Interim Safety and Efficacy Outcomes in Patients With Relapsing-Remitting Multiple Sclerosis who Received Diroximel Fumarate for Up to 2 Years
Sibyl Wray1, Barry A Singer2, Jelena Drulovic3, Hailu Chen4, Jerome Hanna4, Jennifer Lyons4, Florian Then Bergh5, Shivani Kapadia4, Donald Negroski6
1Hope Neurology MS Center, 2The MS Center for Innovations in Care, Missouri Baptist Medical Center, 3Clinic of Neurology, University of Belgrade, 4Biogen, 5Department of Neurology, University of Leipzig, 6MS Center of Sarasota
Objective:

 To report interim safety, tolerability, and efficacy outcomes in patients from EVOLVE-MS-1 who received diroximel fumarate (DRF) for ≤2 years.

Background:

DRF is an oral fumarate for relapsing multiple sclerosis (MS). DRF has the same pharmacologically active metabolite as dimethyl fumarate (DMF) and is expected to have a similar efficacy/safety profile. DRF has improved gastrointestinal (GI) tolerability versus DMF.

Design/Methods:
EVOLVE-MS-1 (NCT02634307) is an ongoing, open-label, 96-week study assessing DRF safety, tolerability, and exploratory efficacy endpoints in adults with relapsing-remitting MS. Patients who completed or discontinued treatment with an absolute lymphocyte count (ALC) <0.8x109 cells/L entered a lymphocyte monitoring period for ≤6 months. Efficacy assessments included the overall population, newly diagnosed (≤1 year since diagnosis, treatment naïve), and patients most recently treated with interferon or glatiramer acetate (IFN/GA switch).
Results:
As of 2 July 2019, 1051 patients were enrolled; median DRF exposure was 1.5 (range 0.0-2.0) years. Overall, 17.3% of patients discontinued treatment; 6.3% due to AEs and 0.7% due to GI AEs. AEs occurred in 82.1% (863/1051) of patients; 90% (779/863) were mild/moderate in severity. GI AEs occurred in 28.4% (299/1051) of patients. Mean ALC declined 28.7% over the first year and then stabilized (values x109 cells/L: baseline 1.81 [n=1041]; Wk48 1.29 [n=725]; Wk96 1.30 [n=472]). Seven (<1%) patients discontinued due to lymphopenia. Thirty-six patients entered the post-DRF lymphocyte monitoring period; median reconstitution time to an ALC >0.8x109 cells/L was 9.7 (range 7.6-36.9) weeks. On-treatment adjusted annualized relapse rate for the overall, newly diagnosed, and IFN/GA switch populations were 0.14 (95%CI 0.12-0.17), 0.13 (95%CI 0.07-0.22), and 0.15 (95%CI 0.11-0.20), respectively; estimated proportion who were relapse-free at Wk96 was 81.6%, 84.5%, and 81.7%, respectively. 
Conclusions:

Safety and efficacy results from the EVOLVE-MS-1 study were consistent with previous findings of DRF and the known benefit-risk profile for DMF. The rate of GI-related discontinuations was <1%.