{"id":1857,"date":"2026-04-21T08:24:45","date_gmt":"2026-04-21T08:24:45","guid":{"rendered":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/04\/21\/aan2026-can-tolebrutinib-be-revived\/"},"modified":"2026-04-21T08:24:45","modified_gmt":"2026-04-21T08:24:45","slug":"aan2026-can-tolebrutinib-be-revived","status":"publish","type":"post","link":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/04\/21\/aan2026-can-tolebrutinib-be-revived\/","title":{"rendered":"AAN2026 Can Tolebrutinib be revived?"},"content":{"rendered":"
Tweet<\/a><\/div>\n

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<\/p>\n

It failed to beat teriflunomide in relapsing MS and here they have pulled out the primary progressive MS data. <\/p>\n

Can Efficacy and Safety of Tolebrutinib Versus Placebo in Primary Progressive Multiple Sclerosis: Results from the Phase Three PERSEUS Trial<\/p>\n

Robert Fox1<\/sup>, Amit Bar-Or2<\/sup>, Patrick Vermersch3<\/sup>, Celia Oreja Guevara4<\/sup>, Anthony Traboulsee5<\/sup>, Gavin Giovannoni6<\/sup>, Sana Syed7<\/sup>, Furong Sun7<\/sup>, Naji Salloum7<\/sup>, Timothy Turner7<\/sup>, Erik Wallstroem7<\/sup>, Daniel Reich8<\/sup>
1<\/sup>Cleveland Clinic, 2<\/sup>University of Pennsylvania, 3<\/sup>University of Lille, 4<\/sup>Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos, 5<\/sup>University of British Columbia, 6<\/sup>Queen Mary University London, 7<\/sup>Sanofi, 8<\/sup>Translational Neuroradiology Section, National Institutes of Health<\/p>\n

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).<\/p>\n

Background:Treatment options remain limited for people with PPMS, with only one approved therapy. Tolebrutinib is an oral, brain-penetrant, and bioactive Bruton\u2019s 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.<\/p>\n

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.<\/p>\n

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 na\u00efve. 89% of participants had no gadolinium-enhancing lesions at baseline. In the subset of participants with susceptibility-sensitive imaging, 63% had \u22651 paramagnetic rim lesions at baseline. Efficacy and safety results of PERSEUS will be presented at AAN, as well as subgroup analyses.<\/p>\n

Conclusions: The presented PERSEUS trial results will provide an assessment of tolebrutinib efficacy and safety in people with PPMS.<\/p>\n

10.1212\/WNL.0000000000216118<\/p>\n<\/p>\n

Source: multiple-sclerosis-research.org<\/a><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Tweet 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…<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[11,15,9,8,13,14,12,10],"class_list":["post-1857","post","type-post","status-publish","format-standard","hentry","category-multiple-sclerosis-research","tag-brain-repair","tag-marburg-type-ms","tag-ms","tag-multiple-sclerosis","tag-myelin","tag-neuroregeneration","tag-oligodendrocyte","tag-remyelination"],"_links":{"self":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/1857","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/comments?post=1857"}],"version-history":[{"count":0,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/1857\/revisions"}],"wp:attachment":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/media?parent=1857"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/categories?post=1857"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/tags?post=1857"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}