FDA grants 'Breakthrough Therapy' designation to fingolimod for pediatric MS

The Food and Drug Administration (FDA) has granted a “Breakthrough Therapy” designation to the oral agent fingolimod—a sphingosine 1-phosphate receptor modulator—for the treatment of children and adolescents aged 10 years and older with relapsing multiple sclerosis (MS).

Worldwide, MS affects more than 2.3 million people, most of whom are diagnosed between the ages of 20 and 50 years. The disorder occurs in women at least two to three times more frequently than in men. In 2010, the FDA approved fingolimod for the treatment of adults with relapsing forms of MS. In pediatric patients with relapsing MS, however, no treatment is currently available.

Novartis Pharmaceuticals has filed for approval of fingolimod to treat pediatric MS. The FDA granted fingolimod a “Breakthrough Therapy” designation based on results from the phase 3 PARADIGMS trial, presented in October 2017 at the 7th Joint European Committee for Treatment and Research in MS (ECTRIMS)/Americas Committee for Treatment and Research in Multiple Sclerosis meeting, Paris, France.

“Approximately 3%?5% of all patients with MS have disease onset before 18 years of age. These pediatric patients have a 2 to 3 times higher relapse rate than patients with adult-onset MS. The PARADIGMS trial is the first global, controlled trial investigating the efficacy and safety of fingolimod in pediatric patients with MS,” wrote the researchers, led by Tanuja Chitnis, MD, associate neurologist, Brigham and Women’s Hospital, and associate professor of neurology, Harvard Medical School, Boston, MA.

In the PARADIGMS study, Dr. Chitnis and colleagues assessed the efficacy and safety of fingolimod (up to 0.5 mg/d) compared with interferon (IFN) beta-1a (30 µg IM) in pediatric patients with relapsing-remitting MS. They reported results from the first 190 randomized patients (mean age: 15.3 years; 88% white non-Hispanic; 63% female). Subjects had a mean disease duration of 1.2 years and, during the 12 months before screening, 1.5 mean relapses. In addition, they had a mean of 3.1 gadolinium-enhancing (Gd+) T1 lesions and a median Expanded Disability Status Scale (EDSS) score of 1.5.

In children and adolescents, fingolimod reduced the annual number of MS relapses by 82% over 2 years, compared with interferon beta-1a. After 2 years, a full 86% of children on fingolimod had not relapsed, compared to 39% of those treated with IFN beta-1a. Researchers also found evidence on MRI of benefits in patients treated with fingolimod, and a side effect profile comparable to that seen in adults.

This study is supported by Novartis Pharma AG, Basel, Switzerland. Dr. Chitnis has received personal compensation for advisory boards/consulting for F. Hoffman-La Roche, Biogen, and Novartis Pharmaceuticals and financial support for research activities from Biogen, Merck Serono, Verily, and Novartis Pharmaceuticals.