Tolebrutinib treatment shows 'dose-dependent reduction' in certain RMS-related lesions
Treatment with tolebrutinib 60 mg for 12 weeks reduced new gadolinium-enhancing and new or enlarging T2 lesions among patients with relapsing MS who had highly active disease.
Researchers presented the results of a subgroup analysis of a phase 2b study that included 130 participants at the American Academy of Neurology annual meeting, which was held virtually.
“Many people with MS will experience increasing disability over the course of their lifetime. In patients with relapsing remitting MS, highly active disease (HAD) is associated with a more aggressive disease course, which can have a significant impact on all areas of an individual’s health and daily life,” Sana Syed, MD, MPH, clinical lead of MS, neurology and gene therapy at Sanofi Genzyme, told Healio Neurology. “Our intention with this study was to examine the potential impact of our oral, central nervous system-penetrant Bruton’s tyrosine kinase inhibitor, tolebrutinib, on several neuroinflammatory processes known for driving progression and higher disease activity levels, in MS. Specifically, this analysis examined the MRI efficacy and safety of tolebrutinib in patients with highly active relapsing MS.”
The phase 2b study was a randomized, double-blind, placebo-controlled, cross-over, dose-ranging trial. Syed and colleagues defined highly active disease as the occurrence of one relapse in the year before screening and one or more gadolinium (Gd)-enhancing T1 lesions on MRI conducted 6 months or less before screening, or nine or more T2 lesions at baseline or two or more relapses in the year before screening.
Results showed 61 (47%) of 130 enrolled participants met criteria for highly active disease at baseline. A total of 44% of participants (n = 29) in the placebo cohort (n = 66) had highly active disease and later crossed over to tolebrutinib treatment. Patients with highly active disease composed 36%, 59%, 48% and 44% of the 5, 15, 30 and 60 mg tolebrutinib treatment dose arms, respectively.
Syed and colleagues reported mean numbers of Gd-enhancing lesions and new or enlarging T2 lesions of 0.89 and 1.44, respectively, among the highly active disease subgroup after 4 weeks of placebo treatment. They reported mean numbers of new Gd-enhancing lesions among the highly active disease subgroups after 12 weeks of tolebrutinib treatment of 0.82 for the 5 mg arm, 0.5 for the 15 mg arm, 0.38 for the 30 mg arm and 0.08 for the 60 mg arm. The 5 mg, 15 mg, 30 mg and 60 mg arms exhibited respective numbers of new or enlarging T2 lesions of 1.09, 0.89, 0.75 and 0.15. Over 12 weeks, tolebrutinib was well tolerated, according to the researchers.
“Our findings suggested a positive efficacy impact for the tolebrutinib 60 mg dose in reducing lesions for patients with relapsing MS with HAD in the study. Tolebrutinib was also well tolerated over 12 weeks in patients with HAD, consistent with previously reported effects in the overall study population,” Syed said. “Therefore, it would be of interest to continue to evaluate the efficacy in this population as additional data becomes available.”