Camzyos (mavacamten) / BMS - LARVOL DELTA

Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Targeting Sarcomeric Hypercontractility with Demonstrated Long-Term Safety and Efficacy-A Narrative Review. (PubMed, J Clin Med) - "Landmark trials, including EXPLORER-HCM and MAVERICK-HCM, underscore mavacamten's ability to reduce LVOT gradients, enhance diastolic function, and lower cardiac biomarkers, heralding a paradigm shift from symptomatic management to disease-modifying therapy. Despite current knowledge gaps in long-term outcomes and diverse population responses, mavacamten establishes a critical foundation for molecularly targeted therapeutics in HCM and broader cardiomyopathies."

Journal • Review • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • CYP2C19

Mavacamten in the Treatment of Obstructive Hypertrophic Cardiomyopathy: from Pathophysiology To Real World Data. (PubMed, Curr Cardiol Rep) - "Its integration into routine care is expanding, supported by real-world evidence. Ongoing studies will clarify its role in non-obstructive HCM, heart failure with preserved ejection fraction, pediatric populations, and early-stage disease."

Journal • Real-world evidence • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pediatrics

MAVEN: Real-World Effectiveness of Mavacamten in Canada (clinicaltrials.gov) - P=N/A | N=115 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Real-world evidence • Trial completion • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Therapeutic Response to Myosin Inhibitor Therapy in Noonan Syndrome-Associated Obstructive Hypertrophic Cardiomyopathy. (PubMed, JACC Case Rep) - "Myosin inhibitors may benefit syndromic HOCM. Further research is warranted."

Journal • Cardiomyopathy • Cardiovascular • Genetic Disorders • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pulmonary Disease

Phenotype specific nuclear lamina remodeling in hiPSC derived cardiomyocytes bearing TNNT2 sarcomeric variants. (PubMed, iScience) - "These changes in stiffness were rescued by treatment with myosin modulators Mavacamten or Omecamtiv Mecarbil. This study shows that nuclear mechanics is influenced by the interaction between the sarcomere and the cytoskeletal network. Exploring the relationship between contractile dysfunction and nuclear lamina remodeling may reveal new therapeutic targets for cardiomyopathies."

Journal • Cardiomyopathy • LMNA

Mavacamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy During Active Chemotherapy. (PubMed, JACC Case Rep) - "Mavacamten can substantially improve quality of life in oHCM, even in patients with active malignancy."

Journal • Cardiomyopathy • Cardiovascular • Colon Cancer • Colorectal Cancer • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Oncology • Palliative care • Pulmonary Disease • Solid Tumor

CYP450 activity, drug interactions and genetic polymorphisms: clinical relevance for the new selective cardiac myosin inhibitors. (PubMed, Expert Opin Drug Saf) - "Two new cardiac myosin inhibitors (CMIs), mavacamten and aficamten, reduce the intensity of myosin - actin cross-bridge formation and could treat causes of HCM. However, CYP3A4 can influence the disposition of these CMIs and other drugs, as CYP3A4 is subjected to induction and inhibition, and modulation by inflammatory factors. Therefore, multi-drug interactions due to changes in the metabolic clearances of CMIs are expected in HCM patients with other chronic conditions and polypharmacy."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • CYP2C19 • CYP2C9 • CYP3A4

Long-Term Real-World Outcomes of Mavacamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy up to 108 Weeks. (PubMed, J Clin Med) - "Doses of background beta blocker and nondihydropyridine calcium channel blocker were significantly reduced during the study period (p < 0.001). In this large single-center real-world experience of mavacamten therapy, mavacamten was highly effective and maintained an acceptable safety profile, comparable to the clinical trial long-term extension experience."

Journal • Real-world evidence • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Catastrophic apical ballooning in an obstructive hypertrophic cardiomyopathy patient treated with mavacamten: case report. (PubMed, Eur Heart J Case Rep) - "Recently, myosin inhibitors (mavacamten, aficamten) have been introduced to specifically counteract LVOTO. To the best of our knowledge, this is the first report describing apical ballooning in oHCM during mavacamten treatment. The causal role of mavacamten in this acute heart failure case is unproven, yet-being a cardiac myosin inhibitor and considering the shock recurrence after initial recovery-plausible."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pulmonary Disease

Cryo-EM Reveals How Cardiomyopathy Therapeutic Drugs Modulate the Myosin Motors of the Heart. (PubMed, bioRxiv) - "Mavacamten and omecamtiv mecarbil are therapeutic, myosin-targeted drugs designed to treat these myopathies, but their mechanism of action has remained unclear. This remodeling elucidates previously unclear allosteric mechanisms through which these drugs either inhibit or enhance myosin activity, countering the deleterious impacts of disease. These findings reveal how drugs modulate myosin structure to control cardiac contractility."

