Improved Gastrointestinal Tolerability Profile with Diroximel Fumarate Compared to Dimethyl Fumarate in Relapsing MS Patients (994)

Objective: To evaluate tolerability and impact of gastrointestinal (GI) adverse events (AEs) with diroximel fumarate (DRF) versus dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (MS). Background: DRF is an investigational, oral fumarate for relapsing forms of MS with an improved GI tolerability profile compared to DMF. DRF 462 mg and DMF 240 mg produce bioequivalent exposure of the active metabolite monomethyl fumarate. Well-tolerated treatment options may lower treatment burden for patients. Design/Methods: EVOLVE-MS-2 (NCT03093324) is a randomized, double-blind study evaluating GI tolerability of twice-daily DRF 462 mg and DMF 240 mg. Patient-assessed GI symptoms were evaluated using two scales: Individual Gastrointestinal Symptom and Impact Scale (IGISIS) and Global Gastrointestinal Symptom and Impact Scale (GGISIS). Interference and burden of GI symptoms were explored. Results: Among patients with ≥1 post-baseline self-assessment of GI tolerability (n=502), fewer DRF- versus DMF-treated patients characterized their GI events as interfering with regular daily activities “quite a bit” and “extremely”: nausea (2.4% vs 6.8%), vomiting (1.2% vs 5.6%), upper abdominal pain (1.2% vs 6.8%), lower abdominal pain (1.2% vs 3.2%), and diarrhea (3.6% vs 6.4%). DRF-compared to DMF-treated patients were less likely to have an IGISIS score ≥2 for ≥2 consecutive days (17.4% vs 29.3%; risk ratio 0.59 [95% CI, 0.43–0.83]). Fewer DRF-treated patients reported concomitant medications for GI tolerability (17/88 [19.3%]) compared to DMF (37/121 [30.6%]). Among patients receiving ≥1 dose of study drug (n=504), GI AEs were lower with DRF than DMF (88/253 [34.8%] vs 123/251 [49.0%]).Treatment discontinuation due to GI AEs was lower for DRF versus DMF (0.8% vs 4.8%). Conclusions: GI symptoms interfered less with daily activities for DRF-treated patients compared to DMF. Further benefits on additional measures of treatment burden, including lower medication use for GI symptoms, were seen with DRF. GI AEs leading to discontinuation were Support: Biogen/Alkermes Disclosure: Dr. Wundes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Compensation as an advisor from Biogen. Dr. Wundes has received research support from Research support from Biogen, Alkermes, AbbVie.Dr. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received compensation for consulting, scientific advisory boards, or other activities with Alkermes, Actelion, Acorda Therapeutics, Celgene, EMD Serono, GeNeuro, GW Pharma, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanof. Dr. Wolinsky has received royalty, license fees, or contractual rights payments from Royalties are received for out-licensed monoclonal antibodies through UTHealth from Millipore Corporation.Dr. Wray has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting, principal investigator, and/or speaking fees (Alkermes, Biogen, Celgene, EMD Serono, Genentech/Roche, Novartis, Sanofi Genzyme, and TG Therapeutics).. Dr. Wray has received research support from Consulting, principal investigator, and/or speaking fees (Alkermes, Biogen, Celgene, EMD Serono, Genentech/Roche, Novartis, Sanofi Genzyme, and TG Therapeutics).. Consulting and/or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva) grant/research support (Biogen, Novartis, Sanofi, and Teva)Dr. Jasinska has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Allergan, Hoffman La-Roche, Teva, Adamed, and Polfarma. Dr. Freedman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer Healthcare, Biogen Idec, Chugai, Clene Nanomedicine, EMD Serono Canada, Genzyme, Merck Serono, Novartis, F. Hoffmann-La Roche Ltd, Sanofi-Aventis and Teva Canada Innovation. Dr. Freedman has received compensation for serving on the Board of Directors of Actelion, Bayer Healthcare, Biogen Idec, Clene Nanomedicine, F. Hoffmann-La Roche Ltd, Merck Serono, MedDay Pharmaceuticals, Novartis and Sanofi-Aventis. Dr. Freedman has received research support from Genzyme Canada. Dr. Bidollari has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes. Dr. Bidollari holds stock and/or stock options in Alkermes which sponsored research in which Dr. Bidollari was involved as an investigator.Dr. Chen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Biogen. Dr. Chen holds stock and/or stock options as a Full-time employee of Biogen and holds stock/stock options in Biogen which sponsored research in which Dr. Chen was involved as an investigator. Dr. Chen holds stock and/or stock options in options in Biogen. Dr. Hanna has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Hanna holds stock and/or stock options in Biogen which sponsored research in which Dr. Hanna was involved as an investigator. Dr. Leigh-Pemberton has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Alkermes. Dr. Leigh-Pemberton holds stock and/or stock options in Full-time employee of and holds stock/stock options in Alkermes which sponsored research in which Dr. Leigh-Pemberton was involved as an investigator. Dr. Leigh-Pemberton holds stock and/or stock options in Full-time employee of and holds stock/stock options in Alkermes.. Dr. Lyons has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Biogen. Dr. Lyons holds stock and/or stock options in Full-time employee of and holds stock/stock options in Biogen which sponsored research in which Dr. Lyons was involved as an investigator. Dr. Messer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Biogen. Dr. Messer holds stock and/or stock options in Full-time employee of and holds stock/stock options in Biogen which sponsored research in which Dr. Messer was involved as an investigator. Dr. Naismith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Alkermes, Biogen, Celgene, EMD Serono, Genentech, Genzyme, Novartis, TG Therapeutics, Viela Bio. Dr. Naismith has received personal compensation in an editorial capacity for Associate Editor, NEJM Journal Watch.