aficamten (CK-274) / Cytokinetics, Ji Xing Pharma, Bayer - LARVOL DELTA

Hypertrophic cardiomyopathy: insights into pathophysiology and novel therapeutic strategies from clinical studies. (PubMed, Egypt Heart J) - "The review underscored the significance of early diagnosis and personalized treatment approaches in managing HCM. Future research should prioritize the development of robust biomarkers for early detection and risk stratification, particularly in diverse populations, to enhance clinical outcomes. Furthermore, it is imperative to delve deeper into the genetic mutations and molecular mechanisms associated with HCM, with a focus on exploring the roles of less-studied myocardial relaxation proteins and their interactions with sarcomere constituents."

Journal • Review • Cardiomyopathy • Cardiovascular • Gene Therapies • Hypertrophic Cardiomyopathy • TTN

Efficacy and Safety of Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials. (PubMed, Cardiol Rev) - "CMIs, including mavacamten and aficamten, significantly improve clinical outcomes in HCM patients with a manageable safety profile. These results indicate that CMIs offer a promising noninvasive alternative to septal reduction therapies."

Journal • Retrospective data • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • TNNI3

Cytokinetics Announces European Medicines Agency Validation of Marketing Authorization Application for Aficamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy (GlobeNewswire) - "Cytokinetics, Incorporated...today announced that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for aficamten, a next-in-class cardiac myosin inhibitor, for the treatment of obstructive hypertrophic cardiomyopathy (HCM). The MAA will now be reviewed by the Committee for Medicinal Products for Human Use (CHMP)...The MAA is supported by the results 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 HCM, which were published in the New England Journal of Medicine."

EMA approval • Obstructive Hypertrophic Cardiomyopathy

Cardiac Myosin Inhibitors for Obstructive Hypertrophic Cardiomyopathy: A Meta-analysis of Randomized Placebo-Controlled Trials. (PubMed, Am J Cardiovasc Drugs) - "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."

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

The clinical utility of cardiac myosin inhibitors for the management of hypertrophic cardiomyopathy: a scoping review. (PubMed, Heart Fail Rev) - "A PRISMA search strategy was carried out to identify the pertinent literature on mavacamten and aficamten-two novel CMIs. Based on the results of the studies included in this review, cardiac myosin inhibitors have been proven to be a safe and efficacious second-line option for the management of HCM. In the foreseeable future, based on results of ongoing studies investigating patient outcomes and side-effect profile, CMIs may potentially play a larger role as part of standard treatment of HCM."

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

Obstructive hypertrophic cardiomyopathy: from genetic insights to a multimodal therapeutic approach with mavacamten, aficamten, and beyond. (PubMed, Egypt Heart J) - "The introduction of cardiac myosin inhibitors heralds a new era in the management of oHCM. By directly targeting the molecular mechanisms underpinning the disease, these novel therapies offer improved symptom relief and functional outcomes. Ongoing research into the genetic basis of HCM and the development of targeted treatments holds promise for further enhancing patient care. Future studies should continue to refine these therapeutic strategies and explore their long-term benefits and potential in diverse patient populations. This review makes a significant contribution to the field by synthesizing the most recent AHA guidelines, emphasizing the crucial role of tailored management strategies in optimizing outcomes for patients with oHCM, and promoting the incorporation of cutting-edge genomics and imaging modalities to enhance personalized care."

Journal • Review • Cardiomyopathy • Cardiovascular • Fatigue • Fibrosis • Genetic Disorders • Hypertrophic Cardiomyopathy • Immunology • Obstructive Hypertrophic Cardiomyopathy • Pulmonary Disease • MYH7

Cytokinetics Announces FDA Acceptance of New Drug Application for Aficamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy (Cytokinetics Press Release) - "Cytokinetics, Incorporated...announced that the U.S. Food & Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) for aficamten, a next-in-class cardiac myosin inhibitor, for the treatment of obstructive hypertrophic cardiomyopathy...The FDA assigned the NDA a standard review with a Prescription Drug User Fee Act (PDUFA) target action date of September 26, 2025. The FDA is not currently planning to hold an advisory committee meeting to discuss the application...The results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial, which form the foundation of the NDA, demonstrated that aficamten has a positive impact on exercise capacity, clinical outcomes, symptom burden and cardiac biomarkers in patients with HCM..."

