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As was the case for siponimod’s FDA approval in March 2019, this regulatory decision by the European Commission for the selective sphingosine-1-phosphate receptor modulator was based on the phase 3 EXPAND trial.
Pedro Carrascal, MBA
Novartis has announced that its selective sphingosine-1-phosphate (S1P) receptor modulator, siponimod (Mayzent) has been approved for use in Europe for the treatment for patients with active secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.1
As was the case for its FDA approval in March 2019, this regulatory decision by the European Commission was based on the phase 3 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 = .013).2
“We are delighted by the news that there is now a treatment available for people in Europe living with active SPMS to potentially delay the progression of this debilitating disease,” said Pedro Carrascal, MBA, president, European MS Platform, in a statement. “This treatment brings hope for improved care and quality of life to patients who have long been underserved.”
EXPAND, notably, included a subgroup with active disease (n = 779)—defined as relapse within ≤2 years prior to the study and/or presence of gadolinium-enhancing T1 lesions—with baseline characteristics otherwise similar to the overall population. In that subgroup, the risk of 3‑ and 6‑month confirmed disability progression was reduced by 31% and 37% compared to placebo, respectively.
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.
“As the only indicated oral therapy proven for people living with SPMS with active disease, we are pleased that the European approval of Mayzent will help change the conversation about progressing MS and expand possibilities for patients and their caregivers,” Max Bricchi, MBA, Global Head, Neuroscience, Novartis, said in a statement. “Delaying progression is hugely important for people living with MS who want to maintain independence longer and today’s decision gives them a chance to achieve this goal.”
Furthermore, significantly favorable outcomes were observed in measurements of disease activity for the siponimod group, including cognition, magnetic resonance imaging (MRI) lesions, and brain volume loss. In total, T2 lesion volume increase 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 events (AEs), occurring in >10% of patients 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 at the time of its approval in the US. "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."
1. Novartis announces EU approval of Mayzent® (siponimod) for adult patients with secondary progressive multiple sclerosis (SPMS) with active disease [press release]. Basel, Switzerland: Novartis; Published January 20, 2020. finance.yahoo.com/news/novartis-announces-eu-approval-mayzent-143207483.html. Accessed January 20, 2020.
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.