Research News: FDA Approves Two New Oral Treatments for Relapsing Forms of MS, Including Active SPMS
Mayzent® (Siponimod) Tablets
In a 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 (CIS), relapsing-remitting MS (RRMS), and active secondary-progressive MS (SPMS). Mayzent is the first disease-modifying therapy (DMT) to be approved in recent years for active secondary-progressive MS.
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 similar to Gilenya® (fingolimod), working at the S1P receptor family to block the movement of lymph cells from lymph nodes; however, siponimod appears to interact with fewer receptors and does not stay in the body as long. Researchers hope that these small differences will minimize cardiac issues. According to Novartis, the makers of Mayzent, most patients will not require a first-dose observation (FDO) to monitor for cardiac events upon initiation.
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. Participants were randomized to receive siponimod or placebo. The study found that, relative to placebo, siponimod reduced the risk of three and six-month confirmed disability progression events (CDP), slowed the rate of brain volume loss, and reduced the annual relapse rate. The 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).
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. Women who could become pregnant should use contraception 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.
Mavenclad® (Cladribine) Tablets
In a release dated March 29, 2019, the United States Food and Drug Administration (FDA) announced the approval of Mavenclad® (cladribine) oral tablets to treat adults with relapsing forms of multiple sclerosis (MS). The approval is for individuals with relapsing-remitting MS (RRMS) and for individuals with active secondary-progressive MS (SPMS).
Mavenclad is not recommended for individuals with clinically isolated syndrome (CIS). According to the FDA, Mavenclad is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS.
Following the approval of Mayzent® (siponimod) oral tablets three days earlier, Mavenclad has become the second disease-modifying therapy (DMT) to be approved in recent years for active secondary-progressive MS. According to EMD Serono, the makers of Mavenclad, this medication “is the first and only FDA-approved treatment for RRMS and active SPMS that provides two years of proven efficacy with a maximum of 20 days of oral treatment, during a two-year period.” Following these first two years, no treatment is needed for Years 3 and 4.
According to MSAA’s MS Research Update 2018, cladribine selectively targets the immune system’s B cells and T cells, leading to depletion of those cells. This is followed by a distinct pattern of “reconstitution,” as new B cells and T cells are produced.
The FDA’s approval of Mavenclad was based on the 96-week, Phase III CLARITY trial, where 1,326 patients with RRMS were randomized to receive one of two dose levels, or placebo. Patients receiving cladribine at either dose had annualized relapse rates that were less than half the rate of individuals receiving placebo. They also had a lower risk of sustained progression of disability and a greater reduction in the number of brain lesions identified on MRI relative to the placebo group.
The FDA explains that Mavenclad must be dispensed with a patient Medication Guide, describing important information about the drug’s uses and risks. Mavenclad has a Boxed Warning for an increased risk of malignancy (cancer) and fetal harm. Other warnings include the decreased lymphocyte (white blood cell) counts, infections, liver injury, and other health risks. The most common adverse reactions reported by patients receiving Mavenclad in the clinical trials include upper respiratory tract infections, headache, and decreased lymphocyte counts.
Analysis Shows Number of People with MS to be Much Higher than Previously Estimated
As many as 913,925 people living in the United States had multiple sclerosis (MS) in 2017, according to estimates derived from an extensive analysis of healthcare claims. That number is more than double the previous estimate of 400,000 affected people in the United States.
Researchers arrived at the higher figure by using a sophisticated algorithm (a step-by-step problem-solving process) to analyze the data found in claims from private, public, and military healthcare systems covering more than 125 million people. Investigators estimate between 851,749 people and 913,925 people are living in the United States with MS as of 2017, or from 337.9 to 362.6 cases per 100,000 people.
These findings suggest that there has been a steady rise in the prevalence of MS over the past five decades, the researchers noted. Correcting lower, inaccurate estimates of how many people are affected by MS is critical as the government, payers, and healthcare systems determine how to allocate resources – including research funds and patient-care staff – to address various conditions and diseases.
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.
Portions written by Susan Wells Courtney, MSAA Senior Writer, and Tom Garry, Medical Writer
Reviewed by Dr. Jack Burks, MSAA Chief Medical Consultant