Dr Ralf GoldRalf Gold, MD
New 10-year study data set to be presented at the at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), September 11-13, 2019, in Stockholm, Sweden, suggest that treatment of multiple sclerosis (MS) with dimethyl fumarate (Tecfidera; Biogen) is associated with a low incidence of disease relapse and stable patient-reported outcomes.1

“Biogen’s new data underscore TECFIDERA’s role as a meaningful long-term therapy option for relapsing MS, with many patients in the study experiencing no relapses or progression in their disability over a 10-year period,” Alfred Sandrock Jr., MD, PhD, executive vice president and chief medical officer, Biogen, said in a statement.2

The data, pooled from the phase 3 DEFINE/CONFIRM clinical trial its ongoing extension (ENDORSE; NCT00835770), ultimately showed that the proportion of patients with an Expanded Disability Status Scale (EDSS) scores ≤3.5 remained stable over time and the number of patients with confirmed disability progression over 10 years remained low.

Additionally, Ralf Gold, MD, head, department of neurology, and dean of research, Ruhr University Bochum, and coauthors detailed that “there was no increased incidence of serious infections over time,” and that all told, “these results support the safety and efficacy of dimethyl fumarate as a long-term treatment option for patients with relapsing MS.”

In total, 618 patients had at least 10 years of follow-up data, and 192 were treated continuously twice daily. Gold and colleagues re-randomized 1:1 to dimethyl fumarate in a dose of 240 mg either twice or thrice daily. Measures of MS disease activity were recorded via relapse and CDP, as well as serious adverse events (SAEs), and patient-reported outcomes via the 36-item short-form health survey (SF-36) and 5-dimension QoL (EQ-5D).

In total, 98 patients (51%) retained freedom from relapse, while 43 (22%) had a single relapse. Meanwhile, 51 patients (26%) experienced ≥2 relapses over the 10-year treatment period. The median time to the first relapse was 518 weeks.

The mean baseline EDSS score was 2.24 (standard deviation [SD], 1.18). By year 2, 164 of 184 patients (89%) had an EDSS ≤3.5. By years 8 and 10, respectively, 148 (80%) and 146 (79%) had an EDSS ≤3.5. Over the 10-year period, 122 patients (64%) had no confirmed disability progression. For the measures from the SF-36 and EQ-5D, from baseline to year 10, patients generally remained stable.

With regard to SAEs, 77 patients (40%) experienced ≥1, most of which (n = 34; 44%) were disease relapse or infection (n = 12; 16%). Over the 10-year period, there was no increased incidence of serious infection, ranging from 0% to 2%, with most years experiencing a 1% incidence (≤2 cases).

“We are proud of the strong legacy Tecfidera has achieved over the years and are excited to continue building our franchise of fumarate products with the potential addition of diroximel fumarate,” Sandrock, Jr. said. “As a next-generation fumarate, diroximel fumarate offers a differentiated gastrointestinal tolerability profile and, if approved, will be a strong choice for physicians and patients with relapsing MS to consider.”

In the original findings from the DEFINE/CONFIRM studies, the data showed significantly higher levels of no evidence of disease activity (NEDA) status compared to patients administered placebo. Ultimately, over 2 years, there was a 38.9% reduction in clinical NEDA (hazard ratio [HR], 0.61; 95% CI, 0.52–0.72; P <.0001) in the intent-to-treat group (n = 1540), while the MRI population (n = 692) showed a 40% relative reduction in neuroradiological NEDA (HR, 0.60; 95% CI, 0.49–0.73; P <.0001). Additionally, the percentage of patients achieving overall NEDA in the MRI cohort was also higher with dimethyl fumarate (26%) versus placebo (12%), with a relative risk reduction of 42.7% (HR, 0.57; 95% CI, 0.48–0.69; P <.0001).3

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REFERENCES
1. Gold R, Giovanni G, Philips JT, et al. Overall safety and efficacy through 10 years of treatment with delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis. Presented at: ECTRIMS; September 11–13, 2019; Stockholm, Sweden. Poster P1397.
2. New Data Presented at ECTRIMS Reinforce Long-term Benefits of TECFIDERA® (dimethyl fumarate) Over 10 Years [press release]. Cambridge, MA: Biogen; Published September 11, 2019. globenewswire.com/news-release/2019/09/11/1913968/0/en/New-Data-Presented-at-ECTRIMS-Reinforce-Long-term-Benefits-of-TECFIDERA-dimethyl-fumarate-Over-10-Years.html. Accessed September 11, 2019.
3. Havrdova E, Giovannoni G, Gold R, et al. Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies. Eur J Neurol. 2017;24(5):726-733. doi: 10.1111/ene.13272.