MS Agent Diroximel Fumarate Shows Superior GI Safety in Phase 3

Craig Hopkinson, MD, chief medical officer, and senior vice president, medicines development and medical affairs, Alkermes

Craig Hopkinson, MD

Top-line results from the EVOLVE-MS-2 trial of diroximel fumarate, an investigational novel oral fumarate with a distinct chemical structure, suggest that it is superior to dimethyl fumarate (Tecfidera, Biogen) in that patients with relapsing multiple sclerosis (MS) experienced fewer days of key gastrointestinal (GI) symptoms with intensity scores ≥2 on the Individual Gastrointestinal Symptom and Impact Scale (IGISIS) compared to those on dimethyl fumarate (P =.0003), according to Alkermes and Biogen.¹

Results of the phase 3 randomized, double-blind, 5-week study were announced by Alkermes and Biogen.

The IGISIS was completed twice daily and evaluated the intensity of key GI symptoms, including nausea, vomiting, upper and lower abdominal pain, and diarrhea.

“Diroximel fumarate demonstrated statistically superior GI tolerability compared to dimethyl fumarate on the EVOLVE-MS-2 study’s primary endpoint, as well as a low discontinuation rate of less than 1% due to GI adverse events (AEs),” Craig Hopkinson, MD, chief medical officer, and senior vice president, medicines development and medical affairs, Alkermes, said in a statement. “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.”

Alkermes and Biogen stated that further analysis of the data from the EVOLVE-MS-2 study is ongoing and will be presented at a future scientific forum. Overall, the study included 506 patients with relapsing MS, in which they were assigned to either diroximel fumarate 462 mg twice daily or dimethyl fumarate 240 mg twice daily. The therapy is designed to rapidly convert to monomethyl fumarate in the body.

With regard to AEs, the most common for both groups were flushing (diroximel fumarate, 32.8%; dimethyl fumarate, 40.6%), diarrhea (diroximel fumarate, 15.4%; dimethyl fumarate, 22.3%), and nausea (diroximel fumarate, 14.6%; dimethyl fumarate, 20.7%). The investigational agent saw 1.6% of patients with AEs discontinue the study as a result, compared to 6.0% for dimethyl fumarate. GI AEs accounted for 0.8% for diroximel fumarate and 4.8% for dimethyl fumarate.

“With a chronic disease like MS, interrupting or stopping treatment due to GI side effects can often provoke the return of disease activity. Physicians and patients should work together to choose a medication that provides the right balance of efficacy, safety, and tolerability to help manage patients’ MS and meet their treatment goals,” said Robert Naismith, MD, professor of neurology, Washington University School of Medicine in St. Louis. “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.”

Hopkinson added that the companies are looking forward to the Q4 completion of its new drug application by the FDA. Biogen stated that it plans to market the treatment under the conditionally approved brand name Vumerity. In its submission to the FDA, diroximel fumarate is referencing dimethyl fumarate based on bioequivalence data.

The EVOLVE-MS diroximel fumarate clinical development program is being conducted as part of a worldwide development and commercialization agreement between Alkermes and Biogen.

“As part of our leadership in multiple sclerosis, Biogen has long understood that the disease differs from person to person, as well as throughout the course of the disease. We are committed to offering a range of options to patients to meet their needs,” said Michael Ehlers, executive vice president, research & development at Biogen. “These data build on the foundation we have created with Tecfidera, the most prescribed oral MS therapy worldwide, and further demonstrates the potential of diroximel fumarate as a novel oral fumarate within our MS portfolio.”

REFERENCE

Diroximel Fumarate Demonstrated Significantly Improved Gastrointestinal Tolerability Profile Compared to Dimethyl Fumarate in Patients with Multiple Sclerosis [press release]. Dublin, Ireland, and Cambridge, MA: Alkermes and Biogen; Published July 30, 2019. globenewswire.com/news-release/2019/07/30/1893560/0/en/Diroximel-Fumarate-Demonstrated-Significantly-Improved-Gastrointestinal-Tolerability-Profile-Compared-to-Dimethyl-Fumarate-in-Patients-with-Multiple-Sclerosis.html. Accessed August 1, 2019.