Mavacamten

Trade name: Camzyos

Manufacturer: Bristol Myers-Squibb

Cost: £1073/28 days (+ Undisclosed NHS discount)

Dose = 5-15mg/d PO

Bioavailability = 85%

Metabolism = Liver (CYP2C19, CYP3A4, CYP2C9)

Terminal half life = 6-9 days (dependent on CYP2C19 activity)

Excretion = urine

Mechanism of Action

• Direct cardiac myosin inhibitor
• Decreased ATP activity
• Selectively and reversibly inhibits the action of myosin

Criteria for administration

1. HCM with LVOT obstruction
2. LVEF >55%
3. Age > 18 years
4. NYHA II-III

Exclusion criteria

1. Concurrent disopyramide, ranolazine or verapamil administration (additive risk of negative inotropy)
2. Pregnancy and breastfeeding
3. Worsening LVEF < 50% on surveillance echo post-administration

Trials

1. EXPLORER-HCM

Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial

Treatment with mavacamten improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with obstructive hypertrophic cardiomyopathy. The results of this pivotal trial highlight the benefits of disease-specific treatment for this condition.

www.thelancet.com

• Phase 3 randomised control trial published in the Lancet 2020
• 259 adults randomised to mavacamten vs placebo
• On average LVOT gradient was reduced by 36mmHg and VO2 increased by 1.6ml/kg/min on CPET testing

2. SEQUOIA-HCM

Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy | NEJM

One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from lef...

www.nejm.org

• Analysed aficamten (an alternative cardiac myosin inhibitor)
• Published in NEJM 2025
• Randomised control trial comparing 282 patients (142 Aficamten vs 140 placebo)
• 1.8ml/kg/min improvement in VO2 at 24 weeks
• Significant reduction in LVOT gradient as described in the graph below (range -44mHg —> - 57mmHg)
• A small reduction in LVEF% was seen (-4.5%) but no increase in heart failure admissions demonstrated.

Reference: https://www.nejm.org/doi/full/10.1056/NEJMoa2401424