MAYZENT

What it is

Mayzent contains siponimod as its active ingredient. It is available as film-coated tablets containing 0.25 mg, 1 mg or 2 mg siponimod (as siponimod hemifumarate). Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. Mayzent is subject to additional monitoring in Australia to allow quick identification of new safety information.

Approved indications —

Secondary progressive multiple sclerosis (SPMS) in adult patients

Dosing overview

Treatment initiation requires a 5-day titration pack, starting with 0.25 mg once daily on days 1 and 2, followed by 0.5 mg on day 3, 0.75 mg on day 4, and 1.25 mg on day 5, to reach the maintenance dose of 2 mg starting on day 6. During the first 6 days of treatment, the recommended daily dose should be taken once daily in the morning with or without food. The recommended maintenance dose of Mayzent is 2 mg taken once daily with or without food. In patients with a CYP2C9*2*3 or *1*3 genotype, the recommended maintenance dose is 1 mg taken once daily. If maintenance treatment is interrupted for 4 or more consecutive daily doses, treatment must be re-initiated with a new titration pack. Treatment interruptions for up to 3 missed consecutive daily doses do not require re-titration.

Key safety warnings

Mayzent causes a dose-dependent reduction of peripheral lymphocyte count to 20 to 30% of baseline values due to reversible sequestration of lymphocytes in lymphoid tissues. This immune system effect may increase the risk of infections. Initiation of treatment should be delayed in patients with severe active infection until resolution. Cases of cryptococcal meningitis have been reported with Mayzent. Physicians should be vigilant for clinical symptoms or signs, and Mayzent treatment should be suspended until the condition has been excluded. Cases of progressive multifocal leukoencephalopathy have been reported for S1P receptor modulators including Mayzent. If PML is suspected, Mayzent treatment should be suspended until PML has been excluded. Macular oedema was more frequently reported on siponimod (1.8%) than on placebo (0.2%), with the majority of cases occurring within the first 3 to 4 months of therapy. An ophthalmic evaluation of the fundus, including the macula, is recommended in all patients before starting treatment and at any time if there is any change in vision while taking Mayzent. Since initiation of Mayzent treatment results in a transient decrease in heart rate, an up-titration scheme is applied at treatment start. Initiation of Mayzent treatment has been associated with transient atrioventricular conduction delays, manifesting in most cases as first-degree atrioventricular blocks. As a precautionary measure, patients with sinus bradycardia, first or second-degree atrioventricular block, or a history of myocardial infarction or heart failure should be observed for 6 hours after the first dose for signs and symptoms of bradycardia, with electrocardiograms obtained prior to dosing and at the end of the observation period. Hypertension was more frequently reported in patients on siponimod (12.6%) than on placebo (9.0%), with treatment resulting in an increase of systolic and diastolic blood pressure reaching maximum effect after approximately 6 months. Blood pressure should be monitored during treatment with Mayzent and managed appropriately.

Contraindications

Mayzent should not be administered to patients with known hypersensitivity to siponimod or any of the excipients. Mayzent is contraindicated in patients with a CYP2C9*3/*3 genotype. Mayzent should not be given to patients who in the last 6 months had myocardial infarction, unstable angina pectoris, stroke/transient ischemic attack, decompensated heart failure (requiring inpatient treatment), or New York Heart Association Class III/IV heart failure. Mayzent should not be administered to patients with second-degree Mobitz type II atrioventricular block, third-degree atrioventricular block, sino-atrial heart block or sick-sinus syndrome, if they do not have a pacemaker.

PBS listing

Mayzent was recommended by the PBAC in July 2020 for multiple sclerosis (secondary progressive MS who are ambulant with a history of relapsing forms of MS). In March 2024, the PBAC recommended a change for a new strength for relapsing-remitting multiple sclerosis.

Regulatory history

Mayzent was approved on 25 October 2019 for the treatment of adult patients with secondary progressive multiple sclerosis. This decision addressed a high unmet medical need for effective treatments in this patient population. The 0.25 mg and 2 mg film-coated tablet blister packs were first listed on the ARTG on 1 November 2019. The 1 mg film-coated tablet blister pack was first listed on 20 July 2023. The PBAC recommended Mayzent in July 2020 and recommended a change in March 2024 for a new strength for relapsing-remitting multiple sclerosis.