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Mayzent

Mayzent(siponimod) is a disease-modifying drug by Novartis that can be used in patients with relapsing forms of multiple sclerosis (MS).¹

The treatment was approved by the US Food and Drug Administration in March 2019 for adult patients with relapsing forms of MS, including active secondary progressive multiple sclerosis (SPMS), relapsing-remitting multiple sclerosis (RRMS), and clinically isolated syndrome (CIS).² The safety and effectiveness of the treatment in pediatric patients are unknown.¹

It has also been approved by the European Medicines Agency for patients with active MS with signs of inflammation because it delays secondary disease progression. It has been authorized to be marketed across the EU since January 2020.³

Mayzent is a film-coated oral tablet. Treatment should start with a 5-day titration period; patients receive 0.25 mg on days 1 and 2, 0.5 mg on day 3, 0.75 mg on day 4, and 1.25 mg on day 5. This should be followed by a maintenance dose of 2 mg per day starting on day 6.⁴ It is recommended for patients with CYP2C9 genotypes *1/*1, *1/*2, or *2/*2, so patients should be assessed for CYP2C9 genotype.

Mayzent’s Mechanism of Action

Multiple sclerosis is an autoimmune disease of unknown etiology characterized by immune-mediated demyelination and axonal damage, which leads to a variety of symptoms and progressive disability.

Mayzent is a selective sphingosine-1-phosphate (S1P) receptor modulator.⁵ It acts by blocking the migration of lymphocytes from the lymph nodes to the central nervous system (CNS), thereby limiting the damage caused to the brain and spinal cord, and reduces CNS inflammation.

Get detailed prescribing information on the Mayzent monograph page on Rare Disease Advisor.

Warnings, Precautions, and Adverse Reactions

Mayzent can cause serious side effects, including bradycardia or bradyarrhythmia, and increase the risk of serious infections that can be life-threatening by lowering lymphocytes in the blood.¹ It can also lead to macular edema, hypertension, liver problems, respiratory problems, posterior reversible encephalopathy syndrome, and malignancies such as basal cell carcinoma (BCC), melanoma, and squamous cell carcinoma.

The most common side effects and clinical findings following Mayzent treatment are headaches, hypertension, and abnormal liver tests.

The symptoms of MS and disability can severely worsen following the discontinuation of Mayzent treatment.

Mayzent is contraindicated in patients with a CYP2C9*3/*3 genotype and those with a history of heart attack, unstable angina, transient ischemic attack (TIA), or certain types of heart failure in the last 6 months. It is also contraindicated in patients with certain types of heart block or arrhythmia.

Mayzent may cause harm to a fetus. As a result, effective contraception should be used while Mayzent treatment is ongoing and for at least 10 days following discontinuation of treatment. It is not known whether Mayzent passes into breast milk, so women on Mayzent treatment should avoid breastfeeding.

Efficacy in Clinical Trials

The safety and efficacy of Mayzent have been investigated in a phase 3 clinical trial titled EXPAND.⁶ The multicenter, randomized, double-blind, parallel-group, placebo-controlled study recruited 1645 patients aged 18 to 60 years with SPMS at 289 locations across 31 countries and randomly assigned them to either receive Mayzent at 0.25, 0.5, 1, or 2 mg or a placebo.

The primary endpoint of the study was the percentage of participants with 3-month confirmed disability progression events as measured by the Expanded Disability Status Scale (EDSS). Secondary endpoints included the efficacy of Mayzent relative to placebo in confirmed worsening on the 25-foot walk test, reducing the increase in T2 lesion volume on magnetic resonance imaging, annualized relapse rate and time to the first relapse, the delay in time to confirmed disability progression as measured by EDSS, the overall response rate on the 12-Item MS walking scale (MSWS-12), and the effect on 3-month confirmed disability progression as defined by EDSS in predefined subgroups.

The results of the study showed that Mayzent treatment reduced the risk of disability progression with a safety profile similar to that of other selective S1P receptor modulators.⁷ Long-term data from the study showed that patients with SPMS who were continuously treated with Mayzent had a lower risk of disability progression and cognitive decline compared to those who delayed Mayzent treatment. Mayzent also reduced cortical grey matter and thalamic atrophy, which are associated with long-term irreversible disability accumulation.⁸

Another phase 3 clinical trial, EXCHANGE, is currently recruiting an estimated 400 participants, aged 18 to 65 years, with advancing relapsing MS and an EDSS score between 2.0 and 6.5 at 70 sites in the US and 1 site in Puerto Rico.⁹ The trial aims to assess the safety and tolerability of conversion to Mayzent from another approved relapsing MS disease-modifying treatment.

The primary endpoint of the study is the number of patients with treatment-emergent adverse events. Secondary endpoints are the number of patients satisfied with treatment as measured by the Treatment Satisfaction Questionnaire for Medication, any changes in heart rate from baseline, and any complications arising as a result of Mayzent treatment.

The trial is expected to be completed in January 2022.

References

Mayzent® (siponimod) tablets. Novartis. Accessed June 15, 2021.
Mayzent FDA approval history. Drugs.com. Updated April 10, 2019. Accessed June 15, 2021.
Mayzent: siponimod. European Medicines Agency. January 23, 2020. Updated January 14, 2021. Accessed June 15, 2021.
Mayzent dosage. Drugs.com. Accessed June 15, 2021.
Mechanism of action. Novartis. Accessed June 15, 2021.
Exploring the efficacy and safety of siponimod in patients With secondary progressive multiple sclerosis (EXPAND). ClinicalTrials.gov. August 15, 2012. Updated June 9, 2021. Accessed June 15, 2021.
Kappos L, Bar-Or A, Cree BAC, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):1263-1273. doi:10.1016/S0140-6736(18)30475-6
Novartis announces new Mayzent^® (siponimod) data show sustained effect in delaying disability for up to five years in patients with secondary progressive multiple sclerosis (SPMS). News release. Novartis; April 21, 2020.
Safety and tolerability of conversion from oral, injectable, or infusion disease modifying therapies to dose-titrated oral siponimod (Mayzent) in advancing RMS patients. (EXCHANGE). ClinicalTrials.gov. August 9, 2018. Updated June 7, 2021. Accessed June 15, 2021.

Reviewed by Debjyoti Talukdar, MD, on 7/1/2021.

Ozge Ozkaya, MSc, PhD

Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.

Multiple Sclerosis (MS)