MRI Outcomes from the Long-term Extension Study of Tolebrutinib in Patients with Relapsing Multiple Sclerosis: 18-Month Results
Daniel Reich1, Anthony Traboulsee2, Sana Syed3, Deborah Dukovic3, Timothy Turner3, Douglas Arnold4
1National Institutes of Health, Neuroimmunology Branch, NINDS, 2University of British Columbia, 3Sanofi, 4Montreal Neurological Institute, McGill Univ
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.