Abstract Details

Title Diroximel Fumarate Pregnancy Outcomes in EVOLVE-MS-1 and Study Design of Diroximel Fumarate Prospective MS Pregnancy Exposure Registry

Topic Multiple Sclerosis

Presentation(s) P9 - Poster Session 9 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-003

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.

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).

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.

Authors/Disclosures
Maria K. Houtchens, MD PRESENTER	Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche . Dr. Houtchens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cravath. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Beasley . Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Biogen. The institution of Dr. Houtchens has received research support from Genzyme. The institution of Dr. Houtchens has received research support from Biogen. The institution of Dr. Houtchens has received research support from Genentech.
Annette Wundes, MD, FAAN (University of Washington)	The institution of Dr. Wundes has received research support from Benaroya Research Institute .
Benjamin J. Osborne, MD, FAAN (Medstar Georgetown University Hospital)	Dr. Osborne has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen. Dr. Osborne has received publishing royalties from a publication relating to health care.
Ivan Bozin (Biogen International GmbH)	Dr. Bozin has received personal compensation for serving as an employee of Biogen. Dr. Bozin has received personal compensation for serving as an employee of Arvelle Therapeutics. Dr. Bozin has stock in Biogen.
	No disclosure on file
	No disclosure on file
Sarah England, PhD (Biogen)	Dr. England has received personal compensation for serving as an employee of Biogen. Dr. England has stock in Biogen.
	No disclosure on file
Seth N. Levin, MD (Biogen)	Dr. Levin has received personal compensation for serving as an employee of Biogen. Dr. Levin has received stock or an ownership interest from Biogen.
	No disclosure on file
Matthew Scaramozza	Mr. Scaramozza has received personal compensation for serving as an employee of Biogen. Mr. Scaramozza has stock in Biogen. Mr. Scaramozza has received intellectual property interests from a discovery or technology relating to health care.
Kerstin Hellwig (St. Josef Hospital Bochum)	Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for INC research . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Kerstin Hellwig has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen . Kerstin Hellwig has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer . The institution of Kerstin Hellwig has received research support from Roche . The institution of Kerstin Hellwig has received research support from Merck . The institution of Kerstin Hellwig has received research support from Biogen. The institution of Kerstin Hellwig has received research support from Genzyme . The institution of Kerstin Hellwig has received research support from Novartis . The institution of Kerstin Hellwig has received research support from TEVA.