Vumerity (diroximel fumarate) is a new oral treatment approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis (MS). It has been developed by Alkermes in collaboration with Biogen, and is available as delayed-release capsules.
The FDA’s October 2019 decision approving Alkermes’ new drug application was based in part on data from the pivotal Phase 3 EVOLVE-1 clinical trial (NCT02634307). That study, still ongoing in the U.S. and Europe, showed the long-term safety and effectiveness of the therapy, given twice daily, in patients with RRMS.
How does Vumerity work?
MS is a progressive neurodegenerative disease in which the immune system mistakenly attacks the myelin sheath, a protective protein coat that surrounds nerve fibers. This damages the nerve cells and interferes with the transmission of nerve signals from the brain to the rest of the body and back.
Vumerity (previously BIIB098 and ALKS8700) is made of a small molecule called diroximel fumarate, which is an inactive prodrug that is converted into its active form, monomethyl fumarate (MMF), inside the body.
While MMF’s exact mechanism of action is not clearly understood, evidence suggests that it activates a protein called Nrf2, which decreases inflammation by reducing the levels of toxic molecules called reactive oxygen species (ROS) inside cells. Therefore, Vumerity should reduce damage to the nerve cells and slow down the progression of MS.
Vumerity in clinical trials
A Phase 1, randomized, double-blind, placebo-controlled clinical trial (NCT02201849) assessed the safety, tolerability, and pharmacokinetics — movement in the body — of Vumerity in 104 healthy volunteers. The trial also evaluated Tecfidera, another approved MS medication with a similar mechanism of action.
A single dose of Vumerity between 49 mg and 980 mg or Tecifidera at 240 mg was give to participants. All doses of Vumerity were well-tolerated. The participants then took part in a crossover comparison of the two treatments. Vumerity had better pharmacokinetics compared with Tecifidera. Moreover, only 4.3% of participants who received Vumerity reported gastrointestinal issues compared with 41.7% of those who received Tecifidera. The most common adverse effects with Vumerity were flushing, dizziness, and constipation; with Tecfidera, they were flushing, nausea, and diarrhea.
Alkermes, in collaboration with Biogen, then began assessing the safety, tolerability, and effectiveness of Vumerity in two Phase 3 clinical trials in patients with relapsing-remitting multiple sclerosis (RRMS). These were the EVOLVE-MS-1 trial and the EVOLVE-MS-2 trial (NCT03093324).