The U.S. Food and Drug Administration today approved Mayzent (siponimod) tablets by Novartis to treat adults with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communications between the brain and other parts of the body. Most people experience their first symptoms of MS between the ages of 20 and 40. MS is among the most common causes of neurological disability in young adults and occurs more frequently in women than in men.
For most people, MS starts with a relapsing-remitting course, in which episodes of worsening function (relapses) are followed by recovery periods (remissions). These remissions may not be complete and may leave patients with some degree of residual disability. Many patients with MS experience some degree of persistent disability that gradually worsens over time. In some patients, disability may progress independent of relapses, a process termed secondary progressive multiple sclerosis (SPMS). In the first few years of this process, many patients continue to experience relapses, a phase of the disease described as active SPMS. Active SPMS is one of the relapsing forms of MS, and drugs approved for the treatment of relapsing forms of MS can be used to treat active SPMS. Later, many patients with SPMS stop experiencing new relapses, but disability continues to progress, a phase called non-active SPMS.
Mayzent is the first drug approved for patients with active secondary progressive multiple sclerosis (SPMS) in over 15 years and the first oral formulation. Mayzent is the first second-generation sphingosine 1-phosphate (S1P) receptor modulator to enter the MS market and has the same mechanism of action as Gilenya, which generated $3.34bn in 2018. Mayzent is more receptor-specific than Gilenya, which improves efficacy and reduces cardiac side effects, so the company expects Mayzent to generate $1.79 billion in sales by 2026 in the big seven countries - US, France, Germany, Italy, Spain, UK, and Japan.
Approval was granted based on data from the Phase III EXPAND trial, with results showing that Mayzent significantly reduced the risk of three-month confirmed disability progression in patients with active disease by 21%, compared with placebo. The drug also reduced the annualized relapse rate by 55%.
The latest clinical trial was of 1,651 patients that compared Mayzent to placebo in patients with SPMS who had evidence of disability progression in the prior two years and no relapses in the three months prior to enrollment. The primary endpoint of the study was the time to three-month confirmed progression in disability. The fraction of patients with confirmed progression of disability was statistically significantly lower in the Mayzent group than in the placebo group. Mayzent also decreased the number of relapses experienced by these patients. In the subgroup of patients with non-active SPMS, the results were not statistically significant.
The most common adverse reactions reported by patients receiving Mayzent in the clinical trials include headache, high blood pressure and liver function test increases.