Written By: Pharmacally Medical News Desk
Cytokinetics announced that the U.S. Food and Drug Administration has approved MYQORZO™ (aficamten) for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The approval represents a major milestone for patients living with this inherited heart condition and introduces a new, mechanism-based therapy designed to improve functional capacity and reduce disease-related symptoms. The decision is supported by positive Phase 3 clinical trial data demonstrating meaningful improvements in exercise performance, symptom burden, and cardiac hemodynamics compared with placebo.
Robert I. Blum, President and Chief Executive Officer of Cytokinetics, described the approval as a defining moment for the company, marking its transition from scientific discovery to delivering an FDA-approved medicine. He highlighted that the approved label and REMS support practical clinical use, including a flexible dosing approach, a predictable safety profile, and no requirement for routine drug–drug interaction monitoring.
About MYQORZO (Aficamten)
Aficamten is a next-generation, selective cardiac myosin inhibitor developed to directly target the underlying hypercontractility that defines obstructive hypertrophic cardiomyopathy. In oHCM, excessive myosin–actin interaction leads to abnormal thickening of the heart muscle and obstruction of blood flow from the left ventricle. MYQORZO reduces excessive myosin activity, lowering left ventricular outflow tract (LVOT) obstruction and improving cardiac filling and pumping efficiency. When appropriately dosed and monitored, this targeted approach enables symptom relief without suppressing normal cardiac function.
Clinical Evidence: SEQUOIA-HCM Phase 3 Trial
The FDA approval is primarily based on results from the pivotal Phase 3 SEQUOIA-HCM trial (NCT05186818), a randomized, double-blind, placebo-controlled study in adults with symptomatic oHCM.
Topline efficacy highlights:
- Significant improvement in peak oxygen consumption (pVO₂) versus placebo, reflecting better exercise capacity
- A higher proportion of patients achieved at least one NYHA functional class improvement
- Marked reductions in resting and provoked LVOT gradients, indicating effective relief of obstruction
- Consistent benefits observed across key secondary endpoints related to symptoms and functional status
These findings demonstrate that aficamten delivers clinically meaningful improvements in both physiological measures and patient-reported functional outcomes.
Boxed Warning, Heart Failure Risk, and REMS Program Overview
MYQORZO carries a boxed warning for the risk of heart failure due to systolic dysfunction, as excessive cardiac myosin inhibition may lead to reductions in left ventricular ejection fraction (LVEF). To address this risk, treatment requires careful patient selection, baseline cardiac assessment, and ongoing monitoring of cardiac function. As part of the approval, the FDA has mandated a Risk Evaluation and Mitigation Strategy (REMS) program to ensure safe use, including echocardiographic monitoring and protocol-driven dose adjustments or treatment interruption if LVEF declines below defined thresholds.
Safety and Tolerability
Across the clinical development program, MYQORZO was generally well-tolerated when used with echocardiographic monitoring and individualized dose titration. The safety profile was consistent with its mechanism of action, with a focus on avoiding excessive reductions in cardiac contractility. Discontinuations due to adverse events were infrequent, and most reported side effects were mild to moderate in severity.
Martin Maron, MD, Director of the Hypertrophic Cardiomyopathy Center at Lahey Hospital and Medical Center and principal investigator of SEQUOIA-HCM, noted that MYQORZO represents a meaningful new option for patients with symptomatic oHCM. He emphasized that the therapy improved exercise capacity and reduced symptoms while remaining well-tolerated, positioning it as an important advancement in the clinical management of this disease.
Lisa Salberg, Founder and CEO of the Hypertrophic Cardiomyopathy Association (HCMA), highlighted the long-standing lack of effective treatment options for patients with symptomatic oHCM. She described the approval of MYQORZO as a long-awaited and hopeful development for the patient community and underscored the importance of patient-centered collaboration in bringing new therapies forward.
Next Steps and Future Development
With FDA approval secured, Cytokinetics plans to proceed with the U.S. commercial launch of MYQORZO while continuing post-marketing studies and long-term follow-up to further evaluate real-world safety and effectiveness. The company is also exploring aficamten in broader cardiomyopathy populations and additional clinical settings, reinforcing its long-term commitment to advancing targeted therapies in cardiac muscle disease.
Understanding Obstructive Hypertrophic Cardiomyopathy
Obstructive hypertrophic cardiomyopathy is a common inherited heart disorder characterized by abnormal thickening of the heart muscle that can obstruct blood flow and impair normal cardiac function. Patients often experience shortness of breath, fatigue, chest pain, dizziness, or fainting, leading to significant limitations in daily activities. Despite existing pharmacologic and procedural options, many patients continue to have persistent symptoms, highlighting the need for novel, mechanism-based treatments such as MYQORZO.
References
Cytokinetics Announces FDA Approval of MYQORZO™ (aficamten) for the Treatment of Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy to Improve Functional Capacity and Symptoms, 19 December 2025, https://ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Announces-FDA-Approval-of-MYQORZO-aficamten-for-the-Treatment-of-Adults-with-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-to-Improve-Functional-Capacity-and-Symptoms/default.aspx
Aficamten vs Placebo in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy (SEQUOIA-HCM) (SEQUOIA-HCM), ClinicalTrials.gov ID NCT05186818, https://clinicaltrials.gov/study/NCT05186818
Martin S. Maron et al, Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy, Published May 13, 2024, N Engl J Med 2024;390:1849-1861, DOI: 10.1056/NEJMoa2401424