Safety and Clinical Efficacy Outcomes From the Long-term Extension Study of Tolebrutinib in Participants With Relapsing Multiple Sclerosis: 2.5-Year Results
Jiwon Oh1, Sana Syed2, Tong Li3, Naji Salloum2, Timothy J. Turner2, Robert J. Fox4
1St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada, 2Sanofi, Cambridge, MA, USA, 3Sanofi, Bridgewater, NJ, USA, 4Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, USA
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).
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.
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.