Abstract Details

Title MRI Outcomes from the Long-term Extension Study of Tolebrutinib in Patients with Relapsing Multiple Sclerosis: 18-Month Results

Topic Multiple Sclerosis

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 326

Objective Report MRI outcomes at Week (W)72 (Month 18) in the long-term safety (LTS) extension of the phase 2b tolebrutinib trial in patients with relapsing multiple sclerosis.

Background In the phase 2b trial double-blind phase (DBP; NCT03889639), the CNS-penetrant Bruton’s tyrosine kinase inhibitor tolebrutinib was well tolerated over 12 weeks with dose-dependent reduction in new gadolinium (Gd)-enhancing T1 and new/enlarging T2 lesions.

Design/Methods After a variable treatment gap (0-21 weeks) following the last DBP tolebrutinib dose, patients began Part A of the extension (NCT03996291), in which they received their DBP dose (5, 15, 30, or 60 mg/day) double-blind until phase 3 study dose was selected. Currently, in extension Part B, patients receive 60 mg/day open-label. MRI outcomes include Gd-enhancing and new/enlarging T2 lesions, slowly evolving lesions (SEL), and paramagnetic rim lesions (PRL).

Results 124 of 125 patients treated in the extension completed Part A and transitioned to Part B; 118 (94%) remain on study as of 18 August 2021 (18-month cut-off). Numbers of new Gd-enhancing lesions remained low in the 60/60-mg arm through W72 and were reduced in other arms at W48 and W72 (mean±SD at W72: 0.62±1.06, 0.68±0.98, 0.86±2.42, 0.47±1.33 in 5/60-, 15/60-, 30/60-, 60/60-mg arms, respectively). New/enlarging T2 lesion counts remained low for 60/60 mg through W24, increasing slightly at W48 and W72. T2 lesion volume change remained low for 60/60 mg (W72 vs. baseline [mean±SD]: +0.39 ± 1.99 cm³). Median (IQR) W72 SEL volume was 441 (69-630), 468 (102-1317), 675 (150-1230), and 283.5 (168-504) mm³ for 5/60-, 15/60-, 30/60-, and 60/60-mg, respectively. PRL count remained unchanged in most patients.

Conclusions New Gd-enhancing lesion counts remained low for tolebrutinib 60/60 mg and were reduced in lower dose arms by LTS W48/72 when all patients had switched to 60 mg. Median W72 SEL volume was lowest with 60/60 mg.

Authors/Disclosures
Daniel Reich, MD, PhD (National Institutes of Health, Neuroimmunology Branch, NINDS) PRESENTER	Dr. Reich has received research support from NIH. The institution of Dr. Reich has received research support from Adelson Medical Research Foundation. The institution of Dr. Reich has received research support from Sanofi. The institution of Dr. Reich has received research support from Abata Therapeutics. The institution of Dr. Reich has received research support from National Multiple Sclerosis Society. The institution of Dr. Reich has received research support from Cure Alzheimer's Fund. Dr. Reich has received intellectual property interests from a discovery or technology relating to health care. Dr. Reich has received personal compensation in the range of $5,000-$9,999 for serving as a CME Faculty with Integrity. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with Letters and Sciences. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with Academic CME. Dr. Reich has a non-compensated relationship as a Advisor with Sanofi that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Board of Directors with ACTRIMS that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Abata Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with University of Basel RC2NB that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Multiple Sclerosis Society of Canada that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Tuscan Doctorate in Neuroscience that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Editorial Board with Multiple Sclerosis Journal that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Hyperfine that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Imaginab that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Annexon that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Philips that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Siemens that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Calico Life Sciences that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Cognito Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Sudo that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Allumis that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with BioCentury that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Regeneron that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Eli Lilly that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with SetPoint that is relevant to AAN interests or activities.
Anthony Traboulsee, MD (University of British Columbia)	Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Traboulsee has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Traboulsee has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Dr. Traboulsee has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. The institution of Dr. Traboulsee has received research support from Roche. The institution of Dr. Traboulsee has received research support from Consortium of MS Centers. The institution of Dr. Traboulsee has received research support from MS Canada. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Workshop Chair with Consortium of MS Centers.
Sana Syed, MD (Sanofi Genzyme)	Dr. Syed has received personal compensation for serving as an employee of Sanofi US.
Deborah Dukovic	No disclosure on file
Timothy J. Turner	Timothy J. Turner has received personal compensation for serving as an employee of Sanofi. Timothy J. Turner has stock in Sanofi. Timothy J. Turner 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.

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