Abstract Details

Title Safety Profile Characterization of Evobrutinib in Over 1000 Patients from Phase II Clinical Trials in Multiple Sclerosis, Rheumatoid Arthritis and Systemic Lupus Erythematosus

Topic Multiple Sclerosis

Presentation(s) S14 - MS Therapeutics (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Background Evobrutinib, a highly selective oral Bruton’s tyrosine kinase inhibitor (BTKi), targets B cells, macrophages and microglia involved in autoimmunity.

Objective To analyze the safety profile, including class-related treatment-emergent adverse events (TEAEs), of evobrutinib using pooled data from phase II trials in MS, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

Design/Methods Data from three phase II, randomized, double-blind, placebo-controlled trials of evobrutinib were analyzed (MS: n=213, 48 weeks, NCT02975349; RA: n=390, 12 weeks, NCT03233230; SLE: n=480, 52 weeks, NCT02975336).

Results Data from 1083 patients were pooled (evobrutinib: n=861; placebo: n=271; 49 MS patients received both placebo [Week 0–24] and evobrutinib [Week 25–48]). The proportion of patients with TEAEs and the exposure-adjusted incidence rate (EAIR) was similar for evobrutinib and placebo (66.2% [247.6 events/100 pt-years] vs 62.4% [261.4 events/100 pt-years]). The EAIR of TEAEs (events/100 pt-years) for evobrutinib vs placebo were similar by indication: MS: 119.7 vs 148.3; RA: 331.8 vs 306.8; SLE: 342.9 vs 302.1. The proportion of Grade ≥3 or Grade ≥4 TEAEs with evobrutinib vs placebo was 11.8% vs 11.8% and 0.8% vs 0.7%, respectively. TEAEs reported in ≥5% of evobrutinib-treated patients were urinary tract infections (9.5% vs 8.5% placebo), nasopharyngitis (7.3% vs 5.5% placebo) and diarrhea (6.2% vs 4.8% placebo). The EAIR of transient elevated ALT and AST (events/100 pt-years) with evobrutinib vs placebo was 4.84 vs 2.76 and 3.48 vs 0.69, respectively. The EAIR of serious infections was 2.72 and 2.07 events/100 pt-years for evobrutinib and placebo, with no imbalance between evobrutinib doses. There were no serious infections with the highest evobrutinib dose in MS and RA; the EAIR in SLE was similar to placebo (50mg BID: 2.06 vs 2.00 events/100 pt-years).

Conclusions

These results represent the first BTKi integrated safety analysis including MS patients. Evobrutinib treatment was generally well tolerated across indications.

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.
	No disclosure on file
Daniel Wallace (Cedars-Sinai Medical Center)	No disclosure on file
	No disclosure on file
Davorka Tomic	Davorka Tomic has stock in Meck KGaA.
	No disclosure on file
	No disclosure on file
	No disclosure on file

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