Recently we were talking about the hare and the tortoise and the first hares related to bruton tyrosine kinase irreversible inhibitors failed to beat teriflunomide in trials in relapsing MS. We then heard an reversible inhibitor was active and at that point I asked if one company was correct to bin their first effort called orlabrutinib to create a reversible inhibitor
but here they write “They say “BIIB091 is a peripherally acting small molecule kinase inhibitor that is being developed as a reversible oral treatment option for MS”. So here I ask “how this will fare?”. If it is peripherally active it implies it doesn’t get into the CNS and so you ask what is the likely benefit for progressive MS? So the big question is how it will compare to B cell depleting antibodies? They are doing a study probably now finished based on information in the trial design
“A Study to Learn About the Safety of BIIB091 and Its Effect on Brain Inflammation When Taken Alone or With Diroximel Fumarate (DRF) in Adults With Relapsing Forms of Multiple Sclerosis (MS) (FUSION)”
Tsai HH, Gu Y, Riester K, Chu SS, Bame E, Arefayene M, Kam JL, Coppell A, Hanna J, Hopkins BT, Scaramozza M. First-in-Human Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of BIIB091, an Oral BTK Inhibitor, in Healthy Adult Participants. Drug Des Devel Ther. 2026;20:571780.
Multiple sclerosis (MS) affects 2.8 million people globally. Despite available disease-modifying therapies (DMTs), more effective treatments are needed to prevent/slow disability progression. BIIB091 is a selective, non-covalent oral Bruton’s tyrosine kinase (BTK) inhibitor. This Phase 1, first-in-human study evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BIIB091.
Participants received single ascending doses (SAD; 50–1200 mg) or multiple ascending doses (MAD; 50–300 mg twice daily [BID] for 14 days) of BIIB091 or placebo.
Sixty-four participants were randomized (SAD n=40; MAD n=24). BIIB091 showed rapid absorption, dose-proportional PK, and no significant accumulation. BIIB091 was well tolerated at single doses up to 1200 mg and repeated doses up to 300 mg BID, showing dose-linear PK and sustained effective B cell activation suppression. BIIB091 PK appeared to be sensitive to food effect.
Source: multiple-sclerosis-research.org