Tolebrutinib which is a irreversible BTK inhibitor was shown in a trial to inhibit non-relapsing progressive MS, but development has been held up in US because of liver damage signals. Results from the HERCULES phase 3 study showed delay in disability progression in people living with non-relapsing secondary progressive multiple sclerosis
It failed to beat teriflunomide in relapsing MS and here they have pulled out the primary progressive MS data.
Can Efficacy and Safety of Tolebrutinib Versus Placebo in Primary Progressive Multiple Sclerosis: Results from the Phase Three PERSEUS Trial
Robert Fox1, Amit Bar-Or2, Patrick Vermersch3, Celia Oreja Guevara4, Anthony Traboulsee5, Gavin Giovannoni6, Sana Syed7, Furong Sun7, Naji Salloum7, Timothy Turner7, Erik Wallstroem7, Daniel Reich8
1Cleveland Clinic, 2University of Pennsylvania, 3University of Lille, 4Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, 5University of British Columbia, 6Queen Mary University London, 7Sanofi, 8Translational Neuroradiology Section, National Institutes of Health
Objective:To present phase 3 data of the PERSEUS trial evaluating the efficacy and safety of tolebrutinib versus placebo in primary progressive multiple sclerosis (PPMS).
Background:Treatment options remain limited for people with PPMS, with only one approved therapy. Tolebrutinib is an oral, brain-penetrant, and bioactive Bruton’s tyrosine kinase inhibitor that modulates persistent immune activation within the CNS, including disease-associated microglia and B cells. In phase 3 pivotal trials, tolebrutinib treatment reduced the risk of disability accumulation versus placebo in non-relapsing secondary progressive MS and versus teriflunomide in relapsing MS.
Design/Methods:PERSEUS (NCT04458051) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven trial. Enrollment criteria included age 18-55 years, diagnosis of PPMS per the 2017 McDonald criteria, Expanded Disability Status Scale (EDSS) score of 2.0-6.5 at screening, positive CSF findings, and either no access, intolerance, or perceived lack of efficacy to ocrelizumab. Participants were randomized 2:1 to receive tolebrutinib 60 mg or placebo, once daily with food. The primary endpoint is time-to-onset of 6-month composite confirmed disability progression (cCDP) as measured by EDSS, Timed 25-Foot Walk, or 9-Hole Peg Test. Secondary endpoints include additional measures of disability, MRI outcomes, and safety.
Results:767 participants were enrolled with a mean age of 45.3 years and mean time since PPMS diagnosis of 4.2 years. Approximately 54% of participants were male, and 83% were white. At baseline, mean EDSS was 4.9 (median, 5.0) and 59% were treatment naïve. 89% of participants had no gadolinium-enhancing lesions at baseline. In the subset of participants with susceptibility-sensitive imaging, 63% had ≥1 paramagnetic rim lesions at baseline. Efficacy and safety results of PERSEUS will be presented at AAN, as well as subgroup analyses.
Conclusions: The presented PERSEUS trial results will provide an assessment of tolebrutinib efficacy and safety in people with PPMS.
10.1212/WNL.0000000000216118
Source: multiple-sclerosis-research.org