Novartis has announced full results from the positive phase III PARADIGMS study, investigating the safety and efficacy of Gilenya (fingolimod) vs. interferon beta-1a, in children and adolescents (ages 10 to 17) with multiple sclerosis (MS).
Treatment with oral Gilenya resulted in an 82% reduction in the rate of relapses (annualized relapse rate) over a period of up to two years, compared to interferon beta-1a intramuscular injections (p <0.001). PARADIGMS is the first ever controlled, randomized trial specifically designed for pediatric MS. The results have been presented at the 7th Joint European and Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) meeting on October 28, 2017 in Paris, France.
“Pediatric MS patients experience more frequent relapses and are more likely to accumulate physical disability at an earlier age than patients diagnosed as adults,” said Dr. Tanuja Chitnis, principle investigator for PARADIGMS and director of the Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital, Boston, US, and Scientist, Ann Romney Center, Brigham and Women’s Hospital, Boston, US. “Yet, current therapies are limited to drugs that have not been tested in a controlled manner in this age group. PARADIGMS was uniquely designed for this patient population. Its results signify an important step towards a potential new treatment that could improve the lives of these young patients.”
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 (MRI). The number and volume of lesions are associated with increased relapses and disability progression. Individuals treated with Gilenya had significantly less brain shrinkage (measured by MRI as brain volume loss), compared to those treated with interferon beta-1a. Brain shrinkage in adults is associated with the loss of physical and cognitive function. The safety profile of Gilenya was overall consistent with that seen in previous clinical trials, with more adverse events reported in the interferon group. In an additional analysis, Gilenya significantly delayed disability progression, defined as Confirmed Disability Progression (CDP), compared to interferon beta-1a.
“There is already substantial evidence that Gilenya is an effective treatment that improves long-term outcomes for adults with relapsing MS. We are delighted that PARADIGMS has shown such meaningful benefits for children and adolescents with MS,” said Vas Narasimhan, Global Head of Drug Development and chief medical officer, Novartis. “This pioneering study demonstrates our continued commitment to providing new treatment options to MS patients with the highest need. We look forward to working with health authorities and preparing for submission.”
Gilenya is not currently approved for the treatment of pediatric MS. Novartis is working on submission with health authorities worldwide.
The phase III PARADIGMS study (NCT01892722) is a flexible duration (up to two years), double-blind, randomized, multi-center study to evaluate the safety and efficacy of oral Gilenya compared to interferon beta-1a in children and adolescents with a confirmed diagnosis of multiple sclerosis (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 5.5. Patients were randomized 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.
The primary endpoint of the study was the frequency of relapses in patients treated up to 24 months (annualized relapse rate). 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 period.
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 Pediatric Multiple Sclerosis Study Group.