Abstract Details

Title Safety and Clinical Efficacy Outcomes From the Long-term Extension Study of Tolebrutinib in Participants With Relapsing Multiple Sclerosis: 2.5-Year Results

Topic Multiple Sclerosis

Presentation(s) S16 - MS Clinical Trials and Therapeutics (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

Background Phase 2b trial findings showed brain-penetrant Bruton’s tyrosine kinase inhibitor tolebrutinib was well tolerated and elicited dose-dependent reductions in new gadolinium-enhancing T1 and new/enlarging T2 lesions in participants with relapsing multiple sclerosis.

Objective To report tolebrutinib’s safety and efficacy at Week 120 (2.5 years) in a Phase 2b trial (NCT03889639) long-term safety (LTS) extension (NCT03996291).

Design/Methods In LTS Part A, participants continued their core study tolebrutinib dose (5, 15, 30, or 60 mg/day) double-blind until Phase 3 study dose selection (60 mg/day). In Part B, participants received open-label tolebrutinib 60 mg/day. Safety was assessed via adverse events (AE). Efficacy outcomes included annualized relapse rate (ARR) and change in Expanded Disability Status Scale (EDSS) score from baseline.

Results In the LTS extension, 107 (85.6%) participants have ongoing treatment as of 7 July 2022. Reasons for treatment discontinuation were: perceived lack of efficacy (n=5), progressive disease (n=4), participant’s decision (n=3), AEs (n=3), immigration (n=2), and planned pregnancy (n=1). At LTS Week 120, no new safety signals have been observed. The most common treatment-emergent AEs (TEAEs) were COVID-19 (24.8% [31/125]), headache (13.6% [17/125]), nasopharyngitis (12.8% [16/125]), upper respiratory tract infection (11.2% [14/125]), cystitis bacterial, arthralgia and back pain (7.2% each [9/125]), and pharyngitis (6.4% [8/125]). There was no observed tolebrutinib dose effect for TEAEs or serious AEs in Part A and no safety signals emerged for participants switching to tolebrutinib 60 mg/day in Part B. For participants who received tolebrutinib 60 mg/day for ≥8 weeks (n=124), ARR was 0.20 (95% CI: 0.14, 0.28) and 73.4% remained relapse-free. Mean EDSS remained stable to Week 120.

Conclusions Through LTS Week 120, tolebrutinib 60 mg/day continues to demonstrate a favorable safety profile, and is associated with low ARR and stable disability.

Authors/Disclosures
Jiwon Oh, MD, FAAN (St Michael's Hospital) PRESENTER	Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen-Idec. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD-Serono. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics. Dr. Oh has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen-Idec. Dr. Oh 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. Oh has received research support from Biogen-Idec. The institution of Dr. Oh has received research support from Roche.
Sana Syed, MD (Sanofi Genzyme)	Dr. Syed has received personal compensation for serving as an employee of Sanofi US.
	No disclosure on file
Naji Salloum, MD (Sanofi)	Dr. Salloum has received personal compensation for serving as an employee of Sanofi. Dr. Salloum has received personal compensation for serving as an employee of Biogen. Dr. Salloum has stock in Biogen.
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.
Robert J. Fox, MD, FAAN (Cleveland Clinic)	Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AB Science. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Immunic. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for INmune Bio. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lily. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Biosciences. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Fox 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. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic. Dr. Fox 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. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AB Science. Dr. Fox 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. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. The institution of Dr. Fox has received research support from National Institutes of Health. The institution of Dr. Fox has received research support from National MS Society. Dr. Fox has received publishing royalties from a publication relating to health care.