The United Kingdom’s Medicines and Healthcare products Regulatory Agency has authorised Cytokinetics’ once-daily aficamten for eligible adults with symptomatic obstructive hypertrophic cardiomyopathy, while the National Institute for Health and Care Excellence has recommended the medicine for use in England and Wales. The recommendation covers adults with New York Heart Association class II or III symptoms and could make treatment available to approximately 6,600 people in England. Aficamten directly reduces excessive heart-muscle contraction, but patients will still require echocardiographic monitoring because excessive myosin inhibition can weaken the heart’s pumping function.
Who can receive aficamten under the new NICE recommendation
NICE recommends aficamten as an option for adults with symptomatic obstructive hypertrophic cardiomyopathy whose symptoms fall within NYHA class II or III. Class II generally describes patients whose ordinary physical activity causes some limitation, while class III reflects more substantial limitation during less-than-ordinary activity.
The medicine can be added to individually optimised standard care, including beta-blockers, non-dihydropyridine calcium-channel blockers or disopyramide. It may also be used alone when those treatments are contraindicated. Cytokinetics must provide aficamten under the confidential commercial arrangement agreed with the National Health Service.
The MHRA marketing authorisation applies across the United Kingdom, while NICE’s recommendation establishes funded access in England and Wales. NHS England is expected to make the medicine available within 30 days of the final guidance, and Cytokinetics has said eligible patients should begin gaining access later in 2026. Separate reimbursement processes may still influence availability in Scotland and Northern Ireland.
NICE used a cost-comparison approach rather than conducting a completely new cost-effectiveness assessment against every available therapy. Cytokinetics therefore had to demonstrate that the total cost of aficamten was similar to or lower than the cost of mavacamten, the other cardiac myosin inhibitor already recommended for this population. The confidential discount means the actual NHS acquisition price has not been publicly disclosed.
The cost-comparison decision should not be interpreted as evidence that aficamten is clinically superior to mavacamten. The two medicines have not been compared directly in a completed head-to-head clinical trial. NICE concluded that aficamten was likely to provide broadly comparable effectiveness while offering another treatment option within the same disease-specific class.
How aficamten reduces obstruction caused by an excessively contracting heart
Hypertrophic cardiomyopathy causes the heart muscle to become abnormally thick. In the obstructive form, the thickened muscle and abnormal movement of the mitral valve narrow the pathway through which blood leaves the left ventricle. Patients may experience breathlessness, fatigue, dizziness, chest pain, fainting or reduced exercise capacity.
Aficamten is a reversible cardiac myosin inhibitor. It binds to cardiac myosin and reduces the number of myosin molecules entering a force-producing state during each heartbeat. This lowers excessive contraction at the level of the cardiac sarcomere and can reduce the pressure gradient across the left ventricular outflow tract.
The mechanism differs from conventional symptom-management medicines. Beta-blockers and calcium-channel blockers primarily influence heart rate and filling, while aficamten acts more directly on the hypercontractility contributing to obstruction.
The medicine is taken once daily and is available as 5 mg, 10 mg, 15 mg and 20 mg tablets. Treatment is individually adjusted using echocardiographic measurements of left ventricular ejection fraction and outflow-tract obstruction. Aficamten begins reducing obstruction relatively quickly, with pharmacodynamic changes observed within two weeks in the pivotal trial.
Reducing contraction too much can produce systolic dysfunction or heart failure. Clinicians must therefore balance relief of obstruction against preservation of adequate pumping function. Echocardiograms are required before and during treatment, even though the UK authorities indicated that some patients may need fewer early monitoring scans than patients initiating mavacamten.
That possible monitoring advantage may reduce the burden on patients and specialist cardiac services, but it does not eliminate the need for structured surveillance. Dose adjustments may also be necessary when patients begin or stop medicines that alter aficamten metabolism, including certain antifungal, psychiatric and antiseizure treatments.
SEQUOIA-HCM showed improved exercise capacity after 24 weeks
The MHRA authorisation was supported primarily by SEQUOIA-HCM, a randomized, double-blind and placebo-controlled Phase 3 trial involving 282 adults with symptomatic obstructive hypertrophic cardiomyopathy. Participants had NYHA class II or III symptoms, preserved ejection fraction and clinically important left ventricular outflow-tract obstruction at enrollment.
Patients received aficamten or placebo once daily for 24 weeks. Aficamten treatment began at 5 mg, with doses adjusted at weeks two, four and six according to echocardiographic measurements. The maximum dose was 20 mg daily.
The primary endpoint was the change in peak oxygen uptake measured during cardiopulmonary exercise testing. Peak oxygen uptake provides an objective assessment of the amount of oxygen a person can use during maximal exercise and is reduced in many patients with symptomatic hypertrophic cardiomyopathy.
Peak oxygen uptake increased by approximately 1.8 millilitres per kilogram per minute in the aficamten group and did not meaningfully change in the placebo group. The adjusted treatment difference was approximately 1.7 millilitres per kilogram per minute, with a 95% confidence interval of 1.0 to 2.4 and a p-value below 0.001.
The improvement shows that aficamten increased exercise capacity over six months, but it does not establish that the medicine prevents sudden cardiac death, stroke, atrial fibrillation or progression to heart failure. Longer follow-up and post-authorisation evidence will be needed to determine whether reduced obstruction and improved symptoms lead to fewer major cardiovascular events.
The trial population also consisted of adults with obstructive disease and relatively preserved ejection fraction. The current approval should not be extended to children or patients with non-obstructive hypertrophic cardiomyopathy. Aficamten has been studied separately in those populations, but those uses require their own regulatory evaluations.
Systolic dysfunction remains the main safety issue requiring monitoring
The most commonly reported adverse reactions in the UK product information were hypertension in 7.7% of patients, palpitations in 7%, dizziness in 4.2% and systolic dysfunction in 3.5%.
Five aficamten-treated patients in SEQUOIA-HCM developed a left ventricular ejection fraction below 50%, compared with one patient receiving placebo. One treated patient had an asymptomatic ejection fraction below 40%. The reductions were described as reversible and were not associated with clinical heart failure or treatment interruption during the 24-week study.
The absence of clinical heart failure in the pivotal trial is reassuring but does not remove the underlying pharmacological risk. Cardiac myosin inhibitors intentionally reduce contractility, and the same mechanism responsible for relieving obstruction can impair systolic function when exposure is excessive or a patient becomes medically unstable.
Intercurrent illness, changes in rhythm and interacting medicines may alter the safety balance. Clinicians should reassess patients who develop new breathlessness, chest discomfort, fatigue, swelling, fainting or symptoms suggesting deteriorating heart function.
Aficamten is subject to additional monitoring in the United Kingdom, allowing regulators to identify new or uncommon adverse reactions as use expands beyond clinical trials. Healthcare professionals and patients are encouraged to report suspected side effects through the MHRA Yellow Card system.
The simultaneous MHRA authorisation and NICE recommendation shorten the interval between regulatory approval and funded access. For eligible patients, aficamten introduces a second disease-specific myosin inhibitor and another option when standard medicines do not adequately control obstruction and symptoms.
Its long-term clinical position will depend on real-world safety, adherence, monitoring burden and how consistently improvements in exercise capacity translate into meaningful daily functioning. The new recommendation establishes access, but continued surveillance will determine whether aficamten can maintain reduced obstruction without causing clinically important loss of cardiac pumping strength.
