Safety and Clinical Efficacy Outcomes From the Long-term Extension Study of Tolebrutinib in Patients With Relapsing Multiple Sclerosis:18-Month Results

ABSTRACT

Objective: To describe safety and efficacy of tolebrutinib in patients with relapsing multiple sclerosis at Week 72 (Month 18) in the long-term safety (LTS) extension of the phase 2b trial. Background: In the phase 2b trial (NCT03889639), tolebrutinib, a CNS-penetrant Bruton's tyrosine kinase inhibitor, was well tolerated over 12 weeks with dose-dependent reduction in new gadolinium-enhancing T1 and new/enlarging T2 lesions. Design/Methods: The LTS extension (NCT03996291) consists of 2 parts patients continued their core study tolebrutinib dose (5, 15, 30, or 60 mg/day) double-blind until the phase 3 study dose was selected (Part A), and currently receive tolebrutinib 60 mg/day open-label (Part B). Long-term safety and tolerability is the primary objective. Secondary endpoints include annualized relapse rate (ARR) and change from baseline in Expanded Disability Status Scale (EDSS) score. Results: 124 of 125 patients treated in the extension completed Part A and transitioned to Part B. One patient (on 5 mg/day) discontinued Part A due to progressive disease and 6 discontinued Part B due to a variety of reasons, including adverse event (AE;n=2), lack of efficacy (n=1), progressive disease (n=1), and emigration (n=2). To date, no new safety signals have been observed. The most common treatment-emergent AEs (TEAEs) were headache (12.8% [16/125]), COVID-19 (12.8% [16/125]), nasopharyngitis (10.4% [13/125]), upper respiratory tract infection (8.0% [10/125]), and arthralgia (5.6% [7/125]). There was no suggestion of a dose effect for TEAE or serious AE in Part A and no emergence of new safety signals for patients switching to 60 mg in Part B. ARR on tolebrutinib 60 mg was 0.17 (95% CI 0.11, 0.27);84.7% of patients were relapse-free at the LTS Week 72 cut-off. Mean EDSS scores remained stable to LTS Week 72. Conclusions: Through LTS Week 72, tolebrutinib 60 mg continues to show favorable safety and tolerability, and low ARR.