Mayzent® (Siponimod) Tablets Approved by the FDA for Adults with Relapsing Forms of MS, Including Active SPMS
In a news release dated March 26, 2019, the United States Food and Drug Administration (FDA) announced the approval of Mayzent® (siponimod) oral tablets to treat adults with relapsing forms of multiple sclerosis (MS). The approval includes individuals with clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary-progressive MS (SPMS). Mayzent is the only disease-modifying therapy (DMT) to be approved in recent years for active secondary-progressive MS.
According to Novartis, the makers of Mayzent, the medication is expected to be available in the United States in approximately one week (early April). Patients will not require a first-dose observation (FDO) to monitor for cardiac events upon initiation, unless they have certain pre-existing cardiac conditions.
According to MSAA’s Chief Medical Consultant Dr. Jack Burks, “The FDA approval of Mayzent for wide-ranging forms of MS – including active SPMS, RRMS, and CIS – is very good news for members of the MS community. The lack of first-dose cardiac events and the fact that it will soon be available both add to the good news. MSAA, the medical community, and those affected by MS, are greatly pleased to hear of this exciting new approval.”
The FDA’s press release explains that most people with MS start with a relapsing-remitting course of symptom flare-ups and remissions, possibly with some degree of residual disability. Over time, some patients experience an increase in disability that is independent of relapses, and this is referred to as “secondary-progressive MS.” Initially, people with this form of MS may still experience relapses, which is referred to as “active” secondary-progressive MS – the form that Mayzent is approved to treat. Without treatment, many of those with this form of MS eventually experience continued progression of disability without relapses, and this is referred to as “non-active” secondary-progressive MS. Mayzent is not approved for this latter form of the disease.
According to MSAA’s MS Research Update 2018, siponimod is a drug with a mechanism of action similar to Gilenya® (fingolimod). Like Gilenya, it works at the S1P receptor family to block the movement of lymph cells from lymph nodes; however, siponimod appears to interact with fewer of the receptors than Gilenya does – with its primary actions at the S1P1 and the S1P5 receptors. Siponimod has a relatively short half-life compared to Gilenya, which means that the drug does not stay in the body as long. Researchers hope that these small differences will minimize cardiac issues.
The approval was based on the results of the EXPAND trial, a Phase III, multi-national study of siponimod involving more than 1,600 people with secondary-progressive MS. Results of the study were published in The Lancet in March 2018. The participants were randomized in a 2:1 ratio to receive siponimod or placebo. The trial was scheduled to run for three years or until a pre-specified number of confirmed disability progression events (CDP) occurred. The primary endpoint was time to three-month CDP.
The study found that, relative to placebo, siponimod reduced the risk of three-month CDP by 21 percent, cut the risk of six-month CDP by 26 percent, slowed the rate of brain volume loss by 23 percent, and reduced the annual relapse rate by 55 percent. No significant difference was found between siponimod and placebo in terms of two walking tests studied in the trial. Novartis notes that the EXPAND trial also showed significant favorable outcomes in other relevant measures of MS disease activity, including cognition, reduced disease activity as shown on MRI, and reduced brain-volume loss (brain shrinkage).
Eighteen percent of patients in the siponimod group and 15 percent of those receiving placebo experienced serious adverse events. A decrease in white blood cells, heart rate, and rhythm abnormalities, as well as hypertension, swelling of the macula of the eye, varicella zoster reactivation, and convulsions occurred more often in patients receiving siponimod than in those in the placebo group. The rate of infections, cancer, and death did not differ between the groups, and adjusting the initial dose of siponimod mitigated cardiac effects seen in early treatment with the medication.
According to the FDA, Mayzent must be dispensed with a patient Medication Guide, providing important information about how the medication is used as well as potential risks. Patients taking Mayzent need to be monitored for changes in vision caused by macular edema, transient decreases in heart rate, decline in lung function, and changes in liver enzymes, which also need to be checked prior to starting the drug. Blood pressure should be monitored during treatment, and women who could become pregnant should use contraception during and for 10 days after stopping treatment to avoid potential risk of fetal harm. Healthcare professionals will need to monitor for other risks as well. Headache, high blood pressure, and changes in liver function tests were the most common adverse reactions reported by individuals taking Mayzent.
For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.
Written by Susan Wells Courtney, MSAA Senior Writer
Reviewed by Dr. Jack Burks, MSAA Chief Medical Consultant