Results from the phase 3 EVOLVE-MS-2 study demonstrate superior tolerability for now-approved diroximel fumarate compared to dimethyl fumarate.
Alfred Sandrock Jr, MD, PhD
Results from the phase 3 EVOLVE-MS-2 study of diroximel fumarate (Vumerity; Biogen) demonstrate improved gastrointestinal (GI) tolerability in patients with multiple sclerosis (MS) compared to dimethyl fumarate (Tecfidera). Full study results will be presented at the 27th Annual Meeting of the European Charcot Foundation in Italy this week.
The multi-center, double-blind, active-controlled study evaluated GI tolerability of diroximel fumarate compared to dimethyl fumarate in 506 patients with relapsing-remitting MS (RRMS) across a 5-week period. Patients were assessed on GI tolerability measures including duration and severity as well as self-reporting on the Individual Gastrointestinal Symptom and Impact Scale (IGISIS), which assesses measures such as vomiting, nausea, upper and lower abdominal pain, and diarrhea.
The primary endpoint of the study was the number of days with reported GI symptoms with a symptom intensity score of >2 based on the IGISIS. The number of days where reported GI symptoms were graded with scores of ≥1 or ≥3 was counted as secondary endpoints.
Data showed that patients who received diroximel fumarate saw 46% fewer days with intensity scores of >2 on the IGISIS compared to dimethyl fumarate (adjusted rate ratio 0.54; 95% CI, 0.39-0.75, P = .0003). Diroximel fumarate reduced IGISIS intensity scores of >1 and >3 by 29% and 44%, respectively. Notably, the worst IGISIS scores declined over the 5-week treatment period.
The Global Gastrointestinal Symptom and Impact Scale (GGISIS) was used to assess the impact of GI symptoms on a patient’s daily activities. There was a 30% decrease in self-reported intensity scores of >1 on the GGISIS, as well as a reduction in days with scores of >2 and >3.
The incidence of GI-related AEs was 34.8% in the diroximel fumarate group compared to 49% in the dimethyl fumarate group. Overall, 78.3% and 83.7% of patients experienced general AEs in the diroximel fumarate and dimethyl fumarate groups, respectively. Discontinuations due to GI AEs were reported in 0.8% of patients in the diroximel fumarate group and 4.8% of patients in the dimethyl fumarate group.
“Tecfidera is a clinically meaningful treatment for patients, and we believe Vumerity now builds upon our franchise as another compelling option for relapsing MS,” Alfred Sandrock, Jr., MD, PhD, executive vice president of Research and Development and chief medical officer at Biogen, said in a statement.
After receiving FDA approval on October 30, Biogen has announced that diroximel fumarate is now available in the US for relapsing forms of MS. Additionally, patients who completed the 5-week treatment program are eligible to enroll in EVOLVE-MS-1, an open-label, safety study conducted over 96-weeks.
Biogen presents data demonstrating improved gastrointestinal tolerability with Vumerity (diroximel fumarate) compared to Tecfidera (dimethyl fumarate)[news release]. Cambridge, MA: Biogen. November 22, 2019. investors.biogen.com/news-releases/news-release-details/biogen-presents-data-demonstrating-improved-gastrointestinal. Accessed November 22, 2019.