in Patients with Obstructive Hypertrophic Cardiomyopathy and Mild Symptoms: Results from the SEQUIOA-HCM Trial. (PubMed, Eur Heart J) - P3 | "Patients with oHCM and mild symptoms treated with aficamten achieved significant improvement across a range of clinically relevant outcomes, and generally similar to patients with more advanced symptoms. Less severely symptomatic patients could be considered for aficamten treatment."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Efficacy of Pharmacological Therapies in Reducing Outflow Tract Obstruction in Patients with Obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis. (PubMed, Eur Heart J Cardiovasc Pharmacother) - "Pharmacological therapies effectively reduced LVOT gradients in oHCM patients to varying degrees, with disopyramide and CMIs showing the highest effect, followed by BBs and CCBs."

Journal • Retrospective data • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Cytokinetics Announces Positive Topline Results From MAPLE-HCM (GlobeNewswire) - P3 | N=175 | MAPLE-HCM (NCT05767346) | Sponsor: Cytokinetics | "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."

P3 data: top line • Obstructive Hypertrophic Cardiomyopathy

CEDAR-HCM: A Study to Evaluate the Effect of Aficamten in Pediatric Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM). (clinicaltrials.gov) - P2/3 | N=40 | Recruiting | Sponsor: Cytokinetics | Trial completion date: Dec 2028 ➔ Jan 2030 | Trial primary completion date: Dec 2028 ➔ Jan 2030

Trial completion date • Trial primary completion date • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pediatrics