Tecfidera Works Better Than Avonex to Ease MS in Children in Trial
In rare MS type, Phase 3 trial data show reduced lesions, fewer relapses
Among children and adolescents with multiple sclerosis (MS), treatment with Tecfidera (dimethyl fumarate) resulted in less disease activity on MRI scans and fewer relapses, compared with Avonex (interferon beta-1a), according to new data from the CONNECT Phase 3 trial.
Researchers noted the lack of disease-modifying therapies (DMTs) available for treating pediatric patients with MS.
“With few approved multiple sclerosis therapies in the pediatric population, there is a need for further approved treatment options,” the team wrote, adding, “Given the highly active and inflammatory disease course of [pediatric-onset MS], with frequent relapses in the first years … there is a need for treatments that are effective at reducing inflammatory disease activity early in the disease course.”
Results from the trial were published in JAMA Network Open, in a study titled “Effect of Dimethyl Fumarate vs Interferon [beta]-1a in Patients With Pediatric-Onset Multiple Sclerosis: The CONNECT Randomized Clinical Trial.” The work was funded by Biogen, which markets Tecfidera.
Pediatric-onset multiple sclerosis, or POMS, is a rare condition in which symptoms of MS develop during childhood and adolescence. These patients commonly have a more active disease than adults, with more inflammatory activity on MRI scans and higher rates of relapse.
Because POMS is so rare, there have been few formal clinical trials studying treatments in children with MS. Thus, only a few disease-modifying treatments are approved for these patients, with most being used off-label.
Investigating Tecfidera vs. Avonex
Tecfidera is approved in the U.S. to treat adults with relapsing types of MS. The oral medication works to reduce the inflammatory attack on the nervous system that drives the disease.
To investigate the medication’s safety and efficacy in younger patients, Biogen sponsored a Phase 3 clinical trial, called CONNECT (NCT02283853). The trial, involving 156 children and adolescents, compared Tecfidera against Avonex, an injectable MS medication also approved only for adults.
The participants ranged in age from 10 to 17 (median 15 years), were 67.3% female, and had relapsing-remitting MS. Each was randomly assigned to receive one of the two medications for 96 weeks, or about two years.
Tecfidera was administered by mouth at a dose of 120 mg twice daily for the first week, and 240 mg twice daily thereafter. Avonex was given via weekly injection into the muscle, with increasing doses in the first few weeks up to a maintenance dose of 30 micrograms/week.
Of the 156 patients initially randomized, 150 received treatment in the study, and 103 completed the 96-week trial — only these participants were included in the main efficacy analyses.
The most common reasons for stopping treatment early were voluntary withdrawal, side effects, and investigator recommendation. The researchers noted that more participants given Tecfidera than Avonex ended up completing the trial (79.5% vs. 56.9%).
The study’s main goal was to assess the proportion of patients who did not have any new or enlarging MS lesions over the course of the entire study. This percentage was markedly higher among patients on Tecfidera than Avonex (16.1% vs. 4.9%), with patients on Tecfidera having 62% fewer new or enlarging lesions over the two-year period than those on Avonex.
Additional sensitivity analyses that looked at data for all patients treated in the trial, not just those who finished the study, were largely consistent in showing better outcomes with Tecfidera.
Relapse rates also were significantly lower on Tecfidera than Avonex (0.24 vs. 0.53), and more patients on Tecfidera were relapse-free over the course of the entire study (66.2% vs. 52.3%), though the difference did not reach statistical significance. The team speculated that greater apparent efficacy in terms of relapse rates was likely a contributing factor in why more patients on Tecfidera completed the study.
New treatments needed for POMS
The researchers stressed that, given the rarity of POMS, this study was not designed to have the statistical power to definitively compare the efficacy of these two medications. Nonetheless, they said the results showed that treatment with Tecfidera, “led to meaningful improvements in radiological and clinical outcomes in patients with POMS, with a positive benefit-risk balance.”
Safety and tolerability data from this trial were generally in line with the known profiles of both medications: Avonex was commonly associated with flu-like side effects, while the most common side effects associated with Tecfidera were digestion-related.
A noted limitation of this trial is that it was open-label, meaning participants were aware of which treatment they were being given, which could lead to biases that influence the results.
The CONNECT trial is still ongoing. Those who completed the first part will now be followed for up to five more years in a second portion, which aims to determine the medication’s long-term safety and efficacy in POMS patients.
“A shift from a focusing on short-term [treatment] safety profiles to longer-term safety assessment (including in prepubescent patients) is recommended to ensure that treatment early in life does not expose patients to future risk. We are looking forward to part 2 of the long-term outcomes of dimethyl fumarate in patients with POMS who completed the 96-week part of the trial,” a trio of U.K. researchers wrote in an accompanying commentary.