Tolebrutinib Remains Safe, Effective for Relapsing MS With Highly Active Disease

Tolebrutinib has favorable safety and tolerability profile among patients with relapsing MS with highly active disease.

Among patients with multiple sclerosis (MS) categorized as having highly active disease, the Bruton tyrosine kinase inhibitor, tolebrutinib, exhibited an encouraging safety and tolerability profile, as well as a low annualized relapse rate (ARR). These are the results of a study presented at the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held from May 31 to June 3 in Aurora, Colorado.

Researchers aimed to evaluate the safety, efficacy, and magnetic resonance imaging (MRI) profiles of 60 mg tolebrutinib for the treatment of patients with highly active, relapsing MS at week 96 in a phase 2b long-term safety (LTS) extension trial ( Identifier: NCT03996291).

In Part A of the initial LTS, patients received tolebrutinib at doses of 5, 15, 30, or 60 mg/day. Following this double-blind segment, patients entered the Part B, open-label portion where they were all treated with tolebrutinib 60 mg/d.

Analyzed outcomes included gadolinium- (Gd) enhancing T1 lesion counts, number of new or growing T2 lesions, ARR, and overall Expanded Disability Status Scores (EDSS).

Through LTS extension W96, in the HAD cohort, tolebrutinib 60 mg demonstrated favorable safety (similar to the overall population), tolerability, and low ARR.

In total, 59/60 patients continued onto the second portion of the LTS, dropping to 55 patients as of March 7, 2022.

Among patients treated with 60 mg tolebrutinib in both Parts A and B, the number of new Gd-enhancing T1 lesions remained low through week 96 (mean±SD, 0.23±0.44). Results were similar and lesions were reduced among the other dosage groups from weeks 48 to 96, with the exception of those initially treated with 5 mg/d at week 96 (2.00±3.83).

Counts for new or enlarging T2 lesions remained low among patients initially receiving 15, 30, or 60 mg/d of tolebrutinib, with T2 lesion volume remaining unchanged among those who had always received 60 mg/d.

Among patients receiving tolebrutinib 60 mg/d for at least 8 weeks, 92.9% had no relapses at week 96, with an ARR of 0.10. Mean EDSS scores remained steady up to week 96.

No treatment-emergent adverse events related to dosage were found in Part A of the study, with safety profiles remaining the same for patients switching to 60 mg/d in Part B.

The researchers concluded, “Through LTS extension W96 [week 96], in the HAD [highly active disease] cohort, tolebrutinib 60 mg demonstrated favorable safety (similar to the overall population), tolerability, and low ARR.”


Fox RJ, et al. Magnetic resonance imaging, efficacy, and safety of tolebrutinib in participants with highly active disease: 2-year data from the phase 2b long-term safety study. Abstract presented at: CMSC 2023; May 31-June 3, 2023; Aurora, CO. Abstract DMT57.