Tecfidera: A Novel Pathway for MS

A new drug to treat multiple sclerosis has the potential to drive spending increases in the specialty category.

The FDA recently announced the approval of Tecfidera (dimethyl fumarate)—also known in its development stages as BG-12—to treat patients with relapsing forms of multiple sclerosis (MS).

Working through a novel mechanism and boasting a notably clean adverse effects profile on its label, Tecfidera is likely to be a new blockbuster specialty treatment for MS.

Although Tecfidera’s exact mechanism of action is unknown, activation of the novel pathway via Nrf-2 is thought to defend neurons against inflammation and oxidative stress caused by the disease. Oxidative stress can cause problems in the normal mechanisms of cellular signaling, and the damage that can be caused by inflammation is well known. Specifically, oxidative stress triggers the activation of the Nrf-2-antioxidant response element signaling pathway, which controls the expression of genes whose protein products are involved in the detoxication and elimination of reactive oxidants and free radicals. Simply put, the Nrf-2 pathway is protective in nature and its activation is essential to maintain homestasis within cells.

The fact that Tecfidera’s mechanism of action is unknown may seem troubling, but it is not unusual. Most drugs currently marketed to treat MS, including Copaxone (glatiramer acetate injection) and interferon, also have largely unknown mechanisms of action—and this has not appeared to hinder their success, says GlobalData analyst Paul Su. “Prior to Tecfidera, there were currently 9 FDA-approved MS disease-modifying therapies, and I would say about 7-8 of these have a mechanism of action that is not entirely understood,” stated Su in an email to Specialty Pharmacy Times.

Just because a drug’s mechanism is not known does not necessarily make the drug unsafe, added Su. Clinical trials for Tecfidera have not suggested any serious adverse events, and its current safety profile is “mild,” with the most common side effects being flushing and gastrointestinal events such as nausea and diarrhea. Even so, “[w]ith Tecfidera, excessive transcription of antioxidative genes (via Nrf-2) could possibly increase the risk of malignancies, while the anti-inflammatory effects of the drug could perhaps increase the risk of infections,” noted Su.

Competing MS treatments Gilenya (fingolimod) and Aubagio (teriflunomide) have been associated with more serious adverse events, and Tecfidera is thought to have a more favorable safety profile. “With regards to Gilenya, there are safety concerns with cardiovascular adverse events and possible immunosuppressive effects, meaning patients have to be monitored closely for a period of time,” wrote Su. “Aubagio has a black box warning due to potential hepatotoxicity and teratogenicity.”

Su noted that physicians may not be overly concerned with the lack of post-marketing surveillance on Tecfidera, as its active metabolite dimethyl fumarate is present in Fumaderm (fumaric acid esters), a drug that has been used in Germany to treat psoriasis since 1994.

Tecfidera’s price may also make it an attractive therapy candidate for some MS patients. The drug’s manufacturer, Biogen Idec, has announced it will charge $54,900 a year for the medication—more than Aubagio ($45,000 per year) and less than Gilenya ($58,000 per year).

Gilenya and Aubagio may still have a slight advantage over Tecfidera, however. All 3 drugs are orally administered, but Tecfidera requires a twice-daily dosing frequency, “or even 3 times daily based on clinical trials,” Su asserted. This dosing regimen may affect adherence and could potentially make Gilenya and Aubagio more appealing than Tecfidera to patients based on ease of use.

The buzz around Biogen Idec’s new therapy has been circulating for months, and uptake of the drug is expected to be strong. According to Su, “a lot of physicians/patients held off starting treatment with current MS drugs” to wait for Tecfidera to become available.

“Tecfidera will influence the current landscape—time will tell whether this is adopted for wide use as we follow post-marketing data,” said Monalisa Mohanty, RPh, director of specialty clinical marketing at Express Scripts. “As a standard practice, we will monitor utilization after the drug is launched.”