MAYZENT is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

0.25 mg tablet: Pale red, unscored, round biconvex film-coated tablet with beveled edges, debossed with

1 mg tablet: Violet white, unscored, round biconvex film-coated tablet with beveled edges, debossed with

2 mg tablet: Pale yellow, unscored, round biconvex film-coated tablet with beveled edges, debossed with

MAYZENT is contraindicated in patients who have:

The following serious adverse reactions are described elsewhere in the labeling:

In patients with overdosage of MAYZENT, it is important to observe for signs and symptoms of bradycardia, which may include overnight monitoring. Regular measurements of pulse rate and blood pressure are required, and ECGs should be performed

There is no specific antidote to siponimod available. Neither dialysis nor plasma exchange would result in meaningful removal of siponimod from the body. The decrease in heart rate induced by MAYZENT can be reversed by atropine or isoprenaline.

MAYZENT tablets contains siponimod, an S1P receptor modulator, as 2:1 co-crystal of siponimod and fumaric acid and has the following chemical name:

1-[[4-[(1

Its structure is shown below:

It is a white to almost white powder.

MAYZENT is provided as 0.25 mg, 1 mg, and 2 mg film-coated tablets for oral use. Each tablet contains 0.25 mg, 1 mg, or 2 mg siponimod, equivalent to 0.28 mg, 1.11 mg, or 2.22 mg as 2:1 co-crystal of siponimod and fumaric acid, respectively.

MAYZENT tablets contain the following inactive ingredients: colloidal silicon dioxide, crospovidone, glyceryl dibehenate, lactose monohydrate, microcrystalline cellulose, with a film coating containing iron oxides (black and red iron oxides for the 0.25 mg and 1 mg strengths and red and yellow iron oxides for the 2 mg strength), lecithin (soy), polyvinyl alcohol, talc, titanium dioxide, and xanthan gum.

The efficacy of MAYZENT was demonstrated in Study 1, a randomized, double-blind, parallel-group, placebo-controlled, time-to-event study in patients with secondary progressive multiple sclerosis (SPMS) who had evidence of disability progression in the prior 2 years, no evidence of relapse in 3 months prior to study enrollment, and an Expanded Disability Status Scale (EDSS) score of 3.0 to 6.5 at study entry (NCT 01665144).

Patients were randomized to receive either once daily MAYZENT 2 mg or placebo, beginning with a dose titration

The primary endpoint of the study was the time to 3-month confirmed disability progression (CDP), defined as at least a 1-point increase from baseline in EDSS (0.5-point increase for patients with baseline EDSS of 5.5 or higher) sustained for 3 months. A prespecified hierarchical analysis consisted of the primary endpoint and 2 secondary endpoints, the time to 3-month confirmed worsening of at least 20% from baseline on the timed 25-foot walk test and the change from baseline in T2 lesion volume. Additional endpoints included annualized relapse rate (relapses/year) and MRI measures of inflammatory disease activity.

Study duration was variable for individual patients (median study duration was 21 months, range was 1 day to 37 months).

Study 1 randomized 1651 patients to either MAYZENT 2 mg (N = 1105) or placebo (N = 546); 82% of MAYZENT-treated patients and 78% of placebo-treated patients completed the study. Median age was 49.0 years, 95% of patients were white, and 60% female. The median disease duration was 16.0 years, and median EDSS score at baseline was 6.0 (56% of patients had ≥ 6.0 EDSS at baseline); 36% of patients had one or more relapses in the 2 years prior to study entry; 22% of those patients with available imaging had one or more gadolinium-enhancing lesions on their baseline MRI scan; 78% of patients had been previously treated with an MS therapy.

Results are presented in Table 4. MAYZENT was superior to placebo in reducing the risk of confirmed disability progression, based on a time-to-event analysis (hazard ratio 0.79,

*HR and 95% CI presented are model-based estimates for a range of values of age and Expanded Disability Status Scale (EDSS).

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Tell patients not to discontinue MAYZENT without first discussing this with the prescribing physician. Advise patients to contact their physician if they accidently take more MAYZENT than prescribed.

Instruct patients to administer tablets whole; do not split, crush, or chew MAYZENT tablets.

Inform patients that they may have an increased risk of infections, some of which could be life-threatening, when taking MAYZENT, and that they should contact their physician if they develop symptoms of infection

Inform patients that cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients who received MAYZENT. Inform the patient that PML is characterized by a progression of deficits and usually leads to death or severe disability over weeks or months. Instruct the patient of the importance of contacting their doctor if they develop any symptoms suggestive of PML. Inform the patient that typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes

Advise patients that MAYZENT may cause macular edema, and that they should obtain an eye exam near the start of treatment with MAYZENT, have their eyes monitored periodically by an eye care professional while receiving therapy, and contact their healthcare provider if they experience any changes in their vision while taking MAYZENT

Advise patients that initiation of MAYZENT treatment results in transient decrease in heart rate

Advise patients that they should contact their physician if they experience new onset or worsening of dyspnea

Inform patients that MAYZENT may increase liver enzymes. Advise patients that they should contact their physician if they experience any unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine during treatment

Inform patients that the risk of BCC and SCC is increased with the use of MAYZENT and that cases of melanoma have been reported. Advise patients that any suspicious skin lesions should be promptly evaluated. Advise patients to limit exposure to sunlight and ultraviolet light by wearing protective clothing and using a sunscreen with a high protection factor

Inform patients that, based on animal studies, MAYZENT may cause fetal harm

Instruct patients that if they are pregnant or plan to become pregnant while taking MAYZENT, they should inform their healthcare provider. Encourage patients to enroll in the MotherToBaby Pregnancy Study in Multiple Sclerosis if they become pregnant while taking MAYZENT

Advise patients to immediately report to their healthcare provider any symptoms involving sudden onset of severe headache, altered mental status, visual disturbances, or seizure. Inform patients that delayed treatment could lead to permanent neurological sequelae

Inform patients that severe increase in disability has been reported after discontinuation of another S1P receptor modulator like MAYZENT. Advise patients to contact their physician if they develop worsening symptoms of MS following discontinuation of MAYZENT

Advise patients that MAYZENT continues to have effects, such as lowering effects on peripheral lymphocyte count, for up to 3 to 4 weeks after the last dose

Inform patients that MAYZENT may be stored at room temperature for up to 3 months. If patients need to store MAYZENT for more than 3 months, containers should remain unopened and stored in a refrigerator until use

Distributed by:

MAYZENT is a registered trademark of Novartis AG

© Novartis

T2025-51

NDC 0078-0979-50

Rx only

MAYZENT

(siponimod) tablets

0.25 mg*

28 tablets

Dispense with accompanying Medication Guide.

NOVARTIS

NDC 0078-1014-15

Rx only

MAYZENT

(siponimod) tablets

1 mg*

30 tablets

Dispense with accompanying Medication Guide.

Swallow tablets whole. DO NOT split tablets.

NOVARTIS

NDC 0078-0986-15

Rx only

MAYZENT

(siponimod) tablets

2 mg*

30 tablets

Dispense with accompanying Medication Guide.

Swallow tablets whole. DO NOT split tablets.

NOVARTIS