Diroximel Fumarate Pregnancy Outcomes in EVOLVE-MS-1 and Study Design of Diroximel Fumarate Prospective MS Pregnancy Exposure Registry
Maria Houtchens1, Annette Wundes2, Benjamin Osborne3, Ivan Bozin4, Filipe Branco4, Hailu Chen4, Sarah England4, Nancy Gerber4, Seth Levin4, Xiaochen Lin4, Matthew Scaramozza4, Kerstin Hellwig5
1Brigham MS Center, 2University of Washington, 3Georgetown University Hospital, 4Biogen Inc., 5University of Bochum
Objective:
1. To report pregnancy outcomes from women with multiple sclerosis (MS) exposed to diroximel fumarate (DRF) during pregnancy in EVOLVE-MS-1. 2. To describe a prospective, international pregnancy registry of women with MS (BlossoMS).
Background:
DRF, a next-generation oral fumarate approved for relapsing forms of MS, has the same active metabolite, monomethyl fumarate, and fewer gastrointestinal AEs compared with dimethyl fumarate (DMF). While many patients with MS are women of childbearing potential, there are limited data on developmental risks associated with use of DRF before and during pregnancy.
Design/Methods:
1. EVOLVE-MS-1 (NCT02634307) is an open-label, 96-week study assessing DRF safety, tolerability, and efficacy. Any female found to be pregnant while participating in EVOLVE-MS-1 was discontinued from study treatment, but the pregnancy was followed until completion or termination. 2. BlossoMS, anticipated to begin in 2023, aims to evaluate effects of DRF on pregnancy outcomes and compare women with MS exposed to DRF with those exposed to other disease-modifying therapies (DMTs), unexposed to DMTs, and women without MS.
Results:
Overall, 9 patients in EVOLVE-MS-1 had pregnancies; median (range) age at enrollment was 28 (19–33, n=9) years, median (range) overall DRF exposure in EVOLVE-MS-1 was 306.5 (12–431, n=8) days, and median (range) duration of DRF exposure during pregnancy was 46 (29–101, n=6) days. Of 9 pregnancies, 6 outcomes were live birth without congenital abnormality, including one set of twins; 1 was an elective termination with no known fetal defects; and 2 were spontaneous abortion.
Conclusions:
We report pregnancy outcomes in women exposed to DRF during pregnancy. It is important to better understand potential pregnancy-related risks associated with use of DRF to help providers and patients with medical decision-making. The BlossoMS registry will provide essential information on the risk of birth defects, congenital abnormalities, and pregnancy outcomes among women with MS exposed to DRF during pregnancy.