Alkermes and Biogen have reported that diroximel fumarate demonstrated a statistically superior gastrointestinal (GI) tolerability profile compared to Tecfidera (dimethyl fumarate) in a Phase III EVOLVE-MS-2 study for relapsing-remitting multiple sclerosis (RRMS).
Diroximel fumarate is an investigational, oral fumarate candidate designed to convert to monomethyl fumarate in the body. It is intended for the treatment of RRMS.
The multi-centre, double-blind, active-controlled EVOLVE-MS-2 trial compared the GI tolerability profiles of 462mg twice daily diroximel fumarate and 240mg twice daily dimethyl fumarate over five weeks in a total of 506 participants.
Its primary endpoint was the number of days subjects reported GI symptoms with an intensity score of ≥2 on the IGISIS rating scale.
Performed twice daily, the IGISIS assessed the intensity of certain GI symptoms, such as nausea, vomiting, upper and lower abdominal pain, and diarrhoea. A ten on the scale is said to represent extreme intensity.
During the trial, subjects on the investigational drug self-reported significantly fewer days of GI symptoms with IGISIS intensity scores of ≥2, compared to dimethyl fumarate.
The most common adverse events in both treatment groups were flushing, diarrhoea, and nausea.
In the diroximel fumarate arm, 1.6% of all patients with AEs discontinued the study, versus 6% treated with dimethyl fumarate.
Of these discontinuations, 0.8% in the study drug group and 4.8% in the dimethyl fumarate group have been attributed to GI adverse events.
Alkermes medicines development and medical affairs chief medical officer and senior vice-president Craig Hopkinson said: “These results reinforce the safety and tolerability profile diroximel fumarate has consistently demonstrated across the EVOLVE-MS development programme, underscoring the potential importance of diroximel fumarate for the treatment of people living with relapsing-remitting MS.”
The EVOLVE-MS-2 study forms part of the EVOLVE-MS clinical programme, which is being conducted by Alkermes and Biogen under a global development and commercialisation deal.