Evobrutinib Efficacy is Maintained Over Two Years in an Open-label Phase II Study Extension in Patients with Relapsing Multiple Sclerosis

Objective: To report long-term efficacy of evobrutinib in patients with relapsing multiple sclerosis over combined randomized and open-label extension (OLE) study periods. Background: Evobrutinib is a highly selective Bruton’s tyrosine kinase inhibitor with dual mode of action, targeting B cells and myeloid cells. Evobrutinib’s clinical efficacy in relapsing multiple sclerosis was shown in a Phase II, randomized, controlled trial NCT02975349: T1 Gd-enhancing lesions significantly decreased versus placebo at Week 24 (primary endpoint); efficacy continued through Week 48. Design/Methods: During the double-blind period (DBP), patients received evobrutinib 25mg QD, 75mg QD, 75mg BID, or placebo for 24 weeks, continuing treatment until 48 weeks, except the placebo group, who switched to 25mg QD. At Week 48, patients could enter the OLE. Treatment was evobrutinib 75mg QD (median ≈48 weeks), then 75mg BID. Efficacy was assessed by annualized relapse rate (ARR), and cumulative probability of and time to first qualified relapse (QR) in patients completing ≥60 weeks of OLE treatment or discontinuing. Results: Of 213 patients randomized in the DBP, 164 (77%) entered the OLE; of these, 148 (90%) completed ≥108 weeks in total. Compared with those initiated in other DBP arms, patients initiated on evobrutinib 75mg BID had: lower ARR (95% CI), 0.11 (0.04, 0.25) at Week 48 and 0.12 (0.06, 0.22) at Week 108; lower cumulative probability of first QR, 0.08 (0.00, 0.16) at Week 48 and 0.20 (0.08, 0.31) at Week 96. The estimated time by which 20% of patients had a QR was almost three times longer for those initiated on 75mg BID versus placebo. Conclusions: Improvement in ARR with evobrutinib 75mg BID at Week 48 was maintained at Week 108. Probability of and time to first QR highlighted that patients initiated on 75mg BID achieved greater treatment efficacy than those initiated on evobrutinib 25mg QD, 75mg QD, or placebo. Disclosure: The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck/ EMD Serono. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene/ Receptos. Dr. Montalban 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. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Nervgen. Dr. Montalban 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. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann-La Roche. Dr. Montalban 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. Montalban 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. The institution of Dr. Montalban has received research support from Abbvie. The institution of Dr. Montalban has received research support from Biogen. The institution of Dr. Montalban has received research support from Medday. The institution of Dr. Montalban has received research support from Hoffmann-La Roche. The institution of Dr. Montalban has received research support from Sanofi. The institution of Dr. Montalban has received research support from Merck. The institution of Dr. Montalban has received research support from Novartis. The institution of Dr. Montalban has received research support from Teva. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GENeuro. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Receptos/Celgene. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received stock or an ownership interest from NeuroRx. The institution of Dr. Arnold has received research support from Novartis. The institution of Dr. Arnold has received research support from Immunotec. Martin Weber, MD has nothing to disclose. Ivan Staikov has nothing to disclose. Karolina Piasecka-Stryczynska has nothing to disclose. Emily Martin has received personal compensation for serving as an employee of EMD Serono. Dr. Mandel has received personal compensation for serving as an employee of EMD Serono. Dr. Dangond has received personal compensation in the range of $1,000,000+ for serving as a Head, Global Clinical Development (employee for 12 years) with EMD Serono. Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alkermes. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GW Pharma. Dr. Wolinsky has received intellectual property interests from a discovery or technology relating to health care. Dr. Wolinsky has received intellectual property interests from a discovery or technology relating to health care. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving as a CME Lectures with AcademicCME. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving as a CME Lectures with Annenberg Center. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving as a CME Lectures with Consortium of MS Centers. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving as a CME Lectures with PRIME.