Abstract Details

Title Interim Safety and Efficacy Outcomes in Patients With Relapsing-Remitting Multiple Sclerosis who Received Diroximel Fumarate for Up to 2 Years

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 075

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%.

Authors/Disclosures
Sibyl E. Wray, MD (Hope Neurology) PRESENTER	Dr. Wray has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Wray has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Wray has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb/Celgene. Dr. Wray has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Wray has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Wray has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Wray has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. Dr. Wray has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Wray has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Wray has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for EMD Serono. Dr. Wray has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Roche/Genentech. Dr. Wray has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi/Genzyme. The institution of Dr. Wray has received research support from Biogen. The institution of Dr. Wray has received research support from Atara Biotherapeutics. The institution of Dr. Wray has received research support from Bristol Myers Squibb/Celgene. The institution of Dr. Wray has received research support from Novartis. The institution of Dr. Wray has received research support from Roche/Genentech. The institution of Dr. Wray has received research support from Sanofi/Genzyme. The institution of Dr. Wray has received research support from TG Therapeutics. The institution of Dr. Wray has received research support from EMD Serono. The institution of Dr. Wray has received research support from Pharmaceuticals Corp..
Barry A. Singer, MD	Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Singer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Singer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Singer has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for TG Therapeutics. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myers Squibb (Celgene). Dr. Singer has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for EMD Serono. Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Singer has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Novartis. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Vanda. An immediate family member of Dr. Singer has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for TG Therapeutics. The institution of Dr. Singer has received research support from Novartis. The institution of Dr. Singer has received research support from Sanofi. The institution of Dr. Singer has received research support from TG Therapeutics. The institution of Dr. Singer has received research support from Bristol Myers Squibb.
	No disclosure on file
	No disclosure on file
Jerome Hanna	No disclosure on file
Jennifer Lyons, MD (Brigham and Women's Hospital)	Dr. Lyons has received personal compensation for serving as an employee of Biogen. Dr. Lyons has received stock or an ownership interest from Biogen.
Florian Then Bergh, MD (University of Leipzig, Klinik u. Poliklinik fuer Neurologie)	Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Actelion. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Fresenius. Dr. Then Bergh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda. The institution of Dr. Then Bergh has received research support from Actelion. The institution of Dr. Then Bergh has received research support from Novartis. The institution of Dr. Then Bergh has received research support from DFG (German Science Fund). The institution of Dr. Then Bergh has received research support from Fresenius. The institution of Dr. Then Bergh has received research support from Diamed. Dr. Then Bergh has received personal compensation in the range of $10,000-$49,999 for serving as a Member of the Institutional Ethics Board with University of Leipzig, Medical Faculty.
	No disclosure on file
Donald Negroski, MD (Negroski Neurology)	Dr. Negroski has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for biogen. Dr. Negroski has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for EMD. Dr. Negroski has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for gennetech. Dr. Negroski has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Negroski has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for novartis. Dr. Negroski has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for alexion. Dr. Negroski has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for jansen. Dr. Negroski has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for bms. The institution of Dr. Negroski has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Banner Life Science. The institution of Dr. Negroski has received research support from biogen. The institution of Dr. Negroski has received research support from sanofi/genzyme. The institution of Dr. Negroski has received research support from adamas. The institution of Dr. Negroski has received research support from alkermes. The institution of Dr. Negroski has received research support from EMD. The institution of Dr. Negroski has received research support from Novartis.

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