Impressive Results With Fingolimod in Pediatric MS

November 01, 2017

PARIS — The oral multiple sclerosis (MS) drug fingolimod (Gilenya, Novartis) has shown impressive results in the pediatric population, with large reductions in relapse rate, new MRI lesions, brain atrophy, and disability progression compared with interferon β in the PARADIGMS trial.

The study was presented here at last week's 7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting.

Noting that there are currently no US Food and Drug Administration (FDA)–approved MS therapies for the pediatric population, lead investigator, Tanuja Chitnis, MD, director of the Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital, Boston, said, "We are encouraged by the reduction in the annualized relapse rate we've seen with fingolimod in this study."

She added that 3% to 5% of all patients with MS have pediatric onset, and PARADIGMS was designed specifically for pediatric patients, who often have more frequent relapses than adults with early MS.

The study was greeted with much enthusiasm from outside experts.

Commenting for Medscape Medical News, Jeremy Chataway, MD, University College London, United Kingdom, said, "This is very exciting — the first randomized controlled trial in the pediatric MS population. It showed clear superiority of fingolimod over β-interferon, and fingolimod should now become standard of care."

"It also shows randomized trials can be done in the pediatric MS population, potentially opening the door for others to follow suit," he added.

In a review of the highlights of the ECTRIMS conference, Robert Fox, MD, Cleveland Clinic, Ohio, said, "This trial gives us assurance and comfort that at least one drug used in adult multiple sclerosis is applicable to younger patients. I look forward to seeing longer-term safety data."

Bernhard Hemmer, MD, head of the Department of Neurology at the Technical University in Munich, Germany, said, "I was very impressed with this study and I think the treatment effects are very profound."

Dr Hemmer added that other trials in adult MS were also suggesting that therapies appear to be more effective in younger patients. "It is all pointing towards early diagnosis and early treatment — and less of an effect later on when the patient gets older and especially gets into secondary progression."


The phase 3 PARADIGMS trial was a double-blind, randomized, multicenter study in which 215 children and adolescents aged 10 to 18 years and with a confirmed diagnosis of relapsing MS were randomly assigned to once-daily oral fingolimod (0.5 mg or 0.25 mg, dependent on body weight) or intramuscular interferon β-1a once weekly.

The mean duration of study drug exposure was 18 months, and 93% of patients receiving fingolimod and 81% of those receiving interferon completed this core phase; 88% and 70%, respectively, entered an extension phase on open-label fingolimod.

The primary endpoint of the study was the frequency of relapses (annualized relapse rate) in patients during the randomized study phase. The rate was 0.67 in the interferon β group vs 0.12 in the fingolimod group, a 82% relative risk reduction (P < .001).

Other results showed that 85.7% of patients in the fingolimod group were free of confirmed relapse for the entire study duration compared with 38.8% of patients with in the interferon β group.

Fingolimod treatment was also associated with a favorable effect on MRI endpoints, with a 52% reduction in annualized rate of new T2 lesions and a 66% reduction in the number of gadolinium-enhancing T1 lesions per scan.

Fingolimod also significantly reduced brain atrophy from baseline compared with interferon β (change, –0.48 vs –0.80; P = .014).

There was also a significant 77% reduction in 3-month confirmed disability progression over 24 months with fingolimod vs interferon β  (P < .007), with 95% of fingolimod recipients free of 3-month confirmed disability progression at month 24 vs 84.7% of those receiving interferon.  

Serious adverse events occurred in 17.8% of fingolimod recipients  vs 9.3% of interferon recipients. The serious adverse events in the fingolimod group included four cases of seizures/epilepsy, two cases of leukopenia, one case of agranulocytosis, one case of second-degree atrioventricular block, and one case of hypersensitivity. Overall, adverse events occurred in 95% of the interferon group and 88% of the fingolimod group.

Dr Chitnis said the safety profile of fingolimod in the PARADIGMS trial was consistent with that seen in adult clinical trials.

PARADIGMS was conducted in 87 sites in 25 countries, and was designed in partnership with the FDA, European Medicines Agency, and International Pediatric Multiple Sclerosis Study Group.

PARADIGMS was supported by Novartis. Dr Chitnis has received personal compensation for advisory boards/consulting for Roche, Biogen, and Novartis and financial support for research activities from Biogen, Merck Serono, Verily, and Novartis.

7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting. Abstract 276. Presented October 28, 2017.

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