Biogen’s search for improved BTK inhibition lands orelabrutinib


In licensing Innocare’s BTK inhibitor orelabrutinib for multiple sclerosis Biogen might look like it is following the lead of Sanofi, which last year bought Principia for the same purpose. But Biogen has actually been in the BTK game for some years. Not only did it license the now abandoned non-covalent vecabrutinib for oncology use to Sunesis in 2014, it has its own MS contender, BIIB091, in phase 1. The attraction of Innocare’s orelabrutinib, a covalent molecule Biogen picked up yesterday for $125m up front, is its brain penetrance, given that crossing the blood-brain barrier is important for an MS therapy. Orelabrutinib is already approved in China for haematological cancers, and a phase 2 MS trial started in March. Biogen likely went looking specifically for a brain-penetrant BTK inhibitor, and says this property could give orelabrutinib an advantage over the competition, which in MS includes Sanofi’s tolebrutinib and Merck KGaA’s evobrutinib. Still, Sanofi and Merck alike have boasted of their candidates’ superior CNS penetration. Perhaps the bigger issue is that conclusive proof of BTK inhibition’s applicability in MS has yet to emerge, something to which the small number of competitors attests.

BTK inhibitors with potential specifically in multiple sclerosis (MS)
Project Company Status
Tolebrutinib (SAR442168) Sanofi (ex Principia) Large ph3 programme in relapsing-remitting (vs Aubagio), primary progressive (vs placebo) & non-relapsing secondary progressive (vs placebo) MS
Evobrutinib Merck KGaA Ph3 in relapsing MS vs Aubagio (Avonex comparator trials terminated)
Fenebrutinib* (RG7845) Roche Ph3 in relapsing (vs Aubagio) and primary progressive (vs Ocrevus) MS
Orelabrutinib (ICP-022) Biogen/Innocare Ph2 relapsing-remitting MS trial vs placebo started in Mar 2021
BIIB091* Biogen Ph1 volunteer study
BIIB068 