Abstract Details

Title Efficacy and Safety of the Bruton’s Tyrosine Kinase Inhibitor Evobrutinib for Relapsing Multiple Sclerosis Over 3.5 Years of Treatment: An Ongoing Phase II Open-Label Extension

Topic Multiple Sclerosis

Presentation(s) S16 - MS Clinical Trials and Therapeutics (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Background Evobrutinib is a highly selective, central nervous system-penetrant, covalent Bruton’s tyrosine kinase inhibitor. In the Phase II trial, the efficacy (relapses and disability) and safety profile of evobrutinib observed in the double-blind period (DBP) were maintained over 2.5 years of the OLE.

Objective To report the long-term effect of evobrutinib on efficacy and safety in patients with relapsing multiple sclerosis (PwRMS) over 3.5 years of the open-label extension (OLE) of a Phase II trial (NCT02975349).

Design/Methods During the 48-week (W) DBP, PwRMS (n=267) received placebo (switched to evobrutinib 25mg once-daily [QD] after W24), evobrutinib 25mg QD, 75mg QD, 75mg twice-daily (BID), or open-label dimethyl fumarate (120mg BID for the first week, 240mg BID thereafter). All doses were administered fasted. At W48, patients could enter the OLE and received evobrutinib 75mg QD (mean [±SD] duration 49.8W [±6.2]) and then switched to 75mg BID. Data are reported from W48/OLE baseline to either 228W of treatment (annualized relapse rate [ARR]) or ≥228W of treatment (treatment-emergent adverse events [TEAEs]).

Results Of 213 patients who entered the OLE, 155 (72.8%) completed ≥228W of treatment. During the OLE, the pooled ARR was reduced with the post-switch evobrutinib 75mg BID dose (0.10) compared with the pre-switch 75mg QD dose (0.18). Overall, the pooled ARR remained low during the OLE up to W228 (0.13). TEAEs were reported by 178/213 patients (83.6%); 60/213 (28.2%) reported treatment-related TEAEs, 7/213 (3.3%) reported serious treatment-related TEAEs. Severe/opportunistic infections (≥Grade 3) were reported by 11/213 patients (5.2%).

Conclusions The pre- and post-switch ARR data support that BID dosing (75mg fasted, comparable to 45mg BID fed in Phase III) provides maximal efficacy on clinical endpoints. Evobrutinib, over 3.5 years in the OLE, continues to show maintained treatment benefits and acceptable tolerability, with no new safety signals.

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. 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. 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. 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. 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 stock in NeuroRx.
	No disclosure on file
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.
	No disclosure on file
	No disclosure on file