Vumerity (diroximel fumarate) is an approved oral treatment for multiple sclerosis (MS) that helps to reduce relapse rates and slow the development of brain lesions. It also may delay disability progression for people with MS.
The treatment was originally developed by Alkermes, which licensed it to Biogen in 2017.
Vumerity contains an inactive molecule called diroximel fumarate, which is converted into its active form, monomethyl fumarate (MMF), once inside the body.
The mechanism of action of MMF in MS patients remains incompletely understood. But broadly, the therapy is believed to reduce MS-driving inflammation by altering the activity of immune cells. It also is thought to have antioxidant properties that protect against neuronal damage.
MMF also is the active agent in Tecfidera (dimethyl fumarate), an older MS treatment also developed by Biogen. Vumerity delivers a comparable amount of MMF as Tecfidera, but has been shown to cause fewer gastrointestinal side effects.
The U.S. Food and Drug Administration (FDA) approved the medication in 2019 for the treatment of adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).
The European Commission approved Vumerity for use in the EU in 2021, but only for adults with RRMS.
Vumerity should not be given to people with a known allergy to diroximel fumarate, dimethyl fumarate, or any other ingredient in the medication. It also is not recommended for those already taking Tecfidera.
Vumerity is available as delayed-release hard capsules containing 231 mg of the inactive molecule diroximel fumarate. These capsules are white and are printed with “DRF 231 mg” in black ink on the body.
The recommended maintenance dose of the medication is 462 mg, taken as two oral capsules, twice a day, for a total of four capsules per day. However, during the first week of treatment, patients receive a smaller dosage of 231 mg twice daily.
The therapy can be taken with or without food, but high-fat or high-calorie meals should be avoided when taking Vumerity. Also, taking it with food or with aspirin may reduce the incidence and severity of flushing, or reddening of the skin, a common side effect of the medication.
Capsules should be swallowed whole, and not crushed, chewed, or sprinkled on food.
Vumerity’s regulatory approvals were supported by efficacy data from two Phase 3 trials of Tecfidera, DEFINE (NCT00420212) and CONFIRM (NCT00451451). In these trials, the active molecule dimethyl fumarate significantly lowered relapse rates, by about 50%, and reduced the number of new and enlarging brain lesions by more than 70%.
The approval packages also included data from Phase 1 and Phase 3 studies comparing the efficacy, safety, and distribution of Vumerity against Tecfidera in healthy volunteers and MS patients.
A randomized Phase 1 clinical trial (NCT02201849) initially compared Vumerity against Tecfidera and a placebo in 104 healthy volunteers. Results indicated that both medications delivered the same amount of the active ingredient MMF, but fewer patients on Vumerity reported gastrointestinal side effects.
Alkermes, in collaboration with Biogen, then began assessing the safety, tolerability, and effectiveness of Vumerity in two overlapping Phase 3 clinical trials. EVOLVE-MS-2 (NCT03093324) was completed in 2019, while EVOLVE-MS-1 (NCT02634307) wrapped up in 2021.
EVOLVE-MS-2 enrolled 506 people with RRMS who were randomly assigned to receive either Vumerity or Tecfidera, at the approved doses of 462 and 240 mg, twice daily for five weeks.
The trial’s primary goal was to determine the number of days participants reported gastrointestinal symptoms with a score of 2 or greater on the Individual Gastrointestinal Symptom and Impact Scale (IGISIS). That 11-point scale measures digestive symptoms including vomiting, diarrhea, and abdominal pain, with higher scores indicating worse symptoms.
As in the initial study, participants given Vumerity experienced fewer and less severe gastrointestinal side effects. Specifically, patients reported 46% fewer days with scores of 2 or greater on the IGISIS scale as compared with patients on Tecfidera.
These reductions in gastrointestinal symptoms were tied to improved quality of life and less missed work among people receiving Vumerity. Participants receiving the medication also had a lower rate of treatment discontinuation due to gastrointestinal side effects (4.8% vs. 0.8%).
Patients who completed the five-week treatment period in EVOLVE-MS-2, as well as people with RRMS who had not previously participated in any Vumerity clinical trial, were then able to join the EVOLVE-MS-1 open-label study. All participants in that study received 462 mg of the medication twice daily for 96 weeks.
EVOLVE-MS-1 enrolled 1,057 adults. Interim data involving 696 patients showed that the therapy significantly lowered relapse rates — by 79% — after one year, and reduced the number of brain lesions with active inflammation by 77%. The effects were particularly more profound in the group of patients who had been diagnosed in the previous year and had not received treatment. Importantly, after two years on Vumerity, more than 90% of patients had not experienced worsening disability.
Safety data in EVOLVE-MS-1 generally were positive: while 87% of participants reported side effects, the vast majority (90%) of such events were mild to moderate in severity. About a third of participants experienced gastrointestinal side effects, but less than 1% of those participants discontinued treatment because of them.
Additional findings from this trial also demonstrated that switching to Vumerity from previous disease modifying therapies, particularly glatiramer acetate (sold as Copaxone among others) and interferon-based medications, was safe and associated with reduced relapse rates and active brain lesions.
The most common side effects associated with Vumerity, based on data from Tecfidera clinical trials, include:
Patients on Vumerity may have an increased risk of viral infections, including those caused by herpes zoster, and other serious infections. If such an infection develops, treatment may be suspended until the infection resolves.
Progressive multifocal leukoencephalopathy or PML, a rare and serious form of brain infection caused by the John Cunningham virus, also may occur in patients receiving this medication. Vumerity must be immediately stopped at the first sign of PML.
Vumerity may lower the levels of certain white blood cells called lymphocytes. Blood cell counts should be assessed before starting on the medication and monitored regularly while on it.
Damage to the liver may occur during treatment. Liver function should be checked before starting Vumerity and regularly during treatment.
Patients on Vumerity may experience allergic reactions, including rash, swelling of the tongue and throat, and difficulty breathing. Patients who experience any signs of an allergic response should stop the medication and seek immediate medical care.
Adequate research into Vumerity use during pregnancy is lacking. However, animal studies suggest that the medication may cause harm to a developing fetus, increasing the risk of malformations, neurological impairments, and death.
It remains unknown if the medication can pass into breast milk. Patients who are or plan to become pregnant or breastfeed while receiving the therapy should discuss these topics with their healthcare providers.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Vumerity was approved by the U.S. Food and Drug Administration in October 2019 as a treatment for adults with relapsing forms of MS. These types include clinically isolated syndrome, relapsing-remitting multiple sclerosis, and active secondary progressive multiple sclerosis.
Based on animal studies, Vumerity use during pregnancy can cause harm to a developing fetus. Patients who become or plan to become pregnant while on the medication should discuss this issue with their healthcare provider.
Patients on Vumerity do not have to stop drinking alcohol completely, but they should not drink any at the same time they take the medication. This is because alcohol can reduce the amount of the medication’s active ingredient that is absorbed by the body. Patients should talk with their healthcare team to understand when and how much alcohol is safe for them to drink.
As each person reacts differently to a given treatment, there is no standard timeline for how soon Vumerity is expected to start working. Patients should ask their healthcare providers how the medication can help in their specific case.
While weight gain and hair loss were not reported in clinical trials as side effects of Vumerity, some patients who received the active ingredient after the medication’s approval have experienced hair loss. Patients who experience unanticipated effects of treatment should discuss these with their healthcare team.
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