Better GI Tolerability With Diroximel vs Dimethyl Fumarate in MS

Megan Brooks

August 06, 2019

The investigational drug diroximel fumarate (Vumerity, Biogen/Alkermes) showed statistically superior gastrointestinal (GI) tolerability compared with dimethyl fumarate (Tecfidera, Biogen) in patients with relapsing-remitting multiple sclerosis (RRMS) in the EVOLVE-MS-2 trial, according to topline results released by Biogen/Alkermes.

"These results reinforce the safety and tolerability profile diroximel fumarate has consistently demonstrated across the EVOLVE-MS development program, underscoring the potential importance of diroximel fumarate for the treatment of people living with relapsing-remitting MS," Craig Hopkinson, MD, chief medical officer and senior vice president of medicines development and medical affairs at Alkermes, said in a news release.

Diroximel fumarate is similar to dimethyl fumarate in efficacy but has a unique chemical structure that may induce less irritation to the GI tract, the companies note.

EVOLVE-MS-2 was a phase 3, multicenter, double-blind, active-controlled, 5-week study evaluating GI tolerability of diroximel fumarate (462 mg twice daily) compared to dimethyl fumarate (240 mg twice daily) in 506 patients with RRMS.

The EVOLVE-MS-2 study achieved its primary endpoint, with patients taking diroximel fumarate experiencing statistically significantly fewer days of GI symptoms with a symptom intensity score of 2 or greater on the Individual Gastrointestinal Symptom and Impact Scale (IGISIS) compared with dimethyl fumarate (P = .0003). 

The overall incidence of investigator-reported GI adverse events, as well as the rate of treatment discontinuation as a result of these side effects, was low, the statement said.

The most common adverse events (AEs) reported in the study for both treatment groups were flushing, diarrhea, and nausea (32.8%, 15.4%, and 14.6%, respectively, for diroximel fumarate; 40.6%, 22.3%, and 20.7%, repsectively, for dimethyl fumarate).

The overall proportion of patients with AEs leading to study discontinuation was 1.6% for diroximel fumarate and 6.0% for dimethyl fumarate. Of those, the proportion of patients who discontinued due to GI adverse events during the treatment period was 0.8% for diroximel fumarate and 4.8% for dimethyl fumarate.

Further analysis of the data from the EVOLVE-MS-2 study is ongoing and will be presented at a future scientific forum, the release notes.

"With a chronic disease like MS, interrupting or stopping treatment due to GI side effects can often provoke the return of disease activity. These topline results suggest that diroximel fumarate offers a differentiated GI tolerability profile and may represent an important new option for people living with relapsing MS," Robert Naismith, MD, professor of neurology, Washington University School of Medicine, St. Louis, Missouri, said in the news release.

Diroximel fumarate is currently under review with the US Food and Drug Administration (FDA) with a target action date in the fourth quarter of 2019.  

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