Diroximel fumarate has been approved as a treatment for relapsing remitting multiple sclerosis (MS). It is taken as a tablet twice daily.
Diroximel fumarate for relapsing remitting MS: Appraisal
- 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 flushing, dizziness, and constipation. In clinical studies, diroximel fumarate caused fewer gastrointestinal side effects than Tecfidera.
The Medicines and Healthcare products Regulatory Agency (MHRA) has granted a licence for diroximel fumarate in England, Scotland and Wales for people with relapsing remitting multiple sclerosis.
The European Commission has also granted a licence. The EC licence covers Northern Ireland.
Diroximel fumarate is similar to Tecfidera (chemical name dimethyl fumarate). In the body, both drugs are converted to monomethyl fumarate.
In common with Tecfidera, the way diroximel fumarate works is not fully understood, but laboratory studies suggest that it may work in two ways:
reduces the inflammation caused when the immune system attacks myelin, resulting in less damage to myelin
protects nerve cells from damage caused by chemicals released during the immune attack
Diroximel fumarate is taken as two tablets, twice daily.
A phase I study in 35 people without MS indicated that diroximel fumarate had a very similar biological activity to Tecfidera.
EVOLVE-MS-1 - diroximel fumarate
This open-label (ie participants knew they were taking diroximel fumarate) phase III study evaluated the safety and tolerability of diroximel fumarate, taken for approximately 2 years, in more than 1000 participants with relapsing remitting MS. The main purpose of the study was to monitor side effects.
Interim results from 696 participants have been published. After one year of treatment with diroximel fumarate, the annualized relapse rate was 0.16 (down from 0.78 in the previous year). MRI results showed a significant reduction in the number of active MS lesions, compared to when they first joined the trial. Diroximel fumarate was well tolerated, with 6.3% stopping 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 recruited 504 participants with relapsing remitting MS who took either diroximel fumarate or Tecfidera for 5 weeks in order to compare gastrointestinal side effects. Participants completed daily questionnaires to assess gastrointestinal symptoms and their impact on daily activities and work. People taking diroximel fumarate experienced fewer days of gastrointestinal symptoms, took less medication for gastrointestinal symptoms and missed less work compared to Tecfidera. The overall proportion of participants stopping treatment because of side effects was 1.6% for diroximel fumarate and 5.6% for Tecfidera. Those who stopped treatment because of gastrointestinal problems was 0.8% for diroximel fumarate and 4.8% for Tecfidera.
The main side effects reported for diroximel fumarate were gastrointestinal discomfort which was mild to moderate in approximately 30% of participants and severe in 1% and flushing or flushing-related side effects which affected 44% of participants. Flushing side effects improved in 74% of those affected, on average within 3-4 days.
Other side effects included:
- chest infections.