What was the trial design for the Phase III EXPAND clinical trial?1,2
EXPAND was a randomized, double-blind, parallel-group, placebo-controlled, time-to-event study in 1651 patients with SPMS who had evidence of disability progression in the prior 2 years, no evidence of relapse in 3 months prior to study enrollment, and an EDSS score of 3.0-6.5 at study entry. Patients were randomized 2:1 to receive either once-daily MAYZENT 2 mg or placebo. Evaluations were performed at screening, every 3 months, and when relapses occurred. MRI evaluations were performed at screening and every 12 months. The follow-up duration was 37 months.
The primary end point of the study was the time to 3-month CDP, defined as at least a 1-point increase from baseline in EDSS (0.5-point increase for patients with baseline EDSS of 5.5 or higher) sustained for 3 months. A prespecified hierarchical analysis consisted of the primary end point and 2 key secondary end points, the time to 3-month confirmed worsening by ≥20% from baseline on the T25-FW test, and the change from baseline in T2 lesion volume. Additional end points included ARR (relapses/year) and MRI measures of inflammatory disease activity.
What is the mechanism of action?1,3-8
The dual MOA of MAYZENT targets S1P1,5—2 key receptors thought to play a role in RMS inflammation and neurodegeneration. MAYZENT works in the periphery to limit active lymphocytes from leaving the lymph nodes, which may reduce lymphocyte migration into the CNS. Lipophilic MAYZENT also readily crosses the blood-brain barrier and enters the CNS. MAYZENT binds with high affinity to S1P1,5.
The mechanism by which siponimod exerts therapeutic effects on MS is unknown.
What is the Expanded Disability Status Scale (EDSS)?9
EDSS is a measurement tool that is used to evaluate the progression of physical and/or cognitive disability. EDSS scores range from 0-10 points, and include 0.5-point increments, with higher scores indicating more advanced disability.
What is the indication for MAYZENT?1
MAYZENT is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
What are the most common adverse reactions with MAYZENT?1
The safety profile of MAYZENT was demonstrated in a Phase III clinical trial vs placebo. The most common adverse reactions (incidence ≥10%) were headache (15%), hypertension (13%), and transaminase increases (11%).
How can I get my patients started on MAYZENT?
The MAYZENT Start Form initiates the process in order to get your patient started on MAYZENT. You can fax a hard copy of the Start Form or submit online through your CoverMyMeds account on the Specialty Dashboard tab. E-prescriptions sent through your EMR to Homescripts will automatically push the Start Form to your CoverMyMeds account.
ARR, annualized relapse rate; CDP, confirmed disability progression; CNS, central nervous system; EDSS, Expanded Disability Status Scale; EMR, electronic medical record; MOA, mechanism of action; MOD, mechanism of disease; MRI, magnetic resonance imaging; MS, multiple sclerosis; RMS, relapsing MS; S1P, sphingosine 1-phosphate; T25-FW, timed 25-foot walk.
References: 1. Mayzent [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 2. Kappos L, Bar-Or A, Cree BAC, et al; for the EXPAND Clinical Investigators. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):1263-1273. 3. O’Sullivan C, Schubart A, Mir AK, Dev KK. The dual S1PR1/S1PR5 drug BAF312 (siponimod) attenuates demyelination in organotypic slice cultures. J Neuroinflammation. 2016;13:31. 4. Gergely P, Nuesslein-Hildesheim B, Guerini D, et al. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol. 2012;167(5):1035-1037. 5. Mannioui A, Vauzanges Q, Fini JB, et al. The Xenopus tadpole: an in vivo model to screen drugs favoring remyelination. Mult Scler. 2018;24(11):1421-1432. 6. Choi JW, Chun J. Lysophospholipids and their receptors in the central nervous system. Biochim Biophys Acta. 2013;1831(1):20-32. 7. Briard E, Rudolph B, Desravaud S, Krauser JA, Auberson YP. MS565: a SPECT tracer for evaluating the brain penetration of BAF312 (siponimod). ChemMedChem. 2015;10(6):1008-1018. 8. Behrangi N, Fischbach F, Kipp M. Mechanism of siponimod: anti-inflammatory and neuroprotective mode of action. Cells. 2019;8(24):1-11. 9. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452.