Abstract Details

Title Neurofilament Light Chain Levels and Disease Activity During Long-Term Treatment of Relapsing Multiple Sclerosis with the Bruton's Tyrosine Kinase Inhibitor Evobrutinib

Topic Multiple Sclerosis

Presentation(s) P1 - Poster Session 1 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-011

Objective To evaluate neurofilament light chain (NfL) levels, a biomarker of neuroaxonal damage, as a prognostic and a potential surrogate marker of evobrutinib treatment response (MRI and relapse outcomes) in patients with relapsing multiple sclerosis (PwRMS).

Background Evobrutinib is a highly selective, CNS-penetrant Bruton’s tyrosine kinase inhibitor, currently in Phase III for RMS. The efficacy of evobrutinib (MRI and clinical outcomes) observed in double blind phase (DBP) of a Phase II trial (NCT02975349) in PwRMS was maintained in the open-label extension (OLE; beginning at Week [W] 48 from DBP baseline). Previous analyses of the Phase II trial showed sustained reductions in NfL levels with evobrutinib up to W144.

Design/Methods NfL levels were measured over time in the pooled OLE safety population and reported as control-adjusted NfL Z-scores (expression of standard deviations [SDs] away from mean NfL level in a control population [participants without evidence of CNS disease]). The number of T1 Gd+ and new/emerging T2 lesions at W96 and W144 and qualified relapses over W96-144 were assessed, stratified by W96 NfL Z-scores (<1; ≥1 [Z-score 1 being one SD above the control mean]). MRI outcomes at W48 and W96 and relapses over W48-96 were also assessed using stratified W48 NfL Z-scores [<1; ≥1].

Results Stratified by W96 Z-scores (<1[N=66]; ≥1[N=34]), the proportion of patients with no T1 Gd+ lesions, no new/enlarging T2 lesions (both at W144) and no relapse between W96-144 were 84.5% (n=49/58) vs 57.1% (n=16/28), 65.5% (n=38/58) vs 28.6% (n=8/28) and 95.4% (n=62/65) vs 94.1% (n=32/34), respectively. Similar findings were observed in patients stratified by W48 Z-scores (<1[N=84]; ≥1[N=40]).

Conclusions Evobrutinib reduced NfL levels in a sustained manner (up to W144). Low NfL levels were associated with improved MRI and relapse outcomes, supporting the role of NfL as a prognostic marker of disease activity and a potential surrogate marker for evobrutinib’s treatment effect.

Authors/Disclosures
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel) PRESENTER	Dr. Kappos has nothing to disclose.
Jens Kuhle, MD	Dr. Kuhle has nothing to disclose.
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.
Pascal Benkert	Pascal Benkert has nothing to disclose.
Ying Li (EMD Serono)	Ying Li has received personal compensation for serving as an employee of EMD Serono.
	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.
Davorka Tomic	Davorka Tomic has stock in Meck KGaA.

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