The FDA has expanded the indication for fingolimod to include the treatment of children and adolescents age 10 years and older with relapsing multiple sclerosis.
Brenda L. Banwell, MD
The FDA has expanded the indication for fingolimod (Gilenya) to include the treatment of children and adolescents age 10 years and older with relapsing multiple sclerosis (MS), making immunomodulating drug the first agent specifically approved to treat MS in pediatric patients.
The approval was based on the phase III PARADIGMS study, in which fingolimod demonstrated a significant improvement in the primary endpoint of annualized relapse rate (ARR) compared with interferon beta-1a. The ARR with fingolimod was 12.2% compared with 67.5% with interferon beta-1a, representing an 81.9% relative reduction in ARR.
"We now finally have an FDA-approved treatment for children and adolescents with relapsing MS," co-investigator of the study Brenda L. Banwell, MD, chief of the Division of Neurology at Children's Hospital of Philadelphia, said in a statement. "Repeated relapses are more common in young people with MS than in adults, so this is heartening news for patients and their families."
In the study, 215 patients with relapsing-remitting MS were randomized to once-daily fingolimod (n = 107) or intramuscular interferon beta-1a (n = 108). One patient in the interferon beta-1a arm received treatment but was excluded from the efficacy analysis. Overall, 6.5% of those in the fingolimod arm did not complete the trial (median exposure, 634 days) compared with 18.5% in the comparator arm who did not finish (median exposure, 547 days).
The median age of patients at baseline was 16 years, and the median disease duration since first symptom was 1.5 years. Patients less than or equal to 40 kg received fingolimod at 0.25 mg with or without food. Those weighting more than this could receive the treatment at 0.5 mg.
In addition to improvements in ARR, 86% of patients remained relapse-free at 24 months with fingolimod. This was nearly double the rate seen with interferon beta-1a. In this arm, 45.8% of patients were relapse-free at 24 months.
The annualized rate of new or newly enlarging T2 lesions was 4.393 with fingolimod compared with 9.269 with interferon beta-1a, presenting a 52.6% reduction in (P <.001). The mean number of Gd-enhancing T1 lesions per scan up to month 24 was 0.436 compared with 1.282, for fingolimod and interferon beta-1a, respectively, which was a 66% relative reduction with the investigational therapy (P <.001).
The safety profile seen with fingolimod in the pediatric trials was like what has been observed with the agent in adult patients, for which fingolimod was first approved in 2010. The most frequently reported adverse events were headache, liver enzyme elevation, diarrhea, cough, flu, sinusitis, back pain, abdominal pain, and pain in extremities. In pediatric studies, 5.6% of patients reported seizures with fingolimod compared with 0.9% with interferon beta-1a.
“For the first time, we have an FDA-approved treatment specifically for children and adolescents with multiple sclerosis,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “Multiple sclerosis can have a profound impact on a child’s life. This approval represents an important and needed advance in the care of pediatric patients with multiple sclerosis.”