What is Camzyos (mavacamten)?

Mavacamten (Camzyos): A First-in-Class Cardiac Myosin Inhibitor for Obstructive Hypertrophic Cardiomyopathy

Mavacamten (Camzyos) is a first-in-class cardiac myosin inhibitor FDA-approved for treating symptomatic obstructive hypertrophic cardiomyopathy (HCM) in adults, which works by reducing excessive cardiac contractility to improve left ventricular outflow tract obstruction (LVOTO), symptoms, and functional capacity. 1

Mechanism of Action and Clinical Use

Mavacamten works by:

• Inhibiting cardiac myosin, reducing actin-myosin interaction
• Decreasing myocardial contractility
• Reducing left ventricular outflow tract obstruction
• Improving diastolic function (relaxation)

It is indicated for:

• Adult patients with symptomatic obstructive HCM (NYHA class II-III)
• Patients who remain symptomatic despite first-line therapies (beta-blockers or non-dihydropyridine calcium channel blockers) 1

Efficacy

Clinical trials have demonstrated that mavacamten:

• Reduces LVOT gradients by 25-89.5 mmHg (depending on dosing and concomitant medications) 2
• Improves exercise capacity with increased peak oxygen consumption (1.7-3.5 mL/kg/min) 2
• Enhances patient-reported outcomes and quality of life 3
• Reduces eligibility for invasive septal reduction therapy in patients with drug-refractory symptoms 3
• Shows evidence of favorable cardiac remodeling on imaging studies 3

Place in Therapy

According to the 2024 AHA/ACC guidelines:

1. First-line therapy: Non-vasodilating beta-blockers
2. Alternative first-line: Verapamil or diltiazem (calcium channel blockers)
3. Advanced therapies (for those who don't respond to first-line):
   • Mavacamten (adult patients only)
   • Disopyramide (with AV nodal blocking agent)
   • Septal reduction therapy (SRT) 1

Dosing and Monitoring

• Starting dose varies from 2-5 mg/day (with beta-blockers) to 10-20 mg/day (without background medications) 2
• Dose titration is guided by echocardiographic monitoring of:
  • LVOT gradient (Valsalva)
  • Left ventricular ejection fraction (LVEF) 4
• Requires REMS (Risk Evaluation and Mitigation Strategy) program enrollment due to risk of heart failure 5
• Regular echocardiograms are mandatory before initiation and during treatment 5

Safety Considerations

Important risks:

• Heart failure due to decreased LVEF (observed in 5.7-10% of patients) 1
• LVEF must be monitored regularly; mavacamten should be interrupted or discontinued if LVEF <50% 1
• Contraindicated during pregnancy due to potential teratogenic effects 1, 5
• Drug interactions with CYP2C19 inhibitors/substrates require dose adjustments 5, 4

Common adverse effects:

• Dizziness
• Syncope (fainting)
• Decreased LVEF at higher plasma concentrations
• Atrial fibrillation 5, 2

Special Considerations

• Contraindicated during pregnancy; effective contraception required during treatment and for 4 months after the last dose 5
• Must be discontinued if LVEF <50% persists 1
• Avoid pure vasodilators (dihydropyridine calcium channel blockers, ACE inhibitors, ARBs) in patients with obstructive HCM as they may worsen outflow tract obstruction 1, 6
• Careful monitoring needed during intercurrent illness which may affect systolic function 4

Mavacamten represents a significant advancement in the management of obstructive HCM, offering a targeted approach to address the underlying pathophysiology of the disease beyond symptom management alone.