Teriflunomide Study in Kids with MS Does Not Meet Primary Endpoint, But Reduces MRI Activity

—Do We Need Different Ways to Measure Treatment Effectiveness in Children with MS?In a recently published study of 155 children and teens with MS, teriflunomide (Aubagio^®, Sanofi Genzyme) did not reduce the time to a relapse significantly more than placebo, the primary endpoint of the study. However, teriflunomide did reduce disease activity on MRI scans, which were secondary endpoints. An accompanying editorial suggests the need for alternative trial designs to show that therapies approved to treat MS in adults are also effective in children with the disease.

• Some estimates suggest that up to five percent of cases of MS begin prior to adulthood. Pediatric MS generally manifests as active relapsing-remitting disease. There is only one MS disease-modifying therapy approved by the U.S. Food and Drug Administration to treat children: Gilenya^® (fingolimod, Novartis AG).
• The trial enrolled participants aged 10-17 years, diagnosed with relapsing MS and with at least one relapse in the preceding year or at least two relapses in the two preceding years. Participants were randomly assigned to oral teriflunomide (102 participants) or placebo (53 participants) for up to 96 weeks. Participants with “breakthrough” disease were eligible to enter an open-label extension phase, where everyone would receive teriflunomide. The primary goal of the study was the time to first confirmed clinical relapse. Key secondary endpoints included disease activity on MRI scans.
• After 96 weeks, there was no difference in time to first confirmed clinical relapse with teriflunomide compared with placebo. Teriflunomide did reduce disease activity on MRI scans significantly more than placebo.
• Mild to moderate infections were the most frequently reported adverse event in both treatment groups, with a higher rate observed in the teriflunomide group. Three participants had pancreatic adverse events during the double-blind period, unlike trials involving adult patients. The authors suggest that this would require vigilance if prescribing teriflunomide to children.
• Regulators require standard phase 3 trials based on clinical endpoints to assess the effectiveness of treatments approved in adults for children and teens with MS. In an accompanying editorial, Drs. Maria Pia Sormani (University of Genoa) and Emmanuelle Waubant (University of California, San Francisco) note that this study highlights “the need for a different strategy to test and approve drugs for children once they are approved for adults.”
• The authors of the editorial suggest that this regulatory requirement might not benefit children with MS as it results in longer trials that might not recruit enough participants to demonstrate a significant improvement from a given therapy. This could potentially limit the number of approved treatment options for children and adolescents with MS. They cite suggestions from the International Pediatric MS Study Group, including using MRI-related endpoints as the primary endpoint and enrolling teenagers in adult trials.

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