Journal • Cardiomyopathy • Cardiovascular • Myositis

Emerging Pharmacological and Invasive Therapies for Hypertrophic Cardiomyopathy with Obstructive Physiology. (PubMed, Card Fail Rev) - "Emerging pharmacological approaches, including EDG-7500 and gene therapies, aim to refine treatment strategies...Innovations such as radiofrequency ablation and septal scoring along the midline endocardium (SESAME) offer promising, minimally invasive alternatives. As treatment options expand, optimising patient selection, monitoring protocols and long-term outcomes remain essential to advancing care for patients with obstructive hypertrophic cardiomyopathy."

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

Model-Based Economic Evaluation of the First-in-Class Myosin Inhibitor Mavacamten Versus Care as Usual in Obstructive Hypertrophic Cardiomyopathy Patients from a Dutch Societal Perspective. (PubMed, Pharmacoeconomics) - "Conclusion The results show that mavacamten increased LYs and QALYs compared with SoC, however, at substantial additional costs. The probability of mavacamten being cost effective depends on the selected willingness-to-pay threshold."

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

Net health benefit of mavacamten for the treatment of Chinese patients with obstructive hypertrophic cardiomyopathy: a model-based economic evaluation. (PubMed, Front Pharmacol) - P3 | "Over a lifetime horizon, mavacamten ± BB/CCBs demonstrated superior health outcomes versus BB/CCB monotherapy, with incremental gains in life-years (15.76 vs. 14.40) and quality-adjusted life-years (QALYs: 13.69 vs. 11.38). Mavacamten provides substantial health benefits for Chinese obstructive HCM patients, including clinically meaningful improvements in survival and quality-of-life metrics relative to standard care."

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

CT.APB.05: Beyond Ejection Fraction: Innovations and Inequities in Heart Failure and Cardiomyopathy Care (AHA 2025) - "Gain insight into the safety profile of mavacamten, the lived burden of transthyretin amyloid cardiomyopathy, and strategies to improve adherence and symptom recognition in everyday care...This is not a CE accredited session. Poster Professor(s): Matthew MartinezPamela Peterson (DENVER HEALTH MEDICAL CENTER)"

Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation • Rare Diseases

A 'non-muscle' alpha-actinin is an intrinsic component of the cardiac Z-disc and regulates sarcomere turnover, contractility, and heart remodeling (AHA 2025) - "The addition of Mavacamten to ACTN4-depletion media was sufficient to restore the wild-type iPSC-CM phenotype... Our findings suggest a "non-muscle" actinin regulates heart contractility and influences clinical outcomes related to heart failure in humans."

Cardiovascular • Congestive Heart Failure • Heart Failure • ACTN4

ODYSSEY_HCM: A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy (clinicaltrials.gov) - P3 | N=580 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | Trial completion date: Jun 2029 ➔ Oct 2025

Trial completion • Trial completion date • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy

Effect of Mavacamten and Disopyramide on Left Ventricular Mechanical Dispersion and Life-threatening Arrhythmia in Obstructive Hypertrophic Cardiomyopathy. (PubMed, Eur Heart J Cardiovasc Imaging) - "Mavacamten, but not disopyramide decreased LVMD, GWW and increased GWE in obstructive HCM. LVMD <72 ms at follow-up is promising for assessing the risk for life-threatening ventricular arrhythmias."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Ventricular Tachycardia

Myosin Inhibitors for the Treatment of Obstructive Hypertrophic Cardiomyopathy: A Canadian Perspective on a First-in-Class Therapy. (PubMed, Can J Physiol Pharmacol) - "As such, many general cardiologists, internists, and family physicians will need to be familiar with these agents. This review on the myosin inhibitors, particularly mavacamten, provides a perspective for more general cardiovascular providers by summarizing the key mechanisms, clinical trials, expected outcomes, and potential impacts on the Canadian healthcare system."