FDA filing • PDUFA • Obstructive Hypertrophic Cardiomyopathy

Great to see the ongoing and increasing activity in the cardiomyopathy space. Today it was announced that aficamten's application to the FDA for the treatment of symptomatic oHCM was accepted, with a target decision date (PDUFA) of 9/26/2025 (LinkedIn)

Open-Label Study Finds Aficamten Could Help Most oHCM Patients Avoid Surgery - "'This is an open level study, so you can't always take everything from it and say, 'I have the highest level of evidence [and] that this is being achieved'. However, what I would argue is day in, day out, in the clinic, this is what we use to treat patients,' explained Ahmad Masri, MD, MS...in an interview with HCPLive. 'We use their symptoms, their LVOT gradient, how they feel, my impression or the physician's impression of what's going on, and we recommend to them surgery or no surgery.'"

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Cardiac Myosin Inhibitors Improve Hemodynamics and Symptom Burden in Symptomatic Hypertrophic Cardiomyopathy: An Updated Meta-Analysis (AHA 2024) - "Introduction: Cardiac myosin inhibitors (CMI), including mavacamten and more recently aficamten, are emerging therapies in the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) that facilitate ventricular relaxation by reducing myosin-actin crossbridge formations. This is the largest pooled analysis assessing the efficacy of CMI in patients with HCM. Evidence from this analysis suggests that CMIs improved hemodynamic measures and symptom burden in patients with HCM."

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

Cytokinetics and Bayer Announce Exclusive Licensing Collaboration for Aficamten in Japan (GlobeNewswire) - "Cytokinetics, Incorporated...announced they have entered into a collaboration and license agreement for the exclusive development and commercialization of aficamten in Japan for the treatment of patients with obstructive and non-obstructive hypertrophic cardiomyopathy (HCM), subject to certain reserved development rights of Cytokinetics...Under the joint development plan, Bayer will conduct a Phase 3 clinical trial in Japanese patients with obstructive HCM and Cytokinetics will expand ACACIA-HCM, the ongoing Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, into Japan to support the potential marketing authorization of aficamten in Japan and CEDAR-HCM, its ongoing study for a pediatric population of patients with obstructive HCM."

Licensing / partnership • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

The Efficacy and Safety of Cardiac Myosin Inhibitors Versus Placebo in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials (AHA 2024) - "Recently, myosin inhibitors have emerged as a novel therapeutic targeting cardiac muscle hypercontractility.ObjectiveTo assess the efficacy and safety of myosin inhibitors mavacamten and aficamten in patients with oHCM.MethodsWe systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing mavacamten or aficamten to placebo in patients with symptomatic oHCM. Compared to placebo, myosin inhibitors were associated with improvement of ≥1 NYHA-FC (RR 2.33; 95%CI 1.92-2.82), rLVOT (MD -38.53; 95%CI [-46.06]-[-30.99]), vLVOT (MD -47.29; 95%CI [-58.03]-[-36.55]), pVO2 (MD 1.66; 95%CI 1.12-2.19), and KCCQ (MD 7.79; 95%CI 5.63-9.94) (Figure1). Other outcomes were similar with drug and placebo.ConclusionCardiac myosin inhibitors are an effective and safe short-term treatment for symptomatic oHCM."

Retrospective data • Cardiomyopathy • Cardiovascular • Genetic Disorders • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Cardiac Myosin inhibitors in patients with Symptomatic Hypertrophic Cardiomyopathy: An updated Systematic review and Meta-analysis of randomized trials. (AHA 2024) - "In contrast, cardiac myosin inhibitors (CMI), such as aficamten and mavacamten, represent a promising pharmacological alternative to alleviate left ventricular outflow tract obstruction. This meta-analysis highlights the potential of CMI as a promising pharmacological therapy for managing symptomatic HCM, with significant improvements in NYHA functional class, quality of life and NT-proBNP levels."

