Novartis’ Mayzent®▼ (siponimod) receives approval from the Scottish Medicines Consortium as the first recommended treatment in Scotland for patients living with secondary progressive multiple sclerosis (SPMS) with active disease
Mayzent® (siponimod) is a once-daily treatment and the first recommended and only oral disease-modifying therapy (DMT) approved by the Scottish Medicines Consortium (SMC) for adult patients with SPMS with active disease evidenced by relapses or imaging features of inflammatory activity1
Until now treatment options for people diagnosed with SPMS with active disease have been very limited2. Siponimod helps to address this unmet need
The SMC advice is based on the Phase III EXPAND study, in which siponimod achieved a sustained effect in delaying disability progression and cognitive decline3,4,5,6,7
London, UK, October 12, 2020 — Novartis today announced that eligible patients in Scotland will soon have access to Mayzent® (siponimod), the first recommended and only oral disease-modifying therapy licensed to delay disability progression in secondary progressive multiple sclerosis (SPMS) with active disease3,4,5,6,7. The news comes as the Scottish Medicines Consortium (SMC) published their final advice recommending siponimod for the treatment of secondary progressive multiple sclerosis with active disease evidenced by relapses or imaging features of inflammatory activity in adults1.
The diagnosis of SPMS with active disease is often delayed or avoided due to uncertainty around when relapsing remitting multiple sclerosis (RRMS) progresses to SPMS2,8,9. In addition, the very limited treatment landscape, together with these diagnostic challenges, often leads to delay and reluctance in confirming a diagnosis of SPMS 2,8,9. As a result, it is likely that many people with SPMS with active disease continue to receive treatment licensed for use in RRMS, which has not been proven effective for treating their disease8,9. Siponimod is the first oral treatment found to be effective in a clinical trial involving patients with SPMS. This positive decision from the SMC helps to address an unmet need by providing a licensed treatment option to Scottish patients who have transitioned from RRMS to SPMS with active disease2.
“For a long time people with SPMS and their families have managed not only living with a challenging disease, but also knowing that there’s very little their healthcare team can do to slow the course of this progressive stage of MS”, said Iain Morrison, Chief Executive, Revive MS Support. “The news that siponimod will now be made available to people living with SPMS with active disease in Scotland will be a ray of hope for many people living with, and caring for people living with SPMS with active disease.”
Currently over 15,000 people live with MS in Scotland with approximately a third of these developing SPMS10,11. This makes MS more common in Scotland than many other countries in the world11,12,13,14. Siponimod is the first treatment of its kind to be reviewed by SMC and is the first recommended and only oral disease modifying therapy for people living with SPMS with active disease that is proven to have a sustained effect in delaying disability progression and cognitive decline3,4,5,6,7.
A recent survey of the general public found that over half of those surveyed felt worried about going into hospital for their appointments in light of COVID-19.15 Siponimod is an oral treatment which patients can take at home and could reduce the worry and stress associated with a journey to hospital.
“Siponimod has been shown to delay disability progression and cognitive decline, which could help people with SPMS with active disease stay independent for longer”, said Dr Francisco Javier Carod Artal, Consultant Neurologist, Raigmore hospital, NHS Highlands. “Despite wanting to do their best for their patients, clinicians have been very limited in the treatments they could offer this group of people living with MS. The decision by the SMC to recommend siponimod means that people living with SPMS with active disease now have access to a treatment that may provide relief from MS symptoms and offer hope for a more manageable future”.
“The decision from the SMC represents a significant step forward in ensuring people living with SPMS with active disease in Scotland have access to appropriate treatment. We are working closely with NHS Scotland to ensure eligible patients can start benefiting from siponimod as soon as possible and we continue to work with NICE as part of their review process in the hope that people living with SPMS with active disease in other parts of the UK will also have access soon,” said Chinmay Bhatt, Managing Director UK, Ireland & Nordics for Novartis Pharmaceuticals. “We are proud to build on our heritage in neuroscience and our ongoing commitment to reimagining medicine for people living with MS.”
Novartis is expecting a decision from the National Institute for Health and Care Excellence (NICE) later this month.
About Mayzent (siponimod) Siponimod is a potent and selective small-molecule agonist of sphingosine-1-phosphate (S1P) receptors S1P1 and S1P5,16,17. Siponimod binds to the S1P1 sub-receptor on lymphocytes, preventing their egress from lymphoid tissues, thereby preventing recirculation to the central nervous system (CNS)18. Siponimod readily crosses the blood-brain barrier, and findings from pre-clinical studies suggest that siponimod prevents synaptic neurodegeneration, has the potential to promote remyelination in the CNS, and modulates pathways involved in cell survival with subsequent reduction of demyelination18,19,20,21. The implications of these pre-clinical findings on the clinical mechanism of action are unclear.
