Obstructive hypertrophic cardiomyopathy (oHCM)

Active Ingredient: Aficamten

Indication for Aficamten

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

Aficamten is indicated for the treatment of symptomatic (New York Heart Association, NYHA, class II-III) obstructive hypertrophic cardiomyopathy (oHCM) in adult patients.

For this indication, competent medicine agencies globally authorize below treatments:

5 mg initial dose with subsequent increase every 2-8 weeks by 5 mg until maintenance dose or maximum dose of 20 mg is reached

For:

Dosage regimens

Oral, 5 milligrams aficamten, once daily, over the duration of 2 to 8 weeks. Afterwards, oral, 10 milligrams aficamten, once daily, over the duration of 2 to 8 weeks. Afterwards, oral, 15 milligrams aficamten, once daily, over the duration of 2 to 8 weeks. Afterwards, oral, 20 milligrams aficamten, once daily. The maximum allowed total dose is 20 milligrams aficamten daily.

Detailed description

Treatment should be initiated under the supervision of a physician experienced in the management of patients with cardiomyopathy.

Before treatment initiation, left ventricular ejection fraction (LVEF) should be assessed by echocardiography. Initiation or up-titration of aficamten in patients with LVEF <55% is not recommended. Regular LVEF and Valsalva left ventricular outflow tract gradient (LVOT-G) assessment should be performed during titration to achieve an appropriate target Valsalva LVOT-G, while maintaining LVEF ≥50%.

Posology

The dose range is 5 mg to 20 mg (either 5 mg, 10 mg, 15 mg, or 20 mg). The recommended starting dose is 5 mg orally once daily. A starting dose of 10 mg should be considered for patients with LVOT-G ≥100 mmHg. The dose should be increased every 2 to 8 weeks by 5 mg until a maintenance dose or the maximum dose of 20 mg is achieved. The maintenance dose is individualised based on the patient's LVEF and LVOT-G. Recommendations for dosing based on LVEF and LVOT-G criteria are in the following table.

Dose adjustment of aficamten:

LVEFValsalva LVOT-GDose adjustment
≥55%≥30 mmHgIncrease dose by 5 mg
(up to the maximum dose of 20 mg once daily)
≥55%<30 mmHgMaintain dose
<55% and ≥50%AnyMaintain dose
<50% and ≥40%AnyDecrease dose by 5 mg1

Interrupt treatment for 7 days for 5 mg dose
<40%AnyInterrupt treatment for at least 7 days.

1 Dose decrease as follows: from 20 mg to 15 mg; from 15 mg to 10 mg; from 10 mg to 5 mg

An echocardiographic assessment should be performed 2 to 8 weeks after initiation of treatment, any dose adjustment, or treatment interruption. After a treatment interruption when LVEF <40%, treatment should be resumed with a dose reduced by 5 mg when LVEF ≥55%. If at 5 mg and LVEF <50%, treatment should be interrupted for 7 days, and treatment can be resumed at 5 mg when LVEF ≥55% (see table).

After the maintenance dose has been established, LVEF and Valsalva LVOT-G should be assessed every 6 months, or every 3 months in patients with LVEF ≥50% to <55%. Consider monitoring LVEF and adjust dose per Table 1, as needed, in patients with intercurrent illness (e.g. severe infection or COVID-19), new arrhythmia (e.g. new or uncontrolled atrial fibrillation or other uncontrolled tachyarrhythmia) or any other conditions that may impair systolic function. Dose increases are not recommended until intercurrent illness or new arrythmia has resolved or stabilised.

Discontinuation of aficamten may result in recurrence of HCM symptoms. Gradual dose reduction may attenuate the rate of symptom recurrence following treatment discontinuation.

Missed doses

If a dose is missed, it should be taken as soon as possible on the same day. The next scheduled dose should be taken at the usual time the following day. Two doses should not be taken the same day.

Elderly

No dose adjustment is required for patients aged 65 years and older.

Dosage considerations

Treatment should be taken once daily with or without meals.

Active ingredient

Aficamten

Aficamten is a reversible allosteric cardiac myosin inhibitor that binds directly to the motor domain of cardiac myosin and prevents it from entering the force-producing state. It is designed to reduce the hypercontractility in the cardiac sarcomere fundamental to the pathophysiology of hypertrophic cardiomyopathy (HCM). The consequent reduction in cardiac contractility reduces left ventricular outflow tract (LVOT) obstruction in HCM patients.

Read more about Aficamten

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