Journal • Cardiomyopathy • Cardiovascular • Fatigue • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pain • Pulmonary Disease

ALPK3 Cardiomyopathy: Integrative Review With Systematic Variant Curation, Mechanisms, and Translation. (PubMed, Circ Genom Precis Med) - "Therapeutic proof‑of‑concept has now been achieved on 2 fronts: (1) pharmacological correction of sarcomeric hypercontractility with the myosin inhibitor mavacamten and (2) durable phenotypic rescue in global knockout mice using an adeno-associated virus-delivered miniALPK3 gene‑replacement construct. Together, these data position ALPK3 cardiomyopathy as a compelling target for precision medicine. Early genetic diagnosis, genotype-tailored surveillance, and focused development of gene-replacement or editing strategies, potentially combined with modulators of the ALPK3-MuRF proteostatic axis, offer a realistic path to disease-modifying therapy for this once enigmatic condition."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Gene Therapies • Heart Failure • Hypertrophic Cardiomyopathy • Immunology • Targeted Protein Degradation • SQSTM1

Transcriptional and functional effects of mavacamten in multiple porcine and human models with hypertrophic cardiomyopathy. (PubMed, Br J Pharmacol) - "These data suggest that MAVA not only inhibits force within the sarcomere but also influences transcriptional pathways in model-specific manner."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • MYBPH

Innovation in Off-Patent Competitive Environment: Key Learnings From Successes and Failures (ISPOR-EU 2025) - "Products were evaluated based on payer-perceived value, with higher ratings classified as ASMR III or "considerable added benefit" (or better), and lower ratings as ASMR V/VI or "no added benefit." Only a few products (e.g., Camzyos and Xenpozyme) achieved positive P&MA outcomes in off-patent spaces, largely due to high unmet need and meaningful improvements in clinical or quality-of-life outcomes. Success in off-patent environments remains rare and hinges on clear differentiation, high unmet need, and robust clinical evidence. Payers expect incremental benefit demonstrated through well-designed trials, with quality-of-life and secondary endpoints viewed as supportive but not sufficient. Trial design limitations remain a major barrier to positive HTA and pricing outcomes."

Mavacamten Monotherapy in Real-World Patients with Obstructive Hypertrophic Cardiomyopathy: Evidence From COLLIGO-HCM. (PubMed, Circ Genom Precis Med) - "Two patients in the mavacamten monotherapy subgroup and one patient in the mavacamten with background therapy subgroup permanently discontinued treatment owing to LVEF <50%. Mavacamten monotherapy was associated with improvements in cardiac function and symptoms, and positive benefits to the risk profile over a 9-month follow-up period; this was consistent with improvements observed in patients treated with mavacamten with background therapy."

Journal • Monotherapy • Real-world evidence • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Effect of selected baseline characteristics and exposure on efficacy and safety of mavacamten: A Post-Hoc Analysis from the ODYSSEY trial (AHA 2025) - P3 | "The ODYSSEY-HCM study was the largest randomized trial ever conducted in nHCM patients. We will report on the detailed post-hoc analysis of response to mavacamten, based on pharmacokinetic distribution and disease severity."

Clinical • Retrospective data • Cardiomyopathy • Cardiovascular • CNS Disorders • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • NPPB

Effect of Mavacamten on Measures of Cardiopulmonary Exercise Testing: An Analysis of the ODYSSEY-HCM Randomized Trial (AHA 2025) - P3 | "The ODYSSEY-HCM study was the largest randomized trial ever conducted in patients with nHCM. We will report the detailed results of analyses of CPET to better understand the disease at baseline, along with potential mechanistic insights into the impact of mavacamten on exercise performance in patients with nHCM."

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Myosin inhibition partially rescues the myofibre proteome in X-linked myotubular myopathy. (PubMed, JCI Insight) - "Hence, we treated these, with a myosin ATPase inhibitor, mavacamten. After a four-week treatment period, we observed a partial restoration of the myofibre proteome, especially proteins involved in cytoskeletal, sarcomeric and energetic pathways. Altogether, our study highlights myosin inhibition as a new potential drug mechanism for the complex XLMTM muscle phenotype."

Journal • CNS Disorders • Myositis