Novartis response to NICE Appraisal Consultation Document (ACD) for Mayzent®▼ (siponimod) for the treatment of secondary progressive multiple sclerosis with active disease

We at Novartis UK are disappointed by the initial decision from the National Institute for Health and Care Excellence (NICE) not to recommend Mayzent^® (siponimod) for the treatment of secondary progressive multiple sclerosis (SPMS) with active disease, for routine use on the NHS. Currently, treatment options for people diagnosed with SPMS with active disease are extremely limited and we believe siponimod addresses an unmet need in this patient population.

The diagnosis of SPMS with active disease is often delayed or avoided due to uncertainty around when relapsing remitting MS (RRMS) progresses to SPMS1,2,3. The very limited treatment landscape, together with these diagnostic challenges, often leads to delay and reluctance in confirming a diagnosis of SPMS with active disease^1,2,3. 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 disease^2,3.

Whilst the NICE committee acknowledged the clinical effectiveness of siponimod, which has a sustained effect in delaying disability progression^4,5,6 , they concluded that RRMS treatments were not relevant comparators for cost-effectiveness analysis. We believe that the comparator should reflect NHS practice and that since many patients with SPMS continue to receive treatment for RRMS^2,3, RRMS treatments are the more appropriate comparators for this appraisal. Demonstrating cost-effectiveness versus no treatment (i.e. best supportive care) is challenging, so this approach could risk patients being left unable to access truly innovative medicines such as siponimod.

Treatment with siponimod has also been shown to have a significant benefit on cognitive processing speed, the cognitive function most frequently affected by MS^5,6^,7,8. Cognitive changes, including problems with memory, attention span, decision making, and understanding, can significantly impact quality of life and are a key concern for people living with MS^9,10.

If the initial decision from NICE remains unchanged patients will be denied access to the first licensed oral therapy for SPMS with active disease, leaving them without an effective, convenient treatment to manage their condition and help them maintain independence for longer.

We are committed to continuing to work closely with NICE to address outstanding questions and data requirements in order to secure access as quickly as possible to siponimod for those patients in England and Wales that could benefit.

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NOTES TO EDITORS

• This guidance is draft and open for consultation until 16 July 2020 during which time anyone wishing to comment can do so on the NICE website: www.nice.org.uk/guidance/indevelopment/gid-ta10436.
• SPMS is characterised by a progressive accumulation of disability over time and an increasing loss of both physical and cognitive functions, including mobility issues, numbness, and problems with thinking, learning and planning^11,12. While the rate of MS progression is different for each person and influenced by multiple factors, including the use of MS disease-modifying therapies (DMTs), studies have shown that between 24% and 40% of people with relapsing remitting MS (RRMS) progress to SPMS within 10 years from diagnosis^13,14,15.
• People living with SPMS with active disease experience relapses or new inflammatory activity, demonstrated by changes on MRI scans¹¹.

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References

[1] MS Trust. Secondary progressive multiple sclerosis. Available at: https://support.mstrust.org.uk/file/SPMS-A5-Booklet-Oct-2018-FINAL-WEB.pdf. Accessed June 2020.

2 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.

3 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.

4 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.

⁵ 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).

6 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 35^th 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.

7 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.

8 Chiaravalloti N, DeLuca J. Cognitive impairment in multiple sclerosis. The Lancet Neurology. 2008;7(12):1139-1151.

9 MS Trust. Thinking and memory problems. Available at: https://www.mstrust.org.uk/life-ms/wellbeing/thinking-and-memory-problems. Accessed June 2020.

10 MS International Federation. Emotional and cognitive changes. Available at: https://www.msif.org/about-ms/symptoms-of-ms/cognition-and-emotional-changes/. Accessed June 2020.

11 National Multiple Sclerosis Society. Secondary Progressive MS (SPMS). https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Secondary-progressive-MS. Accessed March 2020.

12 NHS. Multiple sclerosis – Symptoms. Available at: https://www.nhs.uk/conditions/multiple-sclerosis/symptoms/. Accessed June 2020.

13 Tremlett H, Yinshan Z, Devonshire V. Natural history of secondary-progressive multiple sclerosis. Mult Scler. 2008; 14: 314-324.

14 Scalfari A, Neuhaus A, Daumer M, Muraro PA, Ebers GC. Onset of secondary progressive phase and long-term evolution of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014; 85: 67-75.

15 Rovaris M, Confavreux C, Furlan R, Kappos L, Comi G, Filippi M. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol. 2006; 5: 343-354.