Mayzent® (siponimod) is a once-daily treatment and the first and only oral disease-modifying therapy (DMT) approved in England, Wales and Scotland for adult patients with SPMS with active disease evidenced by relapses or imaging features of inflammatory activity1,2
Until now treatment options for people diagnosed with SPMS with active disease have been very limited3. Siponimod helps to address this unmet need
The NICE and SMC recommendations are based on the Phase III EXPAND study, in which siponimod achieved a sustained effect in delaying disability progression and cognitive decline4,5,6,7,8
London, UK, October 15, 2020 — Novartis today announced that eligible patients in England, Wales and Scotland will soon have access to Mayzent® (siponimod), the first and only oral disease-modifying treatment recommended by both the National Institute for Health and Care Excellence (NICE) and Scottish Medicines Consortium (SMC) licensed to delay disability progression and cognitive decline in secondary progressive multiple sclerosis (SPMS) with active disease4,5,6,7,8. The news comes as the National Institute for Health and Care Excellence (NICE) published the Final Appraisal Document (FAD)* recommending siponimod for the treatment of secondary progressive multiple sclerosis with active disease evidenced by relapses or imaging features of inflammatory activity1,2. The FAD will form the basis of the final guidance that NICE will issue to the NHS in England and Wales. In Scotland, the Scottish Medicines Consortium (SMC) published their final advice on Monday 12th October2.
The diagnosis of SPMS with active disease is often delayed or avoided due to uncertainty around when relapsing remitting multiple sclerosis (RRMS) progresses to SPMS3,9,10. In addition, the very limited treatment landscape, together with these diagnostic challenges, often leads to delay and reluctance in confirming a diagnosis of SPMS3,9,10. 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 disease9,10. Siponimod is the first recommended oral treatment found to be effective in a clinical trial involving patients with SPMS. The approval helps to address this unmet need and offers a licensed treatment option to those patients who have transitioned from RRMS to SPMS with active disease3.
“At the moment there are few options for someone whose MS is changing from relapsing remitting to secondary progressive, so this approval is very welcome and a big step forward,” said David Martin, Chief Executive Officer, Multiple Sclerosis Trust. “By slowing down disability progression and improving cognition, siponimod has the potential to allow people to carry on working, remain independent and stay connected with family and friends. More broadly, we hope that the availability of this new treatment will lead to a greater focus on services for progressive MS which would benefit a much wider group of people.”
Currently it is estimated that SPMS affects 38,000 people in the UK, which is more than a third of all people living with MS11,12,13. Siponimod is the first treatment of its kind to be reviewed by NICE and is the first 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 decline4,5,6,7,8.
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-1914. Siponimod is an oral treatment which patients can take at home and could reduce the worry and stress associated with a journey to hospital.
“The NICE approval of siponimod to treat secondary progressive multiple sclerosis with active disease is a landmark that promises to transform the way we view and manage MS. At last, we have a treatment that can modify the progressive pathology that underpins secondary progressive MS with active disease. The ‘Forgotten Many’ is how people with secondary progressive multiple sclerosis have described themselves; but not anymore,” said Professor Gavin Giovannoni, Professor of Neurology at Barts and the London School of Medicine and Dentistry. “Our challenge is to configure our NHS services to treat patients with secondary progressive MS and to manage expectations, as not all people with secondary progressive multiple sclerosis will be eligible for siponimod. However, this is the beginning of a new era in the management of MS and should be celebrated for that.”
“The decision by both NICE and the SMC represents a significant step forward in ensuring people living with SPMS with active disease in the UK have access to treatment. We are working closely with the NHS to ensure eligible patients can start benefiting from siponimod as soon as possible,” 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.”
About Mayzent (siponimod) Siponimod is a potent and selective small-molecule agonist of sphingosine-1-phosphate (S1P) receptors S1P1 and S1P515,16. Siponimod binds to the S1P1 sub-receptor on lymphocytes, preventing their egress from lymphoid tissues, thereby preventing recirculation to the central nervous system (CNS)17. 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 demyelination17,18,19,20. 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)17. Siponimod was shown to have a safety profile that was overall consistent with the known effects of S1P receptor modulation17. 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)17. 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 placebo4. 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 condition13. 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 loss21. 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)22. There are three types of MS: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)23. 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.
*FAD is subject to factual accuracy check and subject to appeal if requested by stakeholders involved. Following this process which can take up to 3 months, the Technology Appraisal Guidance is formed on the basis of the FAD and represents the formal published guidance from NICE. Clinical commissioning groups, NHS England and, with respect to their public health functions, local authorities, must comply with the NICE TAG that recommends the relevant health service body provides funding within the period specified.
 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.