Since its approval by the U.S. Food and Drug Administration (FDA) in 2013, Tecfidera (dimethyl fumarate) has emerged as a first-line treatment for relapsing-remitting multiple sclerosis (RRMS), the most common form of multiple sclerosis (MS).
While two separate clinical trials demonstrated Tecfidera’s ability to significantly reduce both the rate of relapse and disease progression associated with RRMS, the long-term effectiveness and safety of this oral therapy has remained unclear. Its specific mechanism of action is also largely unknown. Reports released in the last few months, however, offer encouraging new findings into the drug’s long-term efficacy and safety, while others are beginning to uncover its workings.
In a recent presentation at the 68th annual meeting of the American Academy of Neurology, Biogen, the company responsible for developing and commercializing Tecfidera, announced positive results regarding the long-term effectiveness of the drug, as reported by Multiple Sclerosis News Today. Newly diagnosed RRMS patients receiving Tecfidera treatment maintained consistently reduced relapse rates over the course of the trial. Specifically, over 50 percent of the patients exhibited no relapses through six years of treatment. Tecfidera’s long-term safety profile was also supported.
Of Biogen’s three Phase 3 trials evaluating Tecfidera to treat RRMS, one is continuing as an extension monotherapy study — ENDORSE (NCT00835770) — and will monitor the effectiveness and safety of the therapy through mid-2019.
The effectiveness of Tecfidera was also assessed using real-world data from a U.S. health claims database. When compared to glatiramer acetate (Copaxone), interferon β, fingolimod (Gilenya), and teriflunomide (Aubagio), four alternative MS medications, Tecfidera was reported to be more effective in reducing relapse rates than three of these alternative medications, with only fingolimod exhibiting similar effectiveness. The increased effectiveness of Tecfidera as compared to interferon β and glatiramer acetate is particularly advantageous, as these two therapies are given by injection rather than oral administration.
“The MS treatment landscape has expanded rapidly in recent years, giving physicians and patients options for various stages of disease,” Kate Dawson, MD, vice president, U.S. Medical group at Biogen, said in a press release. “These data show TECFIDERA consistently delivers strong and sustained efficacy in newly diagnosed patients both in a real-world and clinical setting, further supporting the value it offers patients and affirming the advantages of early treatment with TECFIDERA in decreasing clinical disease activity.”
For more information, visit our resource page for TECFIDERA (Dimethyl Fumarate).
Current research studies are also beginning to advance our understanding of Tecfidera’s mechanism of action, specifically regarding its immunomodulatory properties.
Tecfidera treatment reduces the overall level of B-cells, a type of immune cell. But there are several different subsets of B-cells, each with differing functions. Multiple Sclerosis News Today recently reported on a new study, from researchers at the University of Michigan Medical School, showing that while a subset of B-cells, including naive and memory B-cells, were decreased in RRMS patients during Tecfidera treatment, two types of regulatory B-cells significantly increased in levels after 12 months. These regulatory B-cells, T2-MZP and B-1, are able to produce the anti-inflammatory factor known as IL-10. Overall, this study demonstrated that Tecfidera affects B-cell subtypes differentially, appearing to favor an increase of IL-10-producing regulatory B-cells. Given these data, more studies are needed to determine if the increase in regulatory B-cells specifically contributes to the beneficial outcomes seen in Tecfidera use.
Researchers think that a major mechanism by which Tecfidera ameliorates MS symptoms is via activation of the Nrf2 pathway. This pathway plays a role in resolving excess inflammation and oxidative stress, both of which contribute to MS. But precisely how the Nrf2 pathway is activated by Tecfidera, and how this activation leads to the reduced relapse rate in RRMS patients, continues to puzzle.
Recently, Multiple Sclerosis News Today reported that an animal study, led by Ulf Schulze-Topphoff of the Department of Neurology at UC San Francisco, demonstrated that Tecfidera treatment reduced MS-related immune system reactions independently of Nrf2. This study encourages further research to consider alternative mechanisms by which Tecfidera modulates the immune response in MS.
Overall, our understanding of the long-term effectiveness, safety and feasibility, as well as the mechanism of action, of the oral medication Tecfidera has dramatically improved in the past few months. With this progress in mind, further advances in Tecfidera therapy for RRMS patients are surely on the horizon.