Retrospective data • Review • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

From amoeboid myosin to unique targeted medicines for a genetic cardiac disease. (PubMed, Front Physiol) - "Young investigators often ask me how I incorporated biotech opportunities into my otherwise purely academic research endeavors. Here I tell the story of the foundational basic science and early events of my career that led to forming the biotech companies responsible for the development of unique cardiac drugs, including mavacamten, a first in class human β-cardiac myosin inhibitor that is changing the lives of hypertrophic cardiomyopathy patients."

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

Changes in EQ-5D-5L with Aficamten in Obstructive Hypertrophic Cardiomyopathy (oHCM): the SEQUOIA-HCM Trial (AHA 2024) - P3 | "Aficamten yielded early, sustained and significant improvement in overall QoL compared with placebo. Withdrawal of aficamten was associated with the loss of treatment benefits and perhaps an increased perception of pre-treatment symptoms. These data support a role of aficamten in improving QoL among patients with oHCM."

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

Aficamten Versus Placebo in Patients With Hypertrophic Obstructive Cardiomyopathy: A Systematic Review and Meta-Analysis. (PubMed, Am J Ther) - No abstract available

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

Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials (AHA 2024) - "A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM... Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed."

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

Modifiability of Post-Exercise Oxygen Uptake Recovery Patterns: A Substudy of the SEQUOIA-HCM Randomized Trial (AHA 2024) - "Shortening of t12.5% correlated with reduced NT-proBNP, high-sensitivity cardiac troponin I, left ventricular outflow tract gradient, and improved NYHA FC and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (all p<0.005).ConclusionThis is the first study to establish that VO2Rec is modifiable in response to cardio-specific intervention (aficamten) in patients with oHCM. VO2Rec (t12.5%) shortened proportionally and in parallel with other metrics of improved cardiac function, underscoring the benefits of aficamten for oHCM, and supporting inclusion of VO2Rec as a routine metric for evaluating cardio-specific interventions for oHCM."

Clinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • TNNI3

Efficacy and Safety of Aficamten in Patients Guideline-Eligible for Septal Reduction Therapy in the FOREST-HCM Trial (AHA 2024) - P2/3 | "A third of pts enrolled in FOREST-HCM were guideline SRT-eligible at baseline despite optimized standard of care therapy, with almost all pts no longer meeting SRT-eligibility criteria by 24 weeks with aficamten treatment. Aficamten may provide an effective alternative to SRT in some patients with oHCM."

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

Cardiac Myosin Inhibition in Obstructive Hypertrophic Cardiomyopathy: Can Aficamten Stand Alone? (PubMed, J Am Coll Cardiol) - No abstract available

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

Standard-of-Care Medication Withdrawal in Patients With Obstructive Hypertrophic Cardiomyopathy Receiving Aficamten in FOREST-HCM. (PubMed, J Am Coll Cardiol) - P2/3 | "In FOREST-HCM, one-half of the patients with oHCM attempted downtitration and withdrawal of SoC medications while receiving aficamten treatment, with infrequent instances of resumption of SoC. Stopping and dose reduction of SoC medications were well tolerated with no adverse consequences in clinical measures of efficacy (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in Hypertrophic Cardiomyopathy [FOREST-HCM]; NCT04848506)."

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

Now published in JACC Journals - results from the withdrawal of SoC meds in FOREST-HCM (BB/CCB/disopyramide) while on #aficamten https://lnkd.in/ggVRJ8Q6 Previously presented at ESC2024 https://lnkd.in/gy7xw3BV (LinkedIn)

Global remodeling on aficamten vs placebo - an analysis from #SEQUOIA #HCM presented at the Hypertrophic Cardiomyopathy Medical Society (HCMS) Scientific Sessions (LinkedIn)

Cardiology Month in Review: September 2024 - "Key Opinion Leader Perspectives: Ahmad Masri, MD, MS, on Aficamten in HCM."

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Aficamten in Hypertrophic Cardiomyopathy: Roots and Branches of SEQUOIA. (PubMed, J Am Coll Cardiol) - No abstract available

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy