Mayzent (siponimod) is an approved oral treatment for multiple sclerosis (MS) that works to reduce the frequency of relapses and delay the progression of disability by modulating the body’s immune response. It also can help prevent the development of new brain lesions.
The therapy was developed by Novartis and is indicated for adults with relapsing forms of MS.
In MS, the immune system mistakenly attacks the myelin sheath, an insulating layer that surrounds nerve fibers, in the brain and spinal cord.
Mayzent is a modulator of the sphingosine 1-phosphate (S1P) receptors, which are found on the surface of some immune cells and are important for controlling the migration of these cells from lymph nodes — where they are matured and stored — to the blood.
By modulating the S1P receptors, Mayzent can trap immune cells in lymph nodes, which prevents these cells from getting into the brain or spinal cord and causing damaging inflammation.
As S1P receptors also are found on some cells in the brain and spinal cord, Mayzent may provide other neuroprotective effects beyond blocking immune cell migration. For example, it can modulate S1P receptors on the outside of oligodendrocytes, the cells chiefly responsible for making myelin, and attenuate the loss of myelin. Research in a mouse model of MS also indicates that Mayzent acts directly in the brain and spinal cord to prevent nerve cell damage.
The U.S. Food and Drug Administration approved Mayzent in 2019 for patients 18 and older with relapsing MS types, which include clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).
In the European Union, as well as in Canada, Australia, and several other countries, Mayzent is only approved to treat adults with SPMS and active disease, defined by the presence of relapses or brain lesions with active inflammation.
Mayzent is not recommended for the following groups of patients:
The therapy is available in film-coated tablets that come in three strengths:
The recommended dose of Mayzent is 2 mg, taken orally once a day. However, patients starting on the medication, or restarting it after missing at least four consecutive doses, will receive gradually increasing doses over the first six days. This entails a 0.25 mg dose over days 1 and 2, a 0.50 mg dose on day 3, a 0.75 mg dose on day 4, and a 1.25 mg dose on the final day of this titration step. On day 6, patients begin the 2 mg recommended dose.
In individuals who have the CYP2C9*3 variation in one copy (but not two) of the CYP2C9 gene, Mayzent’s recommended dose is 1 mg daily. These patients also require adjustments in their treatment initiation regimen.
The medication should be swallowed whole, and not split, crushed, or chewed. It can be taken with or without food.
Because initiation of Mayzent treatment may cause a decrease in heart rate, it is recommended that patients with certain heart conditions have their pulse and blood pressure monitored regularly for six hours after the first dose.
A Phase 2 trial (NCT00879658) called BOLD, sponsored by Novartis, investigated Mayzent against a placebo in 297 adult RRMS patients. Participants received ascending doses of Mayzent — 0.25 or 1.25 mg for three months, or 0.5, 2, or 10 mg for six months — or a placebo, once daily.
In this trial, most Mayzent doses reduced the number of active brain lesions compared with a placebo, with the 2 mg dose reducing the number of new or enlarging brain lesions after six months by 80%. While the trial was not designed to assess an effect on relapses, patients on this dose also experienced a significant reduction in their annualized relapse rate. Specifically, the relapse rates were 0.20 for patients taking Mayzent versus 0.58 for those on the placebo.
Data from an extension study (NCT01185821) in which participants could continue to receive Mayzent for two more years, showed that the treatment also reduced the number of brain lesions with active inflammation. Relapse rates remained low across treatment groups throughout the trial, but were less frequent with the higher doses of the therapy.
Mayzent’s approval was based on data from the EXPAND Phase 3 trial (NCT01665144), also sponsored by Novartis, which enrolled 1,651 SPMS patients with no evidence of relapse in the past three months. For up to three years, participants received either a 2 mg dose of Mayzent, or a placebo, once daily.
Results showed that the treatment significantly reduced the risk of three-month confirmed disability progression by 21%, and lowered relapse rates by 55%, compared with a placebo. The therapy also reduced the number of new or enlarging brain lesions and inflammatory lesions by more than 80%, and resulted in smaller changes in brain volume.
Additional analyses showed that Mayzent improved cognitive processing speed in the trial, and reduced the likelihood that treated patients would require a wheelchair.
A long-term extension of EXPAND is now underway, with patients receiving the 2 mg dose of the therapy for about seven additional years. Data from the extension still showed a significantly lower risk of confirmed disability progression and reduced relapse rate in patients on continuous Mayzent, compared with those who were initially on a placebo in the main trial.
Novartis is currently running a Phase 3 trial (NCT04926818), called NEOS, that is assessing the safety and efficacy of Mayzent along with the company’s injectable medication Kesimpta (ofatumumab). This trial involves 180 children and adolescents, ages 10 to 17. The two therapies are being tested against Gilenya (fingolimod), an MS medication also from Novartis that is approved for people ages 10 and older.
While the primary goal is to explore the treatments’ effects on relapse rates, investigators also will examine the number of brain lesions, changes in biomarkers of nerve damage, and safety.
The company also is sponsoring EXCHANGE, an open-label Phase 3 trial (NCT03623243) that is testing Mayzent in people who switched from other disease-modifying therapies due to evidence of MS progression. About 400 participants with relapsing forms of MS are expected to take part and receive the therapy for six months.
The main goal of this trial is to determine the safety of switching to Mayzent from other therapies. Secondary goals include patient satisfaction and adherence to Mayzent as a daily treatment.
The most common side effects of Mayzent include:
Mayzent can cause abnormal heart rates and increase blood pressure. Heart health should be checked before starting on the medication, and patients with some conditions may require monitoring after taking the first dose of Mayzent.
The medication also can decrease lung function and lead to shortness of breath, which should be checked if appropriate.
Treatment with Mayzent can cause damage to the liver. Markers of liver health should be assessed prior to starting treatment and also if patients show any signs of liver damage. The therapy should be ceased if significant liver injury is confirmed.
Because Mayzent reduces the number of immune cells in circulation, it has been linked with an increased risk of infections. Patients should have their blood cell counts checked prior to starting on the medication, and be regularly monitored for infections while on Mayzent and for four weeks after stopping treatment. The medication should not be taken by people with an active infection.
Vaccines containing live viruses should be avoided while on Mayzent. Patients who have no history of chickenpox or records of receiving a vaccine for chickenpox are recommended to receive a full course of vaccination against the varicella zoster virus at least one month prior to Mayzent initiation.
A form of swelling in the eye called macular edema may occur during treatment with Mayzent. This issue is more common in people with diabetes or a form of eye inflammation called uveitis. A full ophthalmic evaluation should be performed before starting on the medication and at any time if patients experience a change in vision.
A neurological disorder called posterior reversible encephalopathy syndrome has been reported in some people treated with Mayzent. This disorder causes symptoms such as severe headache, changes in mental status, impaired vision, and seizures, which can evolve into stroke and permanent neurological damage if not treated adequately.
Some forms of skin cancer, such as basal cell carcinoma, melanoma, and squamous cell carcinoma, may occur in people on Mayzent. Patients are advised to follow usual guidelines for people at high risk of skin cancer, such as limiting sun exposure, wearing adequate clothing, and using sunscreen. If a suspicious lesion appears, it should be promptly evaluated.
Based on animal studies, Mayzent can cause damage to a developing fetus. It is recommended that people with the potential to become pregnant use effective contraception while on the therapy and for at least 10 days after stopping it.
Individuals who become pregnant while on Mayzent may enroll in a Novartis-sponsored registry (NCT04933552) that is monitoring outcomes in patients and infants exposed to the medication during pregnancy.
It is not known if Mayzent passes into breast milk. Patients who are breastfeeding or plan to breastfeed while on the medication are advised to discuss this topic with their healthcare team.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Mayzent was approved by the U.S. Food and Drug Administration in March 2019 to treat adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting multiple sclerosis, and active secondary progressive multiple sclerosis.
Animal studies suggest that Mayzent can cause damage to a developing fetus. Anyone with the capacity to become pregnant should use effective birth control methods while on Mayzent and for 10 days after ceasing treatment.
Interactions between alcohol and Mayzent have not been reported. However, both can cause damage to the liver, and alcohol is also known to interfere with some disease symptoms and medications. It is recommended that patients discuss safe alcohol use with their healthcare team.
Benefits may be seen by some patients as soon as six months after starting treatment. In the BOLD trial, which compared Mayzent against a placebo in people with relapsing-remitting multiple sclerosis, significant reductions in the number of brain lesions and in relapse frequency were observed in as little as six months. However, as each person may respond very differently to a given medication, patients should talk with their care team to understand how Mayzent could help in their specific case.
Neither hair loss nor weight gain has been reported in clinical trials as side effects of Mayzent. Patients are advised to speak with their healthcare provider if they experience any unusual symptoms while on the medication.
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