Efficacy and Safety of Tolebrutinib in Patients With Highly Active Relapsing MS: Subgroup Analysis of the Phase 2b Study
Sana Syed1, Nicole Yonkers1, Christopher LaGanke2, William David Honeycutt3, Anthony Traboulsee4, Daniel Wynn5, Sibyl Wray6, Erik Wallstroem1, Deborah Dukovic1, Timothy Turner1
1Sanofi, 2North Central Neurology Associates, 3Neurology Associates, 4University of British Columbia, 5Consultants in Neurology MS Center, 6Hope Neurology
Objective:
Describe efficacy and safety in patients with relapsing MS (RMS) who had highly active disease (HAD) at baseline in the phase 2b trial of tolebrutinib (NCT03889639).
Background:
Tolebrutinib is a covalent, irreversible, central nervous system (CNS)–penetrant Bruton’s tyrosine kinase inhibitor targeting B lymphocytes and myeloid cells (eg, macrophages and microglia), modulating immunity in the periphery and CNS. Phase 2b trial results demonstrated tolebrutinib was well tolerated and identified a dose-dependent reduction in new/enlarging MRI lesions.
Design/Methods:
The phase 2b study was a randomized, double-blind, placebo-controlled, cross-over, dose-ranging trial. HAD was defined as 1 relapse in the year prior to screening and ≥1 gadolinium (Gd)-enhancing lesion on MRI performed within 6 months prior to screening, or ≥9 T2 lesions at baseline or ≥2 relapses in the year prior to screening.
Results:
Of 130 enrolled participants, 61 (47%) met HAD criteria at baseline. Patients with HAD composed 44% of the placebo cohort (29/66) who later crossed over to tolebrutinib treatment. HAD patients were distributed across each tolebrutinib dose arm (12/33 [36%], 19/32 [59%], 16/33 [48%], and 14/32 [44%] in the 5, 15, 30, and 60 mg arms, respectively). After 4 weeks of placebo treatment, the HAD subgroup had mean 0.89 Gd-enhancing lesions and 1.44 new/enlarging T2 lesions. After 12 weeks of tolebrutinib treatment, mean numbers of new Gd-enhancing lesions in the HAD subgroups were 0.82 (5 mg), 0.5 (15 mg), 0.38 (30 mg), and 0.08 (60 mg). Respective numbers of new/enlarging T2 lesions were 1.09 (5 mg), 0.89 (15 mg), 0.75 (30 mg), and 0.15 (60 mg). Tolebrutinib was well tolerated over 12 weeks.
Conclusions:
This subgroup analysis shows that 12-week treatment with tolebrutinib 60 mg effectively reduced new Gd-enhancing and new/enlarging T2 lesions in RMS patients with HAD, consistent with its previously reported effects in the overall study population.