Abstract Details

Title Immune Response Following COVID-19 Vaccination (mRNA or Non-mRNA) in Patients with Relapsing Multiple Sclerosis Treated with the Bruton’s Tyrosine Kinase Inhibitor Evobrutinib: An Update

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-017

Objective To examine the humoral response to mRNA and non-mRNA COVID-19 vaccination in patients with relapsing multiple sclerosis (PwRMS) receiving evobrutinib during the open-label extension (OLE) of a Phase II trial (NCT02975349).

Background Evobrutinib is a highly selective, central nervous system-penetrant, covalent Bruton’s tyrosine kinase inhibitor being investigated in RMS. A preliminary analysis showed that evobrutinib-treated PwRMS (n=24) could mount an antibody response to mRNA COVID-19 vaccines.

Design/Methods Post hoc analysis of PwRMS who received both evobrutinib 75mg twice-daily (fasted) and COVID-19 vaccines during the OLE (n=45; mRNA n=37, non-mRNA n=8; booster n=14). Immunoglobulin G (IgG) anti-S1/S2 (SARS-CoV-2 spike protein domains) specific COVID-19-antibodies were measured using an indirect chemiluminescence immunoassay (DiaSorin Molecular LLC, USA; lower limit of quantification, 3.8 AU/mL; seronegative <15.0 AU/mL, seropositive ≥15 AU/mL).

Results Baseline mean (SD) age of patients was 46.0 (9.6) years, 68.9% were female and mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks. Of 45 evobrutinib-treated patients, 43 developed or increased S1/S2 IgG antibody levels post-vaccination (geometric mean [SD] pre-/post-vaccination: mRNA 8.5 [4.3]/247.7 [4.5] AU/mL, non-mRNA 12.1 [3.2]/197.1 [6.2]). Patients who were either S1/S2 IgG seronegative (n=32) or seropositive (n=13) pre-vaccination demonstrated an antibody response following vaccination (seronegative pre-/post-vaccination geometric mean [SD]: 4.3 [1.3]/133.6 [3.7] AU/mL; seropositive pre-/post-vaccination: 55.5 [4.0]/984.4 [2.9]). Most patients (n=36/45), whether seronegative or positive, demonstrated a 10–100-fold increase of S1/S2 IgG antibody levels from pre- to post-vaccination (geometric mean [SD] fold change of S1/S2 IgG antibody levels for total/seronegative/seropositive patients: 26.4 [3.4]/31.0 [3.4]/17.7 [3.3]). S1/S2 IgG levels post-booster were higher versus post-vaccination.

Conclusions Prior data that evobrutinib-treated PwRMS mounted an antibody response to mRNA COVID-19 vaccination are supported further by this larger population analysis. These results provide additional evidence that evobrutinib-treated PwRMS can mount a humoral response to COVID-19 vaccinations and that, with boosters, antibody levels increase further than after the first vaccination cycle.

Authors/Disclosures
Elise Drouin, PhD (EMD Serono) PRESENTER	Dr. Drouin has received personal compensation for serving as an employee of EMD Serono. Dr. Drouin has stock in Agenus.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	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 Biogen. 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 as a Consultant for cabaletta. 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.
Anne H. Cross, MD, FAAN (Washington University School of Medicine)	Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech / F. Hoffman la Roche. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb . Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Cross 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. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Cross has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Consortium of MS Centers. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Cross has received research support from Genentech. Dr. Cross has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Yann Hyvert, PhD (Merck Healthcare KGaA)	Dr. Hyvert has received personal compensation for serving as an employee of The healthcare business of Merck KGaA, Darmstadt, Germany. An immediate family member of Dr. Hyvert has received personal compensation for serving as an employee of The healthcare business of Merck KGaA, Darmstadt, Germany.
	No disclosure on file
Nektaria Alexandri	Nektaria Alexandri has received personal compensation for serving as an employee of Merck Healthcare KGaA.
Davorka Tomic	Davorka Tomic has stock in Meck KGaA.
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia)	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.

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