Marketed as Mayzent, the selective sphingosine 1-phosphate receptor modulator is the first treatment for patients with active secondary progressive multiple sclerosis in almost 15 years.
Bruce Bebo, PhD
The FDA has approved siponimod (Mayzent, Novartis) the first treatment for patients with active secondary progressive multiple sclerosis (SPMS) in more than a decade.1
The approval was granted based on data from the EXPAND trial, the largest phase 3 assessment of its kind, including more than 1600 patients with SPMS. It ultimately showed that 3-month confirmed disability progression was reduced by 21% (P
“One of the most important aims of MS treatment is delaying disability progression and preserving cognition,” said Paul Hudson, the chief executive officer of Novartis Pharmaceuticals, in a statement. “With Mayzent, SPMS patients with active disease will have access to the first effective oral therapy directed towards disease progression, even when MS transitions to a stage where deterioration is less dependent on the usual relapse activity.”
“Mayzent is a testament to the Novartis mission to reimagine medicine. We are delighted that our ongoing commitment to stop MS has led to a much-awaited treatment for these patients in need,” he added.
The EXPAND trial additionally showed a 33% reduction in confirmed disability progression compared to placebo in patients with relapse activity in the 24 months prior to screening (P
= .0100). As well, data revealed that the risk of 6-month confirmed disability progression was reduced by 26% compared to placebo (P
= .0058) and that the annualized relapse rate was reduced by 55% with siponimod.
Further, there were significantly favorable outcomes in measurements of disease activity for the siponimod-treated patients, including cognition, magnetic resonance imaging (MRI) lesions, and brain volume loss. All told, the increase in T2 lesion volume was limited by 80% compared to placebo, and more patients were free from gadolinium-enhancing lesions (89%) and from new or enlarging T2 lesions (57%).
The most common adverse reactions (incidence >10%) with siponimod were headache, hypertension, and transaminase increase.
"It’s great to finally have an approved therapy for progressive MS that has a large trial population to support its use in SPMS," Robert J. Fox, MD, a neurologist with Cleveland Clinic's Mellen Center, told NeurologyLive®
. "Before now, we haven’t had a large trial showing efficacy in SPMS, and we haven’t had regulatory approval for SPMS except for a chemotherapy that we don’t use anymore because of its risks and poor efficacy."
"What makes it stand out to me is the large, broad-based trial of SPMS in which it was evaluated. This is a very large and compelling dataset from which to draw our understanding regarding the drug’s efficacy," Fox added.
EXPAND was a double-blind trial that included 1651 participants in 31 countries, who were randomized 2:1 to receive 2 mg of siponimod once daily or placebo. In total, 1099 participants received siponimod and 546 placebo, but of those, 82% (n = 903) and 78% (n = 424) of the siponimod and placebo participants completed the trial, respectively. At the onset of the study, more than 50% of patients relied on a walking aid. Participants were a mean age of 48, with the average time since symptom onset being 16.8 years.
The importance of initiating treatment early in MS is documented in the literature, and as the majority of patients with relapsing disease progress to SPMS, the approval of the selective sphingosine 1-phosphate (S1P) receptor modulator is a welcomed one.3
“We are grateful that there is a new treatment option for adults with active secondary progressive MS,” said Bruce Bebo, PhD, the Executive Vice President of Research at the US National MS Society. “We are hopeful this approval will stimulate a conversation between patients and healthcare professionals about disability progression after relapsing-remitting MS and its early management.”
1. Novartis receives FDA approval for Mayzent® (siponimod), the first oral drug to treat secondary progressive MS with active disease [press release]. Basel, Switzerland: Novartis; Published March 26, 2019. novartis.gcs-web.com/Novartis-receives-FDA-approval-for-Mayzent-siponimod-the-first-oral-drug-to-treat-secondary-progressive-MS-with-active-disease. Accessed March 26, 2019.
2. Kappos L, Cree B, Fox R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomized, phase 3 study. Lancet. Published online March 22, 2018. doi: 10.1016/S0140-6736(18)30475-6.
3. Multiple Sclerosis International Federation. Atlas of MS 2013. msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf.Published 2013. Accessed March 26, 2019.