Novartis reveals landmark multiple sclerosis data showing Gilenya® delivers unprecedented results for children and adolescents
Oct 30, 2017
• PARADIGMS study showed children and adolescents treated with oral Gilenya® (fingolimod) tablets had an 82% lower relapse rate versus injected interferon beta-1a
• Multiple sclerosis (MS) is a highly debilitating disease which can impact every aspect of young patients’ daily lives, from school performance to family relations and friendships
• Novartis is committed to breaking new ground in neuroscience, addressing areas of significant need and improving the lives of those impacted by conditions like MS
Frimley, UK [30 October 2017] – Novartis today announced full results from the positive Phase III PARADIGMS study, investigating the safety and efficacy of Gilenya® (fingolimod) versus interferon beta-1a in children and adolescents (ages 10 to 17) with multiple sclerosis (MS) – a lifelong condition that affects the central nervous system (CNS).3 Results showed that, over a period of up to two years, treatment with Gilenya resulted in an 82% reduction in the rate of relapses compared to interferon beta-1a1 – a current standard of care in the UK. For hundreds of young people in the UK, in whom relapses cause return or worsening of their MS symptoms, Gilenya may offer the first paediatric-specific option able to help improve their quality of life.1 Results were presented at the 7th Joint European and Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) meeting on in Paris, France.
“MS is too-often thought of as a condition that only affects adults, and there remain few licensed treatment options able to help children and adolescents who live with its symptoms on a daily basis,” said Dr Cheryl Hemingway, Consultant Paediatric Neurologist at Great Ormond Street Hospital, London, UK. “The data on Gilenya in this group of patients are some of the most promising we have ever seen. Being able to reduce MS activity by over 80 per cent means these young people could have more time to live their lives free of significant, disabling symptoms. Our hope now is that this will enable us to fundamentally change the course of this disease earlier than ever before.”
PARADIGMS is the first ever controlled, randomised trial exclusively designed for paediatric MS. Currently there are no specifically approved disease modifying therapies for children and adolescents with MS, despite this being a population at high risk of long-term disability.4
Additional data from the study demonstrated:
A significant reduction in the number of new/newly enlarging T2 and Gd-T1 lesions in the brain of Gilenya-treated patients compared to those treated with interferon beta-1a, as measured by magnetic resonance imaging.1 The number and volume of lesions are associated with increased relapses and disability progression.5
Individuals treated with Gilenya had significantly less brain shrinkage (measured by MRI as brain volume loss), compared to those treated with interferon beta-1a.1 Brain shrinkage in adults is associated with the loss of physical and cognitive function.4
The safety profile of Gilenya was overall consistent with that seen in previous clinical trials, with more adverse events reported in the interferon group.1
In an additional analysis, Gilenya significantly delayed disability progression, defined as Confirmed Disability Progression (CDP), compared to interferon beta-1a.1
“Despite there being strong evidence that Gilenya can improve long-term outcomes for adults with relapsing MS, until now it has not been clear if that benefit would translate to young people living with this debilitating condition,” said Dimitrios Georgiopoulos, Chief Scientific Officer at Novartis UK. “Novartis has been leading the fight to find new options for these patients and we are delighted that such meaningful benefits have been seen. Our focus now will be on securing regulatory approval and ensuring that children and teenagers who could benefit from this treatment are able to do so as quickly as possible”.
In 2016 it was estimated that around 107,800 people in the UK were living with MS, with 5,110 new cases diagnosed each year.6 While symptoms often present in adult years, between two and five in every 100 people experience their first MS symptoms before the age of 18.2 Though exact causes of paediatric MS are unknown, high BMI (body mass index) and passive smoking has shown to increase risk.7
Gilenya is not currently approved for the treatment of paediatric MS. Novartis is working on submission with health authorities worldwide.
About the Phase III PARADIGMS study The Phase III PARADIGMS study (NCT01892722) is a flexible duration (up to two years), double-blind, randomised, multi-centre study to evaluate the safety and efficacy of oral Gilenya compared to interferon beta-1a in children and adolescents with a confirmed diagnosis of MS, followed by a five-year open label extension phase . The study enrolled 215 children and adolescents with MS, between the ages of 10 and 17 years with an Expanded Disability Status Scale (EDSS) score between 0 and 5.58. Patients were randomised to receive once-daily oral Gilenya (0.5 mg or 0.25 mg, dependent on patients’ body weight) or intramuscular interferon beta-1a once weekly.8
The primary endpoint of the study was the frequency of relapses in patients treated up to 24 months (annualised relapse rate)8. Secondary endpoints include the number of new or newly enlarged T2 lesions, Gadolinium enhancing T1 lesions, safety and the pharmacokinetic properties of Gilenya, all measured throughout the treatment period8.
The Phase III PARADIGMS study was conducted in 87 sites over 25 countries, and was designed in partnership with the US Food and Drug Administration, the European Medicines Agency and the International Paediatric Multiple Sclerosis Study Group.
UK sites for this study included:
Great Ormond Street Hospital, London
Birmingham Children’s Hospital, Birmingham
Royal Hospital for Sick Children, Edinburgh
About MS 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 loss9. In adults, there are three types of MS: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)10. In children, RRMS accounts for nearly all cases (approximately 98 percent)11.
The evolution of MS results in an increasing loss of both physical and cognitive (e.g. memory) function. This has a substantial negative impact on the lives of the approximately 2.3 million people worldwide affected by MS, of which between three and five percent are estimated to be children.12,13
About Gilenya®q (Gilenya) in adults Gilenya is an oral disease-modifying therapy (DMT) that is highly efficacious at controlling disease activity in relapsing multiple sclerosis (RMS)14. It has a reversible lymphocyte redistribution effect targeting both focal and diffuse CNS damage caused by MS.15,16 Long-term clinical trial and real-world evidence and experience has shown treatment to be convenient for individuals to incorporate into everyday life.17,18
Gilenya impacts four key measures of RMS disease activity: relapses, MRI lesions, brain shrinkage (brain volume loss) and disability progression.19,20 Its effectiveness on all of these measures has been consistently shown in multiple controlled clinical studies and in the real-world setting. Studies have shown its safety and high efficacy to be sustained over the long term, demonstrating that switching to Gilenya treatment as early in the disease course as possible can be beneficial in helping to preserve individuals’ function. 21,22
Gilenya is approved in the EU for adult patients with highly-active relapsing-remitting MS (RRMS) defined as either high disease activity despite treatment with at least one DMT, or rapidly-evolving severe RRMS.23
Gilenya has been used to treat more than 217,000 patients in both clinical trials and the post-marketing setting, with approximately 480,000 years of patient experience.24
About Novartis in MS. Alongside Gilenya (an S1P modulator), Novartis’ MS portfolio includes Extavia® (interferon beta-1b for subcutaneous injection) which is approved in Europe to treat people with relapsing-remitting MS, secondary progressive MS with active disease and people who have had a single clinical event suggestive of MS. In the US, the Sandoz Division of Novartis markets Glatopa® (glatiramer acetate injection) 20mg/mL, the first generic version of Teva's Copaxone®* 20mg.
*Copaxone® is a registered trademark of Teva Pharmaceutical Industries Ltd.
About Novartis Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2015, the Group achieved net sales of USD 49.4 billion, while R&D throughout the Group amounted to approximately USD 8.9 billion (USD 8.7 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, please visit www.novartis.com.
In the UK, Novartis develops, manufactures and markets innovative medicines, devices and diagnostic tests which help improve patient outcomes. Based on four sites across the north and south of England, 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 by manufacturing the active pharmaceutical ingredients used worldwide in many medicines. In 2015 Novartis in the UK invested over £50million in R&D and is the largest commercial sponsor of clinical trials. For more information, please visit www.novartis.co.uk.
1 Chitnis T et al. PARADIGMS: A Randomised Double-blind Study of Fingolimod Versus Interferon β-1a in Paediatric Multiple Sclerosis. Late breaking news oral presentation presented at: the 7th Joint ECTRIMS-ACTRIMS meeting on October 28, 2017, Paris, France. 2 https://www.mstrust.org.uk/a-z/childhood-ms (link is external). Accessed October 2017. 3 https://www.mstrust.org.uk/what-ms?gclid=EAIaIQobChMIiZfXxcmL1wIVYxbTCh0PdwOJEAAYAiAAEgIyCfD_BwE (link is external). Accessed October 2017. 4 Popescu Vet al; on behalf of the MAGNIMS Study Group. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013;84:1082-1091. 5 Sormani MP and Bruzzi P. MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomized trials. Lancet Neurol. 2013;12(7):669-76. 6 https://www.mssociety.org.uk/sites/default/files/MS%20in%20the%20UK%20January%202016_0.pdf 7 https://www.mssociety.org.uk/causes-ms (link is external). Accessed October 2017. 8 Clinical Trials. Safety and efficacy of fingolimod in pediatric patients with multiple sclerosis. https://clinicaltrials.gov/ct2/show/NCT01892722 (link is external). Accessed October 2017. 9 PubMed Heath. Multiple Sclerosis (MS). http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001747/ (link is external). Accessed October 2017. 10 MS Society. Types of MS. https://www.mssociety.org.uk/what-is-ms/types-of-ms (link is external). Accessed October 2017. 11 Waldman A et al. Pediatric multiple sclerosis. Neurology. 2016;87(9):S74-S81. 12 Patel Y et al. Pediatric multiple sclerosis. Ann Indian Acad Neurol. 2009;12(4):238-245. 13 Multiple sclerosis international federation. Atlas of MS 2013. https://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf (link is external). Accessed October 2017. 14 Gilenya US Prescribing Information. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/gilenya.pdf (link is external). Accessed October 2017. 15 Brinkmann V et al. FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol. 2009;158(5):1173-1182. 16 De Stefano N et al. Effect of fingolimod on diffuse brain tissue damage in relapsing-remitting multiple sclerosis patients. Mult Scler Relat Disord. 2016;7:98-101. 17 Warrender-Sparkes M et al. The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis. Mult Scler. 2016;22(4):520-532. 18 Khatri B et al. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol. 2011;10(6):520-529. 19 Giovannoni G et al. "No evident disease activity": The use of combined assessments in the management of patients with multiple sclerosis. Mult Scler. 2017. Doi 10.1177/1352458517703193. 20 De Stefano N et al. Effect of Fingolimod on Brain Volume Loss in Patients with Multiple Sclerosis. CNS Drugs. 2017;31(4):289-305. 21 Kappos L et al. Inclusion of brain volume loss in a revised measure of 'no evidence of disease activity' (NEDA-4) in relapsing-remitting multiple sclerosis. Mult Scler. 2016;22(10):1297-1305. 22 Lizac N et al. Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(3):196-203. 23 Gilenya EMA Summary of Product Characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002202/WC500104528.pdf (link is external). Accessed October 2017. 24 Novartis data on file.