CAMZYOS

What it is

CAMZYOS contains mavacamten, a selective, allosteric, and reversible cardiac myosin inhibitor. The medicine is available in hard capsule formulations containing 2.5 mg, 5 mg, 10 mg, or 15 mg of mavacamten. Mavacamten modulates the number of myosin heads that can enter power-generating states, thus reducing, or in hypertrophic cardiomyopathy (HCM) normalising, the probability of force-producing systolic and residual diastolic crossbridge formation. In HCM patients, myosin inhibition with mavacamten normalises contractility, reduces dynamic left ventricular outflow tract (LVOT) obstruction, and improves cardiac filling pressures and biomarkers of cardiac stress, improving symptoms and exercise capacity.

Approved indications

— Treatment of adults with symptomatic NYHA class II–III obstructive hypertrophic cardiomyopathy.

Dosing overview

The recommended starting dose of CAMZYOS is 5 mg orally once daily. The patient's individualised daily dose will be either 2.5, 5, 10, or 15 mg, with a maximum dose of 15 mg once daily. Treatment with mavacamten should be initiated and supervised by a specialist cardiologist, or consultant physician with experience in the management of obstructive HCM. It is important to regularly monitor the patient's symptoms of obstructive HCM, LVOT gradient with Valsalva manoeuvre and left ventricular ejection fraction (LVEF) using echocardiogram assessments, and follow the algorithms for initiation and maintenance for appropriate CAMZYOS dosing and monitoring schedules. Initiation of CAMZYOS in patients with LVEF less than 55% is not recommended. CAMZYOS should be interrupted if LVEF is less than 50% at any visit.

Key safety warnings

CAMZYOS reduces left ventricular ejection fraction (LVEF), and prior to and during treatment, regular clinical and echocardiogram monitoring are required to appropriately titrate and maintain the optimal patient dose. CAMZYOS reduces LVEF and may cause heart failure with reduced ejection fraction (HFrEF) defined as symptomatic LVEF less than 50%. Patients with a serious intercurrent illness such as serious infections or arrhythmia (including atrial fibrillation or other uncontrolled tachyarrhythmia) or those undergoing major cardiac surgery may be at greater risk of systolic dysfunction and progress to heart failure. New or worsening dyspnoea, chest pain, fatigue, palpitations, leg oedema or elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be signs and symptoms of a reduced LVEF and should prompt an evaluation of cardiac function. Concomitant use of CAMZYOS with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction. Prior to and during CAMZYOS treatment, the potential for drug interactions, including over-the-counter medications (such as omeprazole or esomeprazole), should be considered. Based on animal studies, mavacamten may cause embryo-fetal harm when administered to a pregnant woman. Women of childbearing potential and women becoming pregnant while receiving the treatment should be informed of the potential risk to the fetus. Women of childbearing potential have to use highly effective contraception during treatment with CAMZYOS and for at least 4 months after discontinuing treatment.

Contraindications

CAMZYOS is contraindicated in patients with hypersensitivity to mavacamten or to any of the excipients. The use of CAMZYOS is contraindicated with strong CYP2C19 inhibitors, and with moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.

PBS listing

CAMZYOS is listed on the PBS in capsule strengths of 2.5 mg, 5 mg, 10 mg, and 15 mg, with authority required restriction and an ex-manufacturer price of A$2160.70 per item.

Regulatory history

CAMZYOS (mavacamten capsules in strengths of 2.5 mg, 5 mg, 10 mg, and 15 mg) was first registered on the ARTG on 19 September 2022. The AusPAR approval date was 15 September 2022 for the indication of treatment of adults with symptomatic NYHA class II–III obstructive hypertrophic cardiomyopathy. The PBAC considered CAMZYOS in November 2022 and July 2023 with not recommended outcomes. In November 2023, CAMZYOS was recommended by the PBAC for listing for treatment of adults with symptomatic obstructive HCM, with significant benefit over standard of care and cost-effectiveness achieved with price reduction.