Role of Diroximel Fumarate in Multiple Sclerosis

Fred Lublin, MD: Let’s move on to the diroximel fumarate, Patricia.

Patricia K. Coyle, MD: It’s a prodrug that has monomethyl fumarate, which is the active agent of dimethyl fumarate. It’s packaged differently. This was studied in EVOLVE-MS-2, which was a trial that entered about 506 patients with relapsing MS [multiple sclerosis]. It was only a 5-week trial. The patients were randomized to dimethyl fumarate 240 mg PO [by mouth] twice a day, or diroximel fumarate 462 mg twice a day, so that’s 2 capsules twice a day versus the 1 capsule twice a day. The primary outcome was gastrointestinal [GI] symptoms rated on a daily scale. They were significantly less with diroximel fumarate compared to dimethyl fumarate. The dropout rate due to [adverse] effects of GI was much less with diroximel fumarate. In other words, this is a differently packaged DMF [dimethylformamide] that significantly decreases the GI [adverse] effects of DMF, and you don’t need to take it with food. This has now been approved. It’s on the market here. Right now it’s being suggested that, if there was somebody who you would want to start on DMF but they had GI issues, you could consider using diroximel fumarate, or if somebody starts DMF and they have GI issues, you could switch them. It’s interesting.

Fred Lublin, MD: Is it available in Europe?

Wallace Brownlee, MBChB, PhD, FRACP: It’s not approved at the moment in the United Kingdom, but at least in my practice [at the National Hospital for Neurology and Neurosurgery], gastrointestinal disturbance is one of the main reasons that people discontinue dimethyl fumarate, at least in the first couple months of treatment. I see this as potentially being an attractive treatment option in patients who, as Patricia says, don’t tolerate dimethyl fumarate, or those who have irritable bowel syndrome or other gastrointestinal comorbidity, you may want to start this in preference to dimethyl fumarate.

Fred Lublin, MD: Sven?

Sven Meuth, MD, PhD: We also haven’t gotten approval yet, but it’s a very valuable option. I also don’t know why we continue on Tecfidera [dimethyl fumarate] if we can have it without the [adverse] effects.

Patricia K. Coyle, MD: Exactly.

Sven Meuth, MD, PhD: It’s hard to understand, but patients starting on Tecfidera without [adverse] effects are very happy with this drug. We do see a certain percentage of patients starting the drug, but they have to stop because of [adverse] effects. If we can now significantly reduce these [adverse] effects, that would be fantastic.