Long-term treatment with Tecfidera (dimethyl fumarate) safely and effectively reduces the frequency of relapses in children with relapsing-remitting multiple sclerosis (RRMS), according to 2.5 years of data from the FOCUS Phase 2 trial and its extension study.
The study, “Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis,” was published in the journal Frontiers in Neurology.
MS in children is rare, with around 10,000 worldwide estimated to have pediatric-onset multiple sclerosis. Most of these patients have RRMS, and tend to have a higher frequency of relapses and related hospitalizations than their adult counterparts.
“Adequate long-term safety and efficacy data on DMTs [disease-modifying therapies] for the pediatric population are limited, resulting in a shortage of approved MS-specific treatment options in this patient population,” the researchers wrote.
Novartis’ Gilenya (fingolimod) is currently the only DMT approved in both the U.S. and Europe for pediatric MS patients, ages 10 and older. As such, there is an unmet need for long-term clinical data evaluating MS therapies in children and adolescents.
Marketed by Biogen, Tecfidera is an oral DMT approved to treat relapsing MS. It is thought to work by lowering inflammation and oxidative stress — cell damage caused by high levels of oxidant molecules.
While its favorable benefit-risk profile in adults with RRMS has been extensively shown in both clinical trials and real-world studies, evidence of its safety and effectiveness in pediatric patients is limited.
The Biogen-sponsored, and international FOCUS Phase 2 study (NCT02410200) evaluated Tecfidera’s safety, pharmacokinetics (its movement into, through, and out of the body), and effectiveness in 22 pediatric patients, ages 13–17, with RRMS.
Results from the 20 participants who completed the six-month treatment showed that the therapy significantly reduced the number of new or enlarging brain lesions. Its safety and pharmacokinetics profiles were also consistent with those observed in adult patients.
After finishing FOCUS, all 20 patients chose to enter its long-term, extension study, called CONNECTED (NCT02555215), in which they continued to receive Tecfidera (240 mg twice daily) for an additional two years.
Newly published data concern the final CONNECTED’s results. The trial’s main goal was to assess several safety measures, while secondary goals included changes in brain lesions, MS relapse frequency — assessed through the annualized relapse rate (ARR) — and disability, based on patients’ scores on the expanded disability status scale (EDSS).
At enrollment, most participants were girls (65%) ages 17 or 18 (65%). About half of them had received previous MS treatment before entering FOCUS, with the most common (35%) being Rebif (interferon beta-1a).
These pediatric patients were given Tecfidera for a median of 99.4 weeks (nearly two years) on FOCUS and CONNECTED combined, with a high treatment compliance. Seventeen of the initial 20 enrolled (85%) completed the CONNECTED extension study; three withdrew after new brain lesions were detected on MRI scans.
Results showed that 71% of participants with MRI data from weeks 16–24, and 80% of those with available data from weeks 64–72 had no new or enlarged brain lesions. Tecfidera was also associated with a continued reduction in relapses and ARR.
Patients’ ARRs dropped from 1.5 annual relapses in the year prior to FOCUS entry, to 0.6 during FOCUS, and 0.1 across CONNECTED. During the full 2.5 years of treatment, the ARR was 0.2, representing an 84.5% reduction relative to the year before Tecfidera initiation.
EDSS scores also remained generally low (no or minimal disability) and stable. Three (15%) participants showed signs of disease progression.
There were no unexpected observations regarding adverse events, clinical laboratory parameters, or vital signs.
Adverse events were reported for most (90%) patients, with the most common being flushing (25%). The majority of these side effects were mild or moderate. Three patients had four serious adverse events, but none led to treatment discontinuation.
Taken together, Tecfidera’s long-term safety and effectiveness data “confirmed and extended the findings from the 24-week FOCUS study,” the researchers wrote. They were also consistent with those reported in adults, “suggesting pediatric and adolescent patients with MS might benefit from [Tecfidera] treatment,” the team added.
The researchers also noted that results from an ongoing Phase 3 trial (NCT02283853) evaluating the safety and effectiveness of Tecfidera against Rebif in 156 MS patients, ages 10–17, may help in further establishing Tecfidera’s suitability for pediatric patients.
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