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

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

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

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

MAPLE-HCM: Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM (clinicaltrials.gov) - P3 | N=175 | Completed | Sponsor: Cytokinetics | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Mar 2025 | Trial primary completion date: Jul 2025 ➔ Feb 2025

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

Cytokinetics Announces New PDUFA Date for Aficamten in Obstructive Hypertrophic Cardiomyopathy (Cytokinetics Press Release) - "Cytokinetics, Incorporated...announced that the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) action date for the New Drug Application (NDA) for aficamten for the treatment of patients with obstructive hypertrophic cardiomyopathy (oHCM) to December 26, 2025. The FDA recently notified Cytokinetics that additional time is required to conduct a full review of the company’s proposed Risk Evaluation and Mitigation Strategy (REMS)."

PDUFA • Obstructive Hypertrophic Cardiomyopathy

Can Generative AI Conduct Evidence Gap Analysis in HEOR? A Case Study of Hypertrophic Cardiomyopathy Using ValueGen.AI [WITHDRAWN] (ISPOR 2025) - "Generative AI can rapidly and effectively identify literature gaps, as demonstrated by ValueGen.AI in revealing deficiencies in epidemiological data across diverse populations and limited real-world evidence on patient-reported outcomes and costs in HCM."

Case study • Clinical • HEOR • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy

Concomitant Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy. (PubMed, JACC Heart Fail) - P2, P2/3, P3 | "In this cohort of patients with symptomatic oHCM with persistent LVOT obstruction, combination therapy with aficamten and disopyramide was safe and well tolerated but did not enhance clinical efficacy vs aficamten alone. For such oHCM patients, aficamten treatment may be considered with an option to discontinue disopyramide. (Dose-finding Study to Evaluate the Safety, Tolerability, PK, and PD of CK-3773274 in Adults With HCM [REDWOOD-HCM]; NCT04219826) (Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [SEQUOIA-HCM]; NCT05186818) (Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM [FOREST-HCM]; NCT04848506)."

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

Cardiac myosin inhibition in hypertrophic cardiomyopathy: review of the evolving evidence base. (PubMed, Expert Rev Cardiovasc Ther) - "Mavacamten and aficamten are the first 2 drugs in this class with high-quality phase III randomized clinical trial data (Based on PUBMED search, last query April 2025). There is a growing body of evidence based on high-quality scientific investigation that are broadening the therapeutic options for patients with this condition. However, as different drugs emerge in the same class, it is crucial to appreciate clinically meaningful class-based effects vs. specific drug differences."

Clinical • Journal • Review • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Efficacy of aficamten in obstructive hypertrophic cardiomyopathy: A systematic review and meta-analysis. (PubMed, Am Heart J Plus) - "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."

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

Clinical Evaluation of the Effect of Aficamten on QT/QTc Interval in Healthy Participants. (PubMed, Clin Transl Sci) - P3 | "Part A (n = 10) was an open-label study to find the appropriate dose for thorough QT (TQT) evaluation in Part B. Part B (n = 34) was a double-blind, 3-way crossover TQT study conducted as per ICH E14 guidance using negative (placebo) and positive (moxifloxacin) controls. Aficamten was generally well tolerated. In conclusion, there was no evidence of aficamten-mediated QTc prolongation across the therapeutic concentration range in a formal TQT study."

Clinical • Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

SAFETY AND OUTCOMES OF CONCOMITANT AFICAMTEN AND DISOPYRAMIDE USE AND WITHDRAWAL IN PATIENTS WITH OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY: AN ANALYSIS OF REDWOOD-HCM COHORT 3, SEQUOIA-HCM, AND FOREST-HCM TRIALS - Ahmad Masri (ACC 2025) - "The addition of aficamten to diso for a selected group of oHCM patients with persistent LVOT obstruction was safe and effective. Furthermore, withdrawal of diso did not compromise efficacy of aficamten."

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

ATRIAL AND VENTRICULAR ARRHYTHMIAS IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY TREATED WITH CARDIAC MYOSIN INHIBITORS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS - Luis Rene Puglla Sanchez (ACC 2025) - "In this meta-analysis of RCTs among patients with HCM, there was no difference in the incidence of supraventricular or ventricular arrhythmias in patients treated with CMI or placebo over a mean follow-up of 23 weeks."

Retrospective data • Review • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

EFFECT OF AFICAMTEN TREATMENT FOR UP TO 72 WEEKS ON CARDIAC STRUCTURE AND FUNCTION IN PATIENTS WITH OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY: THE SEQUOIA-HCM AND FOREST-HCM CMR SUB-STUDIES - Ahmad Masri (ACC 2025) - "Longer-term treatment with aficamten over 48-72 weeks resulted in favorable cardiac remodeling with reduction in LV mass, LA volume, and MR while myocardial fibrosis remained stable."

Clinical • Cardiomyopathy • Cardiovascular • Fibrosis • Hypertrophic Cardiomyopathy • Immunology • Obstructive Hypertrophic Cardiomyopathy

EVALUATION OF CYTOCHROME P450 2C9, 2C19, AND 2D6 INHIBITION ON THE PHARMACOKINETICS OF AFICAMTEN IN HEALTHY PARTICIPANTS - Neha Maharao (ACC 2025) - "AFI was given alone and with multiple daily doses (≥9 days before AFI dosing) of fluconazole (FLZ; strong CYP2C19 and moderate CYP 2C9/3A inhibitor), paroxetine (PRX; strong selective CYP2D6 inhibitor), and fluoxetine (FLX; strong CYP 2C19/2D6 inhibitor). AFI was primarily eliminated by CYP2C9 (fraction metabolized [fm]=50%), with contributions from CYPs 3A (fm=26%, historical data), 2D6 (fm=21%), and 2C19 (fm=3%). Weak DDIs are likely from strong inhibition of any one pathway and only moderate DDIs are expected with moderate to strong multi-pathway inhibitors."

Clinical • PK/PD data • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • CYP2C19 • CYP2C9

CARDIAC MYOSIN INHIBITORS FOR HYPERTROPHIC CARDIOMYOPATHY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS - Adeel Ahmad (ACC 2025) - "CMIs can contribute to improving key efficacy outcomes for patients withhypertrophic cardiomyopathy while reducing the incidence of SRT."

Retrospective data • Review • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

UNDERSTANDING THE IMPACT OF PLACEBO ON PATIENT-REPORTED HEALTH STATUS: AN ANALYSIS FROM SEQUOIA-HCM - Charles Sherrod (ACC 2025) - P3 | "Background: Given that patient-reported outcomes are often considered particularly susceptible to placebo effects and their growing importance in obstructive hypertrophic cardiomyopathy (oHCM), clinicians need to understand how much changes in placebo-assigned patients' health status may be due to a 'placebo effect' rather than more intensive care at specialized oHCM centers, changes in treatment adherence, or regression to the mean. In the SEQUOIA-HCM study (NCT05186818), patients with symptomatic oHCM were randomized to aficamten or placebo and treated for 24 weeks, followed by blinded treatment withdrawal... In SEQUOIA-HCM, about one-third of the KCCQ-OSS improvement in those treated with placebo was due to placebo effects, and the residual improvement was due to other unmeasured effects. These findings suggest that changes in health status following placebo treatment should not be completely ascribed to placebo effects."

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

A Characterization of the Nonclinical Pharmacology and Toxicology of Aficamten, a Reversible Allosteric Inhibitor of Cardiac Myosin. (PubMed, Int J Toxicol) - "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."

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