Vumerity™ (diroximel fumarate)
Experimental Medications: New S1P Receptor Modulators
Company: Alkermes plc and Biogen Inc.
- Oral medication being studied at 462 mg twice daily
- Being studied in RMS
Diroximel fumarate is in the same class of MS therapy as Biogen’s Tecfidera® (dimethyl fumarate), but is believed to cause fewer gastrointestinal (GI) side effects – such as diarrhea, nausea, vomiting, and abdominal pain – than Tecfidera. The exact mechanism of action by which diroximel fumarate exerts therapeutic effect in MS is not completely understood. However, upon entering the body, the medication is rapidly converted into the molecule monomethyl fumarate. The converted molecule is thought to activate an antioxidant protein that reduces oxidative stress, which in turn slows damage to protective nerve fibers in the brain.4
The FDA in February accepted a New Drug Application (NDA) from Biogen and Irelandbased Alkermes plc, seeking approval of diroximel fumarate for treatment of relapsing forms of MS (RMS). The FDA, which under federal law has six to 10 months to rule on an NDA, is expected to decide in late 2019 whether to approve the agent for RMS.4
The ongoing open-label EVOLVE-MS-1 trial is assessing the safety/tolerability and efficacy of diroximel fumarate over 96 weeks in 503 individuals with RMS. Those study subjects include both newly diagnosed patients (people who were diagnosed with MS less than one year before study entry and who have not had a prior disease-modifying therapy [DMT]) and those with more long-standing RMS. All participants in the Phase III trial receive diroximel fumarate 462 mg twice daily.
Interim results from the Phase III study were reported at the American Academy of Neurology’s 2019 Annual Meeting, held in Philadelphia in May. Data covering 48 weeks of treatment showed that relapse rates fell approximately 80 percent among the entire study group relative to baseline. In addition, the number of gadolinium-enhancing lesions seen on MRI was reduced by 77% from baseline for the entire group and by 96% from baseline for the individuals who were newly diagnosed.72
Meanwhile, the five-week EVOLVE-MS-2 study, which is comparing the GI tolerability of diroximel fumarate with that of its kindred medication, dimethyl fumarate (Tecfidera), was scheduled for completion in June 2019.73 During this Phase III, double-blind trial, approximately 420 patients with RMS are being randomized in a 1:1 ratio to receive twice-daily doses of diroximel fumarate 462 mg or dimethyl fumarate 240 mg. Investigators are measuring the incidence, intensity, onset, duration, and functional impact of medication-related nausea, vomiting, upper or lower abdominal pain, and diarrhea. Their goal is to show that diroximel fumarate is better tolerated than dimethyl fumarate while offering comparable efficacy.74