Novartis announces new Mayzent®▼(siponimod) data showing sustained effect in delaying disability progression for up to five years in patients with secondary progressive multiple sclerosis

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Apr 21, 2020
  • New long-term data from the extension part of the EXPAND study shows that patients with secondary progressive multiple sclerosis (SPMS) continuously treated with siponimod experienced a lower risk of disability progression and cognitive decline than patients who delayed siponimod treatment[i]
  • Separate post-hoc analyses from EXPAND demonstrated siponimod reduced cortical grey matter (cGM) atrophy and thalamic atrophy in patients with SPMS[ii], outcomes associated with long-term irreversible disability accumulation[iii]
  • Mayzent is licensed in the UK for the treatment of adult patients with secondary progressive multiple sclerosis with active disease evidenced by relapses or imaging features of inflammatory activity[iv]

London, UK, April 21, 2020 – Novartis today announced new Mayzent® (siponimod) data which demonstrate the long-term efficacy of siponimod in lowering the risk of disability progression and cognitive decline. The data is published in the April supplemental issue of Neurology®, the medical journal of the American Academy of Neurology, and builds on existing clinical evidence that siponimod has a significant positive effect on the physical and cognitive abilities of patients living with secondary progressive multiple sclerosis (SPMS)1. Siponimod is licensed for the treatment of adult patients with secondary progressive multiple sclerosis with active disease evidenced by relapses or imaging features of inflammatory activity4.

Data released from the core and extension parts of the EXPAND trial (total duration ≤ 5 years, 1,224 participants in the trial extension) assessed the efficacy and safety of siponimod in patients with SPMS who, on entering the extension trial, either continued on siponimod treatment (siponimod group) or switched to siponimod from placebo (placebo switch group). Patients in the siponimod group were significantly less likely to experience both three- and six-month confirmed disability progression (CDP), p=0.0064 and p=0.0048, respectively) compared with the placebo switch group1. This data was included in the April supplemental issue of Neurology after the 2020 American Academy of Neurology Annual Meeting was cancelled due to COVID-19.

 

“These data highlight the critical importance of early treatment intervention with a disease-modifying treatment, such as Mayzent, to ensure the best possible long-term outcomes for patients with MS who are experiencing progression,” said Bruce Cree, MD, PhD, MAS, Clinical Research Director and George A. Zimmermann Endowed Professor in Multiple Sclerosis, University of California, San Francisco, School of Medicine. “It’s never too early to stay ahead of progression in multiple sclerosis, since the early identification of physical and cognitive changes – even subtle ones – can indicate MS disease progression and therefore allow for timely intervention.”

 

The new data also showed a 52% reduction in the annualised relapse rate (ARR) observed in the siponimod group compared to the placebo group (p<0.0001). Risk of confirmed worsening of cognitive impairment (according to the Symbol Digit Modalities Test) at six-months was reduced by 23% for the siponimod group  compared with the placebo (p=0.0014). The benefits seen in the siponimod group were sustained for up to five years, underlining the advantages of early treatment initiation with siponimod. The incidence of adverse events was consistent with the controlled treatment period1. This EXPAND open-label extension is ongoing for up to a total of seven years.

 

Additional siponimod data shared in the same Neurology issue includes a new post-hoc analysis from EXPAND, which showed siponimod consistently reduced cortical grey matter (cGM) and thalamic atrophy in patients with SPMS, including those with less active and more advanced disease. Across the subgroups studied, siponimod reduced cGM atrophy versus placebo by 48–116% (p<0.01 at both M12 and M24) and thalamic atrophy by 30% to 68% (p<0.05 at both M12 and M24; except for ‘disease duration >15 years’ p=0.1029 at M12)2. Combined with other analyses, these findings could translate into a favourable impact on long-term clinical outcomes including disability progression and cognitive decline.

 

“These data demonstrate that early and continued treatment with siponimod can support people living with SPMS by delaying their disability progression and cognitive decline, helping them to maintain their independence for longer,” said Dr Mark Toms, Chief Scientific Officer, Novartis UK. “Novartis continues to work to improve the lives of patients with debilitating neurological conditions by delivering new medicines, and with siponimod, Novartis offers patients with SPMS with active disease hope for improved health outcomes.”

 

About Mayzent (siponimod)
Siponimod is a potent and selective small-molecule agonist of sphingosine-1-phosphate (S1P) receptors S1P1 and S1P5[v],[vi]. Siponimod binds to the S1P1 sub-receptor on lymphocytes, preventing their egress from lymphoid tissues, thereby preventing recirculation to the central nervous system (CNS)[vii]. 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 demyelination7,[viii],[ix],[x].

 

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)7. Siponimod was shown to have a safety profile that was overall consistent with the known effects of S1P receptor modulation7. 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)7. 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 placebo[xi]. 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 110,000 people with multiple sclerosis (MS) in the UK, and each year around 5,000 people are newly diagnosed with the condition[xii],[xiii]. 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 loss[xiv]. 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)[xv]. There are three types of MS: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)[xvi].

 

SPMS is characterised by gradual worsening of neurological function over time[xvii]. This leads to a progressive accumulation of disability, which can severely affect patients’ ability to carry out everyday activities17. SPMS can be active (with relapses or evidence of new MRI activity) or non-active17. There remains a high unmet need for effective treatments to help delay disability progression in SPMS[xviii].

 

About Novartis in Multiple Sclerosis 
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 relapsing remitting forms of MS. Extavia® (interferon beta-1b for subcutaneous injection) is approved in Europe to treat people with RRMS, people with SPMS with active disease (evidenced by relapses), and people who have had a single clinical event suggestive of MS.

 

About Novartis

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

 

Novartis UK is on Twitter. Sign up to follow @NovartisUK at www.twitter.com/novartisuk

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Novartis UK Media Relations

Novartis UK Press Office

Tel: 07771 541379 / 01276 698 691

E-Mail: [email protected]

 

April 2020 | MAY20-E001

[i] 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).

[ii] Fox R, et al. Siponimod Reduces Grey Matter Atrophy in Patients with Secondary Progressive Multiple Sclerosis: Subgroup Analyses from the EXPAND study. Neurology. 2020; 94 (15 Supplement).

[iii]Arnold DL, et al. Relationship between grey matter atrophy, disability and cognition in patients with secondary progressive multiple sclerosis: analysis from the EXPAND study. 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), September 2019.

[iv]European Medicines Agency (EMA). Mayzent – Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/mayzent-epar-.... Accessed April 2020. 

[v] 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.

[vi]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.

[vii] 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.

[viii] Gentile A, Musella A, Bullitta S, et al. Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis. J Neuroinflammation 2016; 13: 207.

[ix] 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.

[x] 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.

[xi] 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.

[xii] MS Trust. Prevalence and incidence of multiple sclerosis. Available at: https://www.mstrust.org.uk/a-z/prevalence-and-incidence-multiple-sclerosis. Accessed April 2020.

[xiii] MS Society. MS in the UK. Available at: https://www.mssociety.org.uk/what-we-do/our-work/our-evidence/ms-in-the-uk. Accessed April 2020.

[xiv] American Association of Neurological Surgeons. Multiple Sclerosis. Available at: https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Multiple-Sclerosis. Accessed April 2020.

[xv] NHS. Multiple sclerosis – Symptoms. Available at: https://www.nhs.uk/conditions/multiple-sclerosis/symptoms/. Accessed April 2020.

[xvi] MS Society. Types of MS. Available at: https://www.mssociety.org.uk/what-is-ms/types-of-ms. Accessed April 2020.

[xvii] National Multiple Sclerosis Society. Secondary Progressive MS (SPMS). https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Secondary-progr.... Accessed April 2020.

[xviii] Mehr S.R. and Zimmerman M.P. Reviewing the unmet needs of patients with multiple sclerosis. Am Health Drug Benefits. 2015; 8(6);426-431.