Safety and Tolerability of Conversion to Siponimod in Patients with Relapsing Multiple Sclerosis: Interim Results of the EXCHANGE Study (4598)

Objective: To report interim results of EXCHANGE (NCT03623243), a 6-month, open-label, single-arm study evaluating safety/tolerability of converting to siponimod from other disease-modifying treatments (DMTs). Background: In the USA, siponimod is approved in adults for treatment of RMS, including active SPMS. Understanding washout requirements when converting from other DMTs to siponimod is important in clinical practice and should be assessed prospectively. Design/Methods: Analysis included patients aged 18–65 years with advancing RMS, EDSS 2.0–6.5, and on continuous oral/injectable DMTs for ≥3 months at time of consent. Patients were immediately converted to siponimod, except those previously on teriflunomide who required 11–14 days’ washout (with cholestyramine or activated charcoal). During days 1–6, siponimod was titrated from 0.25 to 2mg. Primary endpoint was drug-related adverse event (AE) incidence. About 100 patients are being enrolled in a parallel, novel virtual cohort, with telemedicine tools. Results: 112 patients (1 in virtual arm; 70.5% female) from 42 US centers were eligible for safety analysis (33.9% ongoing; 20.5% discontinued; 45.5% completed). At screening, 74.1% (n=83) had RRMS, 21.4% (n=24) had SPMS, 3.6% (n=4) had PPMS and 0.9% (n=1) had a single demyelinating event; 42.0% (n=47) had ≥1 relapse in prior 12 months. At baseline, median age was 45.5 years, median time since MS diagnosis was 11.2 years and median EDSS score was 3.5. In the safety analysis, ≥1 drug-related AE was reported in 34.8% of patients (n=39) (95% CI: 26.2–44.5); 4.5% (n=5) had ≥1 serious AE and 5.4% (n=6) had ≥1 AE leading to drug discontinuation. In patients who had completed/discontinued the study (n=74), 40.5% (n=30) (95% CI: 29.5–52.6) had ≥1 drug-related AE. Change from baseline in heart rate to 6 hours post-first dose and AEs by prior DMT will be presented. Conclusions: Conversion from oral/injectable DMTs to siponimod without washout had a good safety and tolerability profile with no unexpected findings. Disclosure: Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen/Actelion. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara Biotherapeutics. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech. The institution of Dr. Bar-Or has received research support from Merck/EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genetech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH. Dr. Mao-Draayer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen Idec. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme-Sanofi. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme-Sanofi. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Mao-Draayer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen Idec. The institution of Dr. Mao-Draayer has received research support from NIH . The institution of Dr. Mao-Draayer has received research support from Genzyme-Sanofi. The institution of Dr. Mao-Draayer has received research support from Novartis. The institution of Dr. Mao-Draayer has received research support from Genentech. Gina Cox has nothing to disclose. Linda-Ali Cruz has nothing to disclose. Dr. Meng has nothing to disclose. Wendy Su, PhD has nothing to disclose. Dr. Cohan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cohan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Cohan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Cohan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Cohan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb (Celgene). Dr. Cohan has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Cohan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for sanofi genzyme. Dr. Cohan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Dr. Cohan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche Genentech. Dr. Cohan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb.