Long-Term Study Demonstrates Reduction of Lesion Counts in Tolebrutinib Treated Participants With Relapsing Multiple Sclerosis
The results of a long-term safety (LTS) extension study (NCT03996291) presented at the 2023 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) reported reduced lesion counts in those receiving tolebrutinib (Sanofi, Paris, France) for treatment of relapsing multiple sclerosis (RMS). Tolebrutinib is a brain-penetrant Bruton tyrosine kinase inhibitor under investigation as a potential treatment for RMS.
The LTS extension study included data from 114 participants (mean age ± SD = 37.7 ± 9.6 y; 69% women) who completed a double-blind phase (DBP) 2b clinical trial (NCT03889639) that demonstrated a dose-dependent reduction in gadolinium (Gd)-enhancing T1 and new/enlarging T2 lesions. After a 0-21 week variable treatment gap, participants began the LTS study and continued receiving their DBP 2b clinical trial tolebrutinib dose (5, 15, 30, or 60 mg/d) in a double-blind manner for 48 weeks, at which point all participants received the phase 3 tolebrutinib dose of 60 mg until the week 96 cutoff.
At week 96, MRI was used to assess Gd-enhancing T1 and T2 lesions. The number of new Gd-enhancing lesions remained low in the 60/60 mg arm through week 96 and were reduced in other arms at week 48 through week 96 (96 wk mean ± SD: 0.85 ± 2.5, 0.41 ± 0.91, 0.90 ± 2.16, 0.31 ± 0.66 in the 5/60 mg, 15/60 mg, 30/60 mg, 60/60 mg arms, respectively). T2 lesion volume change remained low for the 60/60 mg arm (96 wk vs baseline [mean ± SD], 0.38 ± 2.11 cm3). Median (IQR) week 96 slowly evolving lesions (SELs) volume was 247.5 (84–420), 258 (66–906), 570 (133.5–1011), and 244.5 (87–939) mm3 for the 5/60 mg, 15/60 mg, 30/60 mg, and 60/60 mg arms, respectively. Paramagnetic rim lesion (PRL) count remained unchanged in 18 participants; 2 participants had 1 PRL at baseline but none at week 96, and 3 participants had 1 to 3 additional PRLs at week 96 vs baseline (none in the 60/60 mg arm), all of which corresponded to new T2 lesions.
Researchers for this study received support from and represent a variety of organizations and companies, including Sanofi, Novartis, Abata, National Institutes of Health, National Institute of Neurological Disorders and Stroke, Roche, Biogen, Celgene, Frequency Therapeutics, Genentech, Merck, Race to Erase MS, and Xfacto Communications.