Two years of treatment with oral Gilenya (fingolimod) significantly reduced the rate of relapses when compared to Avonex (interferon beta-1a) intramuscular injections in children and adolescents with relapsing forms of multiple sclerosis (RMS), according to Phase 3 clinical trial results.
Additionally, Gilenya (marketed by Novartis) decreased the number of central nervous system (CNS) lesions as observed with magnetic resonance imaging (MRI) over the same period.
“I’d like to thank all the children who participated in the PARADIGMS study, and their families, who have helped transform the outlook for pediatric patients living with relapsing MS,” Tanuja Chitnis, principal study investigator and director of the Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital, Boston, said in a press release.
“These data, published today, will go a long way in helping to advance knowledge and understanding amongst the MS community of how to evaluate and treat pediatric patients,” added Chitnis, who is also affliliated to the Ann Romney Center, Brigham and Women’s Hospital, Boston.
Young MS patients are burdened with more frequent and more severe relapses, affecting their ability to enjoy childhood and adolescence and promoting feelings of anxiety and isolation.
In the PARADIGMS study (NCT01892722), relapsing patients ages 10 to 17 were randomized to receive Gilenya – administered orally at a dose of 0.25 milligrams (mg) or 0.5 mg per day, depending on the child’s weight – or intramuscular injections of Avonex (marketed by Biogen) at a dose of 30 micrograms per week.
Patients were treated for up to two years. Long-term Gilenya use is under study in children continuing in the trial’s five-year open-label extension.
PARADIGMS enrolled 215 patients with an Expanded Disability Status Scale (EDSS) score between 0 and 5.5 – EDSS ranges from 0 to 10, with higher scores indicating more severe disability.
Its primary goal was changes in annualized relapse rates, i.e., the number of confirmed relapses per year in each group of patients 24 months after treatment began. Additional (secondary) endpoints included the number of new or newly enlarged T2 lesions, gadolinium-enhancing T1 lesions, the time to the first relapse, and the safety and pharmacokinetic properties of Gilenya. Pharmacokinetics refers to a drug’s absorption, bioavailability, distribution, metabolism, and excretion in the body.
In total, 107 patients were assigned to Gilenya and 108 to Avonex. Patients had a mean of 2.4 relapses in the two years preceding the trial.
Data showed that Gilenya significantly reduced the rate of annual relapses to 0.12 while in the Avonex group the rate was of 0.67 – an 82% difference between both therapies.
Moreover, 85.7% of Gilenya-treated patients were relapse-free at two years, compared to 38.8% of those given Avonex.
The number and volume of CNS lesions are linked to the number of relapses and disability rates in children and adolescent with RMS.
Gilenya significantly reduced the number of new or newly enlarged T2 lesions by 53% – the annual rate of new lesions was of 4.39 with Gilenya and 9.27 with Avonex– and the average number of gadolinium-enhancing T1 lesions per scan at two years by 66% – 0.44 with Gilenya and 1.28 with Avonex.
Treatment with Gilenya also significantly reduced the annual rate of brain shrinkage, or atrophy, by 40%.
The safety profile of Gilenya was similar to that seen in previous trials. Adverse events were more frequent in the Avonex group (95.3%) than the Gilenya group (88.8%), but in the Gilenya group the rate of serious advserse events was higher – 6.5% versus 16.8%, respectively.
Eighteen patients using Gilenya had serious adverse events, which included infection (four patients) and a drop in the number of white blood cells (two patients).
The study’s authors noted that “longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis.”
Gilenya recently became the first disease-modifying therapy approved by the U.S. Food and Drug Administration (FDA) to treat children and adolescents with relapsing MS, starting at age 10.
This study was supported by Novartis,and four of its 18 authors are Novartis employees.