Abstract Details

Title Safety and Efficacy of Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor in Relapsing Multiple Sclerosis Over 2.5 Years of The Open-Label Extension to a Phase II Trial

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-001

Objective Report the safety and efficacy of evobrutinib over 2.5 years in an open-label extension (OLE).

Background Evobrutinib, a covalent, blood-brain barrier-penetrating Bruton’s tyrosine kinase inhibitor, was well tolerated and effective at reducing gadolinium-enhancing lesions in a double-blind, randomized phase II trial in patients with relapsing multiple sclerosis (pwRMS; NCT02975349).

Design/Methods In the 48-week (W) double-blind period (DBP), pwRMS (n=267) received placebo (switched to evobrutinib 25mg once-daily at W24), evobrutinib 25mg once-daily, 75mg once-daily, or 75mg twice-daily, or open-label dimethyl fumarate (DMF; 240mg twice-daily). At W48 patients could enter the OLE (DMF: 4–8W washout); evobrutinib 75mg once-daily (median ~48W) then 75mg twice-daily. The latest available OLE data are now reported.

Results Of 267 DBP patients, 213 (80%) entered the OLE; 164 (61%) completed ≥132W of OLE treatment. Treatment-emergent adverse events (TEAEs) were reported by 165/213 patients (77.5%); 59 (27.7%) had a treatment-related TEAE. Six serious TEAEs were deemed treatment-related. Severe/opportunistic infections (≥Grade 3) were reported by 9/213 patients (4.2%); 3 were fatal (Covid-19 pneumonia [n=2] and E. coli sepsis [n=1]; not considered treatment-related). At OLE W120, most patients had IgG (91%), IgA (88%) and IgM (82%) within normal ranges. Overall mean CD19+ B cells levels were 0.218x10⁶ cells/mL (OLE baseline) and 0.122x10⁶ cells/mL (OLE W96). ALT/AST elevations were observed only in patients previously receiving DMF/evobrutinib 25mg and occurred within 12W of OLE initiation. Amylase/lipase increases occurred in 6 (2.8%)/24 (11.3%) patients, but without clinical signs and symptoms. Based on all available OLE data, ARR was 0.12 (95%CI 0.07–0.20) for patients receiving 75mg twice-daily in the DBP.

Conclusions Evobrutinib safety and efficacy data over 2.5 years in pwRMS continue to show acceptable tolerability, with no new safety signals, and maintained efficacy.

Authors/Disclosures
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia) PRESENTER	The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck/ EMD Serono. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 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 Teva. 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. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BMS/ Celgene. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/ Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIAL PD. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerVoice. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung Biosys. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas BioPharma. 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 Actelion/ Janssen Pharmaceuticals. 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 $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS/ Celgene. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 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 $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 $500-$4,999 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 $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of 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 Immunic Therapeutics. The institution of 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 Viatris/ Mylan. The institution of 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 Sandoz. The institution of Dr. Montalban has received research support from Biogen. The institution of Dr. Montalban has received research support from Hoffmann-La Roche. The institution of Dr. Montalban has received research support from Sanofi/ Genzyme. The institution of Dr. Montalban has received research support from Merck/ EMD Serono. The institution of Dr. Montalban has received research support from Novartis. The institution of Dr. Montalban has received research support from Teva Pharmaceuticals. The institution of Dr. Montalban has received research support from Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received research support from BMS/ Celgene.
Jerry S. Wolinsky, MD, FAAN (McGovern Medical School, UTHealth)	Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avotres. Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Brainstorm Cell Therapeutics. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cleveland Clinic Foundation. Dr. Wolinsky 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. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inmagene. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis/Sandoz. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Alabama Birmingham. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. 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.
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. 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 $5,000-$9,999 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 $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 personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clario.
	No disclosure on file
Ivan Staikov	Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Sanofi. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ewopharma-Biogen. Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Shire. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gedeon-Richter. Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Teva. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boehringer Ingelheim. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Polpharma. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Penumbra. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Adapt. Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Merck. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerot Lannach. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medochemie. Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nobel Pharma.
Karolina Piasecka-Stryczynska	Karolina Piasecka-Stryczynska has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Karolina Piasecka-Stryczynska has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Karolina Piasecka-Stryczynska has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi.
Davorka Tomic	Davorka Tomic has stock in Meck KGaA.
Emily C. Martin	Emily Martin has received personal compensation for serving as an employee of EMD Serono.
Kristina Holmberg, PhD (EMD Serono)	Dr. Holmberg has received stock or an ownership interest from Merck KGaA.
	No disclosure on file

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