Other names: BIIB098, Vumerity
Diroximel fumarate is a new drug treatment under investigation for relapsing remitting multiple sclerosis (MS). It is taken as a tablet twice daily.
Diroximel fumarate for relapsing remitting MS: Licensing
- Diroximel fumarate has biological activity similar to Tecfidera. In the body, both drugs are converted to monomethyl fumarate which reduces inflammation caused by MS activity and may protect nerve cells from damage.
- In relapsing remitting MS, diroximel fumarate reduced relapse rates and improved MRI measures of MS activity.
- In healthy participants, the most common side effects were were flushing, dizziness, and constipation. It is predicted that diroximel fumarate will have fewer gastrointestinal side effects than Tecfidera.
Licensing and appraisal
An application for a licence to market diroximel fumarate as a treatment for relapsing remitting MS has been submitted to the European Medicines Agency (Jan 2021).
How does diroximel fumarate work?
Diroximel fumarate is similar to Tecfidera (chemical name dimethyl fumarate). In the body, both drugs are converted to monomethyl fumarate. It is predicted that diroximel fumarate will cause fewer gastrointestinal side effects.
In common with Tecfidera, the way diroximel fumarate works is not fully understood, but laboratory studies suggest that it may work in two ways:
How is diroximel fumarate taken?
Diroximel fumarate is taken as a tablet, twice daily.
Diroximel fumarate research
What are the results so far?
A phase I study in 35 people without MS indicated that diroximel fumarate had a very similar biological activity to Tecfidera.
What further research is planned?
EVOLVE-MS-1 - diroximel fumarate
This phase III study is evaluating the safety and tolerability of diroximel fumarate, taken for approximately 2 years, in 935 participants with relapsing remitting MS. The main purpose of the study is to record the level of side effects.
Estimated completion date December 2020.
Further details of the study.
Interim results from 696 participants have been published. After one year of treatment with diroximel fumarate, the annualized relapse rate was 0.16. MRI results showed an improvement in measures of MS activity, compared to when they first joined the trial. Diroximel fumarate was well tolerated, with 6.3% discontinuing treatment because of side effects, of which less than 1% were due to gastrointestinal side effects. The most common side effects were flushing (affecting approximately 44%) and gastrointestinal discomfort (approximately 31%).
EVOLVE-MS-2 - diroximel fumarate compared to Tecfidera (dimethyl fumarate)
This phase III study is recruiting 500 participants with relapsing remitting MS who will take either diroximel fumarate or Tecfidera for 5 weeks in order to compare gastrointestinal side effects. The main measure will be the number of days that participants experience gastrointestinal symptoms.
Estimated completion date June 2019.
Further details of the study.
In a press release, the manufacturer reported results from this study. People taking diroximel fumarate experienced fewer days of gastrointestinal symptoms compared to Tecfidera. The overall proportion of participants stopping treatment because of side effects was 1.6% for diroximel fumarate and 6.0% for Tecfidera. Those who stopped treatment because of gastrointestinal problems was 0.8% for diroximel fumarate and 4.8% for Tecfidera.
It is proposed that diroximel fumarate will have fewer gastrointestinal side effects than Tecfidera.
In the phase I study the most common adverse effects were flushing, dizziness, and constipation.
- Neurology 2018; 90 (15 Supplement): P6.360. Summary EVOLVE-MS-1: A Phase 3, Open-Label, Long-Term Safety Study of ALKS 8700 in Relapsing-Remitting Multiple Sclerosis (P6.360)
- Neurology 2018; 90 (15 Supplement): P1.403 Summary Relative Bioavailability of Monomethyl Fumarate after Administration of ALKS 8700 and Dimethyl Fumarate in Healthy Subjects (P1.403).
- Multiple Sclerosis Journal 2020;26(13):1729-1739. Full article Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study
- CNS Drugs. 2020;34(2):185-196. Full article Diroximel fumarate demonstrates an improved gastrointestinal tolerability profile compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: results from the randomized, double-blind, phase III EVOLVE-MS-2 study.
- Adv Ther. 2019;36(11):3154–65. Full paper Improving the gastrointestinal tolerability of fumaric acid esters: early findings on gastrointestinal events with diroximel fumarate in patients with relapsing-remitting multiple sclerosis from the phase 3, open-label EVOLVE-MS-1 study.
Drugs in development
New MS medications can take years in development until they reach us. Find out about new drugs on the horizon for MS.
Drug development process
Find out about the different stages involved in making a new medicine.