Abstract Details

Title Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: NEDA-3 after Re-baselining in the Phase 3 EVOLVE-MS-1 Study

Topic Multiple Sclerosis

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-001

Background NEDA, a composite endpoint of clinical and MRI outcomes, is increasingly evaluated in multiple sclerosis (MS) studies. However, carry-over disease activity, before achieving the full effect of a disease-modifying therapy, may confound NEDA outcomes. Previous analyses with DRF and dimethyl fumarate (DMF), oral fumarates for relapsing MS, showed significant reductions in MRI activity as early as 7 weeks after initiation.

Objective To assess No Evidence of Disease Activity (NEDA) in patients on diroximel fumarate (DRF).

Design/Methods Patients with relapsing-remitting MS (aged 18-65 years) completing EVOLVE-MS-2 (NCT03093324), a randomized, blinded, 5-week, phase 3 study of DRF or DMF could continue into EVOLVE-MS-1 (NCT02634307), an open-label, 96-week study assessing DRF safety, tolerability, and efficacy. Relapses, Expanded Disability Status Scale scores, and MRI parameters were assessed during screening or on Day 1 of each study (~7 weeks apart). In this analysis, patients who had received DRF in both studies were re-baselined after ~7 weeks’ DRF treatment, and NEDA-3 was assessed over 96 weeks.

Results Overall, 239 patients received DRF in EVOLVE-MS-2 and entered EVOLVE-MS-1. Mean (standard deviation) age was 44.0 (11.0) years; 69.0% (n=165) were female. Over 96 weeks, the estimated proportion of patients who achieved NEDA-3 was 50.2%. Most patients (84.1%) were relapse-free on DRF over 96 weeks. An estimated 92.4% of patients were free of 24-week confirmed disability progression; 90.2% had no gadolinium-enhancing lesions; and 79.2% were free of new/newly-enlarging T2 lesions during the full study. Treatment-emergent adverse events occurred in 212 (88.7%) patients; 23 (9.6%) patients discontinued DRF due to adverse events.

Conclusions At Week 96, 50.2% of patients on DRF achieved NEDA-3 after re-baselining. Safety outcomes were consistent with those previously reported for EVOLVE-MS-1; discontinuations due to adverse events were low. Re-baselining may be useful for assessing DRF efficacy by mitigating the influence of disease activity prior to the onset of efficacy.

Authors/Disclosures
James D. Bowen, MD (Swedish Neuroscience Institute) PRESENTER	Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen IDEC. Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for BristolMyers Squibb. Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Bowen has received research support from Biogen IDEC. The institution of Dr. Bowen has received research support from Genentech. The institution of Dr. Bowen has received research support from Genzyme. The institution of Dr. Bowen has received research support from Novartis. The institution of Dr. Bowen has received research support from Roche.
Jessica Stulc, MD (Minneapolis Clinic of Neurology)	Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD serono . Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD serono . Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genentech. Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Stulc has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi . The institution of Dr. Stulc has received research support from EMD serono . The institution of Dr. Stulc has received research support from Novartis . The institution of Dr. Stulc has received research support from Sanofi . The institution of Dr. Stulc has received research support from Genentech. The institution of Dr. Stulc has received research support from Biogen.
Samuel F. Hunter, MD, PhD (Advanced Neurosciences Institute)	The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbview. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMDSerono. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. The institution of Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Osmotica. Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Hunter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Hunter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMDSerono. Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Hunter has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Hunter has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Hunter has received research support from Biogen. The institution of Dr. Hunter has received research support from Abbvie. The institution of Dr. Hunter has received research support from Genentech/Roche. The institution of Dr. Hunter has received research support from Janssen. The institution of Dr. Hunter has received research support from Novartis. The institution of Dr. Hunter has received research support from Osmotica. The institution of Dr. Hunter has received research support from Sanofi. Dr. Hunter has received intellectual property interests from a discovery or technology relating to health care. Dr. Hunter has received personal compensation in the range of $5,000-$9,999 for serving as a Speaker with MS Views and News. Dr. Hunter has a non-compensated relationship as a CEO - Volunteer with NeuroNexes/Novel Pharmaceutics Institute that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing support with Novartis Pharmaceuticals that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing Support with Osmotica that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing support with Mallinckrodt that is relevant to AAN interests or activities. Dr. Hunter has a non-compensated relationship as a Writing Support with Sanofi that is relevant to AAN interests or activities.
Ariel Antezana, MD (NeuroMedical clinic of cenla)	Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS. Dr. Antezana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen.
	No disclosure on file
James B. Lewin, PharmD	Dr. Lewin has received personal compensation for serving as an employee of Biogen. Dr. Lewin has stock in Biogen.
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.
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.
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. 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). 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.