FDA Approves Diroximel Fumarate for Relapsing Forms of Multiple Sclerosis

Officials with the FDA have approved diroximel fumarate (Vumerity) for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive disease, according to a press release.

Diroximel fumarate is a novel oral fumarate with a distinct chemical structure that is designed to impact its gastrointestinal (GI) tolerability.

This approval is based on a New Drug Application (NDA) submitted under the 505(b)(2) filing pathway supported by data from studies comparing diroximel fumarate with dimethyl fumarate (Tecfidera) to establish bioequivalence, as well as interim exposure and safety findings. The approval relied in part on the FDA’s findings of safety and efficacy for dimethyl fumarate.

In the 5-week phase 3 EVOLVE-MS-2 study, diroximel fumarate was evaluated in comparison with dimethyl fumarate for GI tolerability. According to the findings, diroximel fumarate demonstrated statistical superiority to dimethyl fumarate on the study’s pre-specified primary endpoint, with patients treated with diroximel fumarate self-reporting significantly fewer days of key GI symptoms with intensity scores ≥2 on the Individual Gastrointestinal Symptom and Impact Scale compared with dimethyl fumarate.

The most common adverse effects reported in the study for both treatment groups were flushing, diarrhea, and nausea (32.8%, 15.4%, and 14.6% for diroximel fumarate; 40.6%, 22.3%, and 20.7% for dimethyl fumarate, respectively). The study also showed a low overall rate of diroximel fumarate treatment discontinuation due to adverse events (6.3%) and a rate of less than 1% of patients who discontinued treatment due to GI adverse events.

Additionally, exploratory efficacy endpoints in the ongoing EVOLVE-MS-1 study showed changes in clinical and radiological measures compared with baseline.

“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,” Robert Naismith, MD, professor of neurology at Washington University School of Medicine in St Louis, said in a statement. “Throughout its clinical development program, Vumerity has demonstrated a desirable therapeutic profile, making it a compelling new option for patients.”

Under the terms of the license and collaboration agreement between Biogen and Alkermes, Biogen will pay Alkermes $150 million in connection with the FDA’s approval of diroximel fumarate and royalties from commercial sales of the drug, according to the release.

References

Biogen and Alkermes Announce FDA Approval of Vumerity (Diroximel Fumarate) for Multiple Sclerosis [news release]. Biogen’s website. http://investors.biogen.com/news-releases/news-release-details/biogen-and-alkermes-announce-fda-approval-vumeritytm-diroximel. Accessed October 30, 2019.

Alkermes and Biogen Announce US Food and Drug Administration Acceptance of Diroximel Fumarate New Drug Application for Multiple Sclerosis [news release]. Biogen’s website. https://investors.biogen.com/news-releases/news-release-details/alkermes-and-biogen-announce-us-food-and-drug-administration. Accessed October 30, 2019.