Siponimod has been studied in the Phase III EXPAND study, a randomised, double-blind, placebo-controlled trial comparing the efficacy and safety of siponimod versus placebo in in 1,651 people with SPMS with varying levels of disability (Expanded Disability Status Scale [EDSS] scores of 3.0 to 6.5)18. Siponimod was shown to have a safety profile that was overall consistent with the known effects of S1P receptor modulation18. Results showed that siponimod reduced the risk of three-month confirmed disability progression (CDP) by a statistically significant 21% versus placebo (26% of patients in siponimod group vs 32% in placebo group had 3-month CDP; hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.65–0.95; p=0.013; primary endpoint)18. Specifically, in the post hoc analysis of the SPMS with active disease subgroup (n=779), results demonstrated that siponimod reduced the risk of three- and six-month CDP by 31% (HR 0.69, 95% CI 0.53–0.91; p=0.0094) and 37% (HR 0.63, 95% CI 0.47–0.86, p=0.0040) respectively versus placebo3. CDP was defined as a 1-point increase in EDSS if the baseline score was 3.0 to 5.0, or a 0.5-point increase if the baseline score was 5.5 to 6.5.
About Multiple Sclerosis
There are approximately 130,000 people with multiple sclerosis (MS) in the UK, and each year around 7,000 people are newly diagnosed with the condition14. MS is a chronic disorder of the central nervous system (CNS) that disrupts the normal functioning of the brain, optic nerves and spinal cord through inflammation and tissue loss22. The evolution of MS results in an increasing loss of both physical and cognitive functions (e.g. mobility problems, numbness, bladder and bowel problems, and problems with thinking, learning and planning)23. There are three types of MS: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)10. Patients with relapsing forms of MS – including RRMS and SPMS with active disease – experience distinct attacks of symptoms, known as relapses24,25. Around 85% of people are considered to have RRMS at their point of diagnosis26. SPMS, which typically follows from an initial RRMS course, is characterised by a gradual worsening of neurological function over time, and can be described as active (with relapses and/or evidence of new MRI activity) or not active (no evidence of current activity)24,27.
About Novartis in Multiple Sclerosis
Novartis has a strong ongoing commitment to neuroscience and to bringing innovative treatments to patients suffering from neurological conditions where there is a high unmet need. The Novartis multiple sclerosis (MS) portfolio includes Gilenya®▼ (fingolimod, an S1P modulator), which is licenced in Europe for the treatment of adults and children aged 10 and older with highly active RRMS. Mayzent®▼ (siponimod) is licenced in Europe for the treatment of adult patients with SPMS with active disease evidenced by relapses or imaging features of inflammatory activity. Extavia® (interferon beta-1b for subcutaneous injection) is approved in Europe to treat people with RRMS (>2 relapses in the last 24 months), people with SPMS with active disease (evidenced by relapses), and people who have had a single clinical event suggestive of MS with an active inflammatory process.
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach more than 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 130,000 people of nearly 150 nationalities work at Novartis around the world. Find out more at www.novartis.com.
In the UK, we employ approximately 1,500 people to serve healthcare needs across the whole of the UK, as well as supporting the global operations of Novartis. Since 2014, Novartis has invested over £200 million in R&D and is a leading sponsor of clinical trials, in the UK. For more information, please visit www.novartis.co.uk.
 Gold R, Kappos L, Bar-Or A, et al. Efficacy of Siponimod in Secondary Progressive Multiple Sclerosis Patients With Active Disease: The EXPAND Study Subgroup Analysis. Poster presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis and 24th Annual Conference of Rehabilitation in MS, 11–13 September 2019, Stockholm, Sweden
 Kappos L, et al. Long-term Efficacy and Safety of Siponimod in Patients with SPMS: EXPAND Extension Analysis up to 5 Years. Neurology. 2020; 94 (15 Supplement).
 Benedict R, Fox R, Tomic D, et al. Effect of Siponimod on Cognition in Patients with Secondary Progressive Multiple Sclerosis (SPMS): Phase 3 EXPAND Study Subgroup Analysis. Poster presentation. 2019 American Academy of Neurology Annual Meeting, May 7, 2019
 Giovannoni. G et.al. Sustained reduction of disability and cognitive decline with long-term siponimod treatment in patients with active SPMS: EXPAND data up to 5 years. ECTRIMS 2020 ePosterP0238.
 Penner. I. K et.al. Effect of siponimod on cognitive processing speed in SPMS patients with active and non-active disease. ECTRIMS 2020 ePoster P0806.
 Duddy M, Wilkinson C, Rhys K. Diagnosis of Secondary Progressive Multiple Sclerosis in UK Centres: Results from the SPECTRUM project. Poster presented at the MS Trust Annual Conference, 3-5 November 2019.
 Caseby SCL, Montgomery SM, Woodhouse FA, Kroes MA. Transition to secondary progressive multiple sclerosis: When is SPMS identified in the UK and what are the consequences for patients and the National Health Service? Poster presented at the MS Trust Conference, 3−5 November 2019.
 Khurana V, Sharma H, Medin J. Estimated prevalence of secondary progressive multiple sclerosis in the USA and Europe: results from a systematic literature search. 2018; Neurology 90: (15 supplement).
 Gergely P, 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):1035-47.
 Pan S, Gray NS, Gao W, et al. Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator. ACS Med Chem Lett 2013;4:333-7.
 Kappos L, Cree B, Fox R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. The Lancet. 2018;391(10127):1263-1273.
 Gentile A, Musella A, Bullitta S, et al. Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis. J Neuroinflammation 2016; 13: 207.
 Martin E, Urban B, Beerli C, et al. Siponimod (BAF312) is a Potent Promyelinating Agent: Preclinical Mechanistic Observations. Poster presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, September 2019.
 O'Sullivan C, Schubart A, Mir AK, et al. The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures. J Neuroinflammation 2016;13:31.