Oral Vumerity Easier on Gastrointestinal Tract Than Tecfidera, Phase 3 Trial Finds

Fewer and less severe gastrointestinal (GI) side effects were evident in relapsing-remitting multiple sclerosis (RRMS) patients taking the investigational oral treatment Vumerity (diroximel fumarate) twice a day compared to those using Tecfidera (dimethyl fumarate), topline data from the EVOLVE-MS-2 trial show.

Vumerity is a fumarate compound being developed by Alkermes in collaboration with Biogen, the manufacturer of Tecfidera, for relapsing forms of MS.

“Diroximel fumarate demonstrated statistically superior GI tolerability compared to dimethyl fumarate … as well as a low discontinuation rate of less than 1% due to GI adverse events,” Craig Hopkinson, chief medical officer and senior vice president of medicines development and medical affairs at Alkermes, said in a press release. “These results reinforce the safety and tolerability profile diroximel fumarate has consistently demonstrated across the EVOLVE-MS development program.”

Alkermes is assessing its safety and effectiveness in two Phase 3 studies in patients with RRMS — the EVOLVE-MS-1 trial (NCT02634307), and the EVOLVE-MS-2 trial (NCT03093324).

Biogen recently announced trial data showing that Vumerity significantly reduces disease activity in RRMS patients, and with low rates of GI side effects.

Now, Alkermes presented data from EVOLVE-MS-2 trial that further bolsters Vumerity’s better GI safety profile compared to Tecfidera.

EVOLVE-MS-2 was a multicenter, double-blind, five-week study comparing the gastrointestinal tolerability of 462 milligram (mg) capsules of Vumerity, twice a day, compared to Tecfidera 240 mg  capsules twice daily. The study involved 506 RRMS patients, and took place at multiple sites in the U.S., Germany, and Poland. 

Results found that patients taking Vumerity reported fewer days of gastrointestinal side effects with intensity scores of 2 or higher on the IGISIS (Individual Gastrointestinal Symptom and Impact Scale). This scale was completed twice daily to evaluate the intensity of key GI symptoms, including nausea, vomiting, upper and lower abdominal pain, and diarrhea, on a rating scale that spans 0 (not at all) to 10 (extreme).

The most common side effects in both treatment groups were flushing (32.8% for those using Vumerity; 40.6% for those on Tecfidera), diarrhea (15.4% Vumerity; 22.3% Tecfidera), and nausea (14.6% Vumerity; 20.7% Tecfidera).

Importantly, compared to Tecfidera, fewer patients on Vumerity discontinued treatment due to adverse events — 1.6% versus 6.0%. This difference was also evident among those who stopped treatment specifically due to GI side effects: 0.8% in Vumerity group and 4.8% in the Tecfidera group.

“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, a professor at 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,” Naismith added.

Further analysis of the study’s data is underway and will be presented at a future meeting, Alkermes said in the release.

Vumerity is currently under review by the U.S. Food and Drug Administration (FDA), with a decision expected toward the end of 2019. If approved, the compound may offer RRMS patients a new treatment choice with lower gastrointestinal toxicity.

“We look forward to the FDA’s completion of its review of the diroximel fumarate NDA in the fourth quarter,” Hopkinson said. 

Vumerity (previously BIIB098 and ALKS8700) contains a small molecule called diroximel fumarate that is a prodrug, meaning that it is not, by itself, active. Once ingested, diroximel fumarate is converted into its active form monomethyl fumarate (MMF).

While MMF’s exact mechanism of action is not clear, it is thought to change the profile of immune cells in the body, shifting the immune system away from a pro-inflammatory state to prevent the neuroinflammation and damage to nerve cells seen in MS.