{"id":1850,"date":"2026-04-20T08:16:56","date_gmt":"2026-04-20T08:16:56","guid":{"rendered":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/04\/20\/aan-2026-the-first-btk-inhibitor-for-ppms-to-make-it\/"},"modified":"2026-04-20T08:16:56","modified_gmt":"2026-04-20T08:16:56","slug":"aan-2026-the-first-btk-inhibitor-for-ppms-to-make-it","status":"publish","type":"post","link":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/04\/20\/aan-2026-the-first-btk-inhibitor-for-ppms-to-make-it\/","title":{"rendered":"AAN 2026 The First BTK inhibitor for PPMS to Make-It?"},"content":{"rendered":"
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So it looks like Fenebrutinib may make it where other BTK inhibiotrs has so far failed. The drug inibits relapsing and primary progressive MS in regard to primary progressive MS it is no worse than ocrelizumab and make be a little better.<\/p>\n

The main difference between fenebrutinib and the past failures are that it is reversible because it does not permanently bind to Brutons Tyrosine kinase. No the fact that the Brutons Trysoine kinase can be permanently bound does not mean that you have to take it one once because the target is been made all the time and you would have to take it more to block the BTK. However, another bit of evolution here and if you permanently block BTK you start producing a version of BTK that lacks the amino acid (cysteine at position 481 of the molecule) that is targeted by the permanent inhibitors and so stops them working. This issue has been seen before with permanent inhibitors used in cancer. I wish we had published our review years ago where we predicted this issue that we never really mentioned. It is interesting that one compnay that was one of the leaders in the BTK ditched their irreversible inhibitor and went to the back of the race to develop their reversible plan B….did they find something all those years ago…we may find that tortoise getting to market where the other March Hares have all be shot before they got to the end of the race.<\/p>\n

The liver problem which has so far been a problem for the others and seemed to be blocking tolebrutinib in development for progressive MS is less of an issue. I suspect it will need to be monitored. The liver is the major filtering organ in the body and it is jam packed with macrophages called kupffer cells that express BTK and will no doubt be targeted by this class of drug. Pharma are spinning the story that the side effects are caused by the fact that some of the inhibitors target alot of other kinases.<\/p>\n

Efficacy and Safety of Fenebrutinib vs Ocrelizumab in Primary Progressive Multiple Sclerosis: Primary Results of the Phase III FENtrepid Study<\/p>\n

Amit Bar-Or1<\/sup>, Jiwon Oh2<\/sup>, Gavin Giovannoni3<\/sup>, Maria Pia Sormani4<\/sup>, Martin S. Weber5<\/sup>, Sharon Stoll6<\/sup>, Jacqueline A. Nicholas7<\/sup>, H.-Christian von B\u00fcdingen8<\/sup>, Jon Lopez9<\/sup>, Louise Roberts9<\/sup>, Miriam Triyatni8<\/sup>, Qi Qi9<\/sup>, John N. Ratchford9<\/sup>, Julie Napieralski9<\/sup>, Alexandra Goodyear9<\/sup>, Stephen L. Hauser10<\/sup>, Ludwig Kappos11<\/sup>
1<\/sup>Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, 2<\/sup>St. Michael\u2019s Hospital, University of Toronto, Toronto, ON, Canada, 3<\/sup>Queen Mary University of London, London, UK, 4<\/sup>University of Genoa, Genoa, Italy, 5<\/sup>Institute of Neuropathology and Department of Neurology, University Medical Center and Fraunhofer Institute for Translational Medicine and Pharmacology, G\u00f6ttingen, Germany, 6<\/sup>Advocare Stoll Medical Group, Philadelphia, PA, USA, 7<\/sup>OhioHealth Multiple Sclerosis Centre, Riverside Methodist Hospital, Columbus, OH, USA, 8<\/sup>F. Hoffmann-La Roche Ltd, Basel, Switzerland, 9<\/sup>Genentech, Inc., South San Francisco, CA, USA, 10<\/sup>University of California San Francisco, San Francisco, CA, USA, 11<\/sup>University Hospital and University Basel, Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Basel, Switzerland<\/p>\n

Objective:To evaluate the efficacy and safety of fenebrutinib compared with ocrelizumab in adult patients with primary progressive multiple sclerosis (pwPPMS).<\/p>\n

Background:Bruton’s tyrosine kinase inhibitors (BTKi) have potential to impact both relapsing and progressive MS disease biologies. Fenbrutinib is an oral, highly selective, noncovalent, reversible BTKi that is CNS-penetrant, as shown in the Phase II FENopta study (NCT05119569) in relapsing MS in which fenebrutinib treatment rapidly reduced acute inflammatory disease activity. Currently the effect of fenebrutinib on progressive MS subtypes has not been demonstrated. Ocrelizumab remains the only approved treatment for PPMS, and an unmet need exists for treatments that can better control disability progression. FENtrepid (NCT04544449) is the first clinical trial of a new therapy in PPMS using ocrelizumab as an active comparator.<\/p>\n

Design\/Methods: FENtrepid is a Phase III, multicenter, randomized, double-blind, double-dummy, parallel-group study evaluating the efficacy and safety of fenebrutinib compared with ocrelizumab in pwPPMS (18-65 years old; PPMS diagnosis [2017 revised McDonald criteria]; Expanded Disability Status Scale [EDSS] score 3.0-6.5). Patients were randomized 1:1 to either oral fenebrutinib 200 mg twice daily or intravenous ocrelizumab 600 mg every 24 weeks. The primary endpoint was time to onset of composite confirmed disability progression, defined as a 12-week confirmed increase in one or more of the EDSS, Timed 25-Foot Walk Test or 9-Hole Peg Test.<\/p>\n

Results: FENtrepid enrolled 985 patients with PPMS; 84% were not exposed to recent prior disease modifying therapies. Mean (SD) age at baseline was 48.9 (10.3) years. Median baseline EDSS score was 5.0; mean (SD) duration since MS symptom onset and diagnosis was 9.0 (6.7) and 4.7 (5.4) years, respectively. Primary efficacy and safety results will be presented.<\/p>\n

Conclusions:FENtrepid will provide the first evidence on the effect of fenebrutinib treatment on disability progression in PPMS, relative to an active comparator of ocrelizumab.<\/p>\n

10.1212\/WNL.0000000000216067;<\/p>\n

You can’t wait for the result well companies tell their shareholders the results first before the science medium gets the information this info is 2 months old and was presented at ACTIMS2026<\/p>\n