FDA Approves Diroximel Fumarate to Treat Relapsing Forms of MS

The FDA today approved Biogen and Alkermes’ diroximel fumarate, an oral agent, to treat relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and secondary progressive disease. The drug, approved under the 505(b)(2) regulatory pathway on the basis of its bioequivalence to dimethyl fumarate (Tecfidera), will be sold as Vumerity.

The drug is a novel fumarate that is similar to Biogen’s dimethyl fumarate, but it has a unique structure that rapidly converts to monomethyl fumarate in the body. As a result, the drug causes less gastrointestinal (GI) irritation; studies of dimethyl fumarate have revealed that GI adverse events (AEs), such as diarrhea, nausea, and abdominal pain, are among the most commonly reported, and often lead to discontinuation. For patients who do not tolerate dimethyl fumarate, today’s approval may provide a new option.

Data supporting approval of the new therapy come from the ongoing EVOLVE-MS program; EVOLVE-MS-1 enrolled 582 patients, 73% of whom had previously been treated for MS. Patients in the trial received diroximel fumarate at a dose of 462 mg twice daily for up to 96 weeks. Discontinuation due to GI AEs was 0.5%, and no GIs were deemed serious.

In the EVOLVE-MS-2 trial, a head-to-head study of GI tolerability, 506 patients were randomized 1:1 to oral treatment with diroximel fumarate or dimethyl fumarate for 5 weeks. GI symptoms were assessed using the Individual GI Symptom and Impact Scale (IGISIS) and the Global GI Symptom and Impact Scale. The study found that patients receiving the novel agent had fewer days of GI symptoms with intensity scores of 2 or higher on the IGISIS compared to patients who received dimethyl fumarate (P = .0003).

The overall proportion of patients who discontinued due to GI AEs during the 5 weeks of the study were 1.6% in the diroximel fumarate arm and 6.0% in the dimethyl fumarate arm.

“MS is a heterogeneous disease, and real-world patient circumstances can vary, reinforcing the benefits of having therapeutic choices to support the diverse range of treatment considerations,” said Robert Naismith, MD, professor of neurology, Washington University School of Medicine, in a statement announcing the drug’s approval. “Throughout its clinical development program, Vumerity has demonstrated a desirable therapeutic profile, making it a compelling new option for patients.”

Reference

Naismith R, Leigh-Pemberton R, Rezendes D, et al. EVOLVE-MS-1: a phase 3, open-label, long-term safety study of ALKS 8700 in relapsing-remitting multiple sclerosis (P6.360). Neurology. 2018;90(15). n.neurology.org/content/90/15_Supplement/P6.360.