Novartis data at AAN show positive effect of siponimod on cognition in secondary progressive MS

Frimley, UK, May 8, 2019 – Novartis today announced a new subgroup analysis of the Phase III EXPAND study of oral, once-daily siponimod (BAF312) in patients with secondary progressive multiple sclerosis (SPMS). The results show siponimod, the first and only oral drug to delay disability progression in SPMS patients, has significant functional benefit on cognitive processing speed (CPS), the cognitive function most frequently affected by MS^i,ii,[iv].

The new findings, presented at the 2019 American Academy of Neurology Annual Meeting (AAN) in Philadelphia, Pennsylvania, USA, show that patients treated earlier in their disease course with less cognitive impairment benefited most from siponimod treatment vs. placeboⁱ. This suggests that earlier treatment can lead to better cognitive outcomes, reinforcing the potential of siponimod in addressing a high unmet need for effective treatment of SPMS.

Cognitive changes, including problems with memory, attention span, decision making, and understanding, can significantly impact quality of life, affecting a person’s ability to work and fulfil day-to-day responsibilities^[v],[vi]. Up to 70% of people living with MS will experience cognitive impairment, which is more severe in patients with SPMS than relapsing remitting MS (RRMS)^ii,iii.

“Cognitive decline is a key concern for people living with MS, and the value of being able to slow deterioration cannot be underestimated,” said Dr Matthew Craner, Consultant Neurologist at University of Oxford. “Building on previous EXPAND results, the results of this subgroup analysis support the need for early diagnosis and management of SPMS to help improve cognitive outcomes for people living with MS.”

It is estimated that there are over 100,000 people living with MS in the UK, of which approximately 85% have been diagnosed with RRMS^[vii],[viii]. Studies have shown that between 24% and 40% of people with RRMS progress to SPMS within 10 years from diagnosis^{[ix],[x],[xi]}. SPMS leads to progressive, irreversible disability, and once diagnosed can impact the condition management options available to patients^[xii]. There are currently no licensed oral disease modifying therapies available for the estimated 38,000 people in the UK living with SPMS^{xii,[xiii],[xiv]}.

“At Novartis, we are committed to delivering groundbreaking innovations that have the potential to redefine what it means to live with complex and debilitating conditions such as SPMS," said Dr Mark Toms, Chief Scientific Officer, Novartis UK. “The significant positive effects of siponimod on cognition further demonstrate the impact it could bring, and we will continue working closely with regulatory bodies to make sure this new treatment is made available for those who it could benefit.”

In EXPAND, CPS was measured using the Symbol Digit Modalities Test (SDMT), the recommended gold standard measure of CPS in MS clinical studies^i,[xv]. The results demonstrated a significantly greater proportion of patients treated with siponimod experienced a sustained SDMT improvement than those receiving placebo, whether or not patients showed cognitive impairment at baselineⁱ.

The marketing authorisation application for siponimod is currently under review by the EMA, with decisions anticipated in Q4 2019. Siponimod was FDA approved for the treatment of adults with relapsing forms of multiple sclerosis, including SPMS with active disease, RRMS and clinically isolated syndrome (CIS) in March 2019.

[iv] 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.

[v] MS Trust. Thinking and memory problems. Available at: https://www.mstrust.org.uk/life-ms/wellbeing/thinking-and-memory-problems. Accessed April 2019.

[vi] MS International Federation. Emotional and cognitive changes. Available at: https://www.msif.org/about-ms/symptoms-of-ms/cognition-and-emotional-changes/. Accessed April 2019.

[vii] 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 2019.

[viii] Multiple Sclerosis International Federation. Atlas of MS 2013. Available at: http://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf. Accessed April 2019.

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

[x] 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.

[xi] 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.

[xii] MS Trust. Secondary Progressive Multiple Sclerosis. Available at: https://support.mstrust.org.uk/file/SPMS-A5-Booklet-Oct-2018-FINAL-WEB.pdf. Accessed April 2019.

[xiii] 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).

[xiv] Office of National Statistics. Population mid-year estimates, 2017. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/timeseries/ukpop/pop. Accessed April 2019.

[xv] Benedict R, DeLuca J, Phillips G, LaRocca N, Hudson L, Rudick R. Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis. Multiple Sclerosis Journal. 2017;23(5):721-733.