The U.S. Food and Drug Administration (FDA) accepted a new drug application for Vumerity in February 2019.
How Vumerity works
Multiple sclerosis is a progressive neurodegenerative disease where the immune system mistakenly attacks the myelin sheath, a protective coating that surrounds the nerve fibers. This causes nerve cells to become fragile and easily damaged, which interferes with the transmission of nerve signals from the brain to the rest of the body and vice versa.
Vumerity contains a small molecule called diroximel fumarate, which is a prodrug, meaning that it is not, by itself, active. Once ingested, however, diroximel fumarate is converted into its active form monomethyl fumarate (MMF).
While MMF’s exact mechanism of action is not clearly understood, it is known to change the profile of immune cells in the body, shifting the immune system away from a pro-inflammatory state. This is thought to prevent the attack on the nervous system.
MMF is also thought to have antioxidant properties — meaning that it reduces the levels of toxic molecules called reactive oxygen species (ROS). These ROS molecules are known to increase the activity of immune cells, as well as themselves, and thereby cause damage to nerve cells in MS patients.
Vumerity in clinical trials
A Phase 1, randomized, double-blind, placebo-controlled clinical trial (NCT02201849), conducted in 2015, assessed the safety, tolerability, and pharmacokinetics (movement in the body) of a single dose of either Vumerity or Tecfidera in 35 healthy volunteers. Participants then received the other treatment for the remainder of the study, which allowed crossover comparison of the two treatments. The most common adverse effects were flushing, dizziness, and constipation with Vumerity, and flushing, nausea, and diarrhea with Tecfidera.
Alkermes is currently assessing the safety and effectiveness of Vumerity in two Phase 3 studies in patients with relapsing-remitting multiple sclerosis (RRMS) — the EVOLVE-MS-1 trial (NCT02634307) and the EVOLVE-MS-2 trial (NCT03093324).
EVOLVE-MS-1 is a two-year, open-label study to investigate the long-term safety of Vumerity in an estimated 935 patients with RRMS, at 107 sites across the U.S and Europe. The trial is expected to finish in December 2020.
Interim trial results were presented at the 2018 American Academy of Neurology Annual Meeting. The analysis of the first 570 patients showed an annualized relapse rate (ARR) of 0.16 after one year of treatment. Of these patients, 152 were also assessed by magnetic resonance imaging (MRI) scans for changes in the number and size of lesions in the brain of patients compared to the start of the study. The scans showed a significant reduction in lesions.
Additional interim data were presented at the 2019 Consortium of Multiple Sclerosis Centers. For newly diagnosed patients, the ARR decreased by 83% from baseline following one year of Vumerity treatment. In addition, the number of lesions visible by MRI was reduced by 96% after 48 weeks of treatment. For patients who had been treated previously, ARR decreased by 72%, and lesion number was reduced by 64% after 48 weeks of treatment with Vumerity.
EVOLVE-MS-2 is a head-to-head study comparing the gastrointestinal tolerability of 462 mg of Vumerity taken twice daily, and 240 mg of Tecfidera taken twice daily. This five-week study will involve around 420 people with RRMS at 65 sites in the U.S. and Poland. It will compare the intensity, frequency, and duration of common gastrointestinal symptoms, including nausea, vomiting, upper and lower abdominal pain, and diarrhea. The study is still recruiting participants and is expected to be completed in February 2020.
Vumerity was originally developed by Alkermes and was licensed to Biogen in 2017. Biogen will have the exclusive worldwide rights to commercialize Vumerity, should the therapy be approved by the FDA and other regulatory agencies.
MMF is also the active metabolite of Tecfidera, Biogen’s approved oral therapy for relapsing forms of MS. Tecfidera and Vumerity have a similar mechanism of action.
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