Gilenya (fingolimod) was seen to significantly reduce relapses in children and teenagers with multiple sclerosis (MS), according to data from a Phase 3 study — the first successfully conducted in pediatric patients.
Novartis, the therapy’s developer, is preparing to file requests for Gilenya to be approved to treat pediatric patients in the U.S. and Europe based on these results.
The PARADIGMS trial (NCT01892722) is evaluating the efficacy of a disease-modifying therapy in MS patients ages 10 to 17, a population both difficult to study and to treat. The double-blind and randomized trial followed patients with active and relapsing MS for up to two years, followed by a five-year and open-label extension period that may run through 2023.
The positive findings were part of the oral presentation “PARADIGMS: a randomised double-blind study of fingolimod versus interferon β-1a in paediatric multiple sclerosis,” given by Tanuja Chitnis, with Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital, Boston, on the closing day of the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris.
Gilenya is approved by both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) to treat adults with RRMS. The oral therapy is known to control four measures of disease activity in these patients — relapses, MRI lesions, brain volume loss, and disability progression — but its potential benefit to children was not known.
PARADIGMS enrolled 215 pediatric RRMS patients (mean age, 15.3), all with short disease duration (mean of 1.2 years) and high disease activity, at 87 clinical centers across 25 countries. Each had experienced at least one relapse in the previous year or two relapses in the previous two years, or have developed brain lesions within six months prior trial initiation.
The children were randomly assigned to receive once-daily oral administration of 0.5 mg or 0.25 mg of Gilenya, according to their body weight, or once weekly intramuscular injections of Biogen’s Avonex (interferon beta-1a), as a comparator treatment.
Results showed Gilenya significantly lowered relapse rates compared to Avonex.
“Fingolimod was superior to interferon beta-1a in reducing annualized relapse rate up to month 24 in pediatric patients with MS,” Chitnis said. This reduction was a reported 81.9%.
Gilenya also significantly delayed the time-to-first confirmed relapse. “85.7% of patients in the fingolimod group were free of confirmed relapse at month 24 versus 38.8% on the interferon beta-1a group,” Chitnis reported.
Time to three-month confirmed disability progression (CPD) was also significantly delayed with Gilenya treatment, she said, with “95.2% of patients in the fingolimod group … free of three-month CPD at month 24 versus 84.7% on interferon beta-1a group.”
This delay was also sustained through to the study’s end. A “significant risk reduction of 77.2% in three-month CDP over 24 months was observed with fingolimod versus interferon beta-1a,” Chitnis said.
Gilenya was also found to be superior to Avonex in magnetic resonance imaging (MRI) outcomes. “Fingolimod significantly reduced the annual rate of brain atrophy from baseline up to month 24, versus interferon beta-1a (-0.48 versus -0.80),” Chitnis said.
Gilenya-treated patients also showed fewer lesions on MRIs than those given Avonex.
In terms of safety, more adverse events were seen in the Avonex group (95.3%) than in the Gilenya group (88.8%). Most of these were upper respiratory tract infections, pyrexia (fever), influenza (the flu) and influenza-like illnesses.
However, more serious adverse events were seen in the Gilenya group (17.8%) compared to Avonex (9.3%), namely leukopenia (low white blood cell counts), seizure, and hypersensitivity. This safety profile is comparable to that seen in adult clinical trials of Gilenya.
“PARADIGMS is the first successfully completed Phase 3 randomized controlled trial of pediatric patients with MS globally,” Chitnis concluded. “PARADIGMS study met its primary endpoint, showing a significant reduction in relapses with fingolimod versus interferon beta-1a.”
According to Chitnis, “3 to 5 percent of all patients with MS have a pediatric onset.” The great majority of these patients have relapsing-remitting multiple sclerosis (RRMS), and their relapse rates are 2 to 3 times higher than that seen in people with adult-onset MS.
Multiple Sclerosis News Today had the opportunity to interview Danny Bar-Zohar, global development head of neuroscience at Novartis, at the ECTRIMS-ACTRIMS Meeting. Bar-Zohar spoke about Gilenya and the PARADIGMS trial. To watch the full interview, please visit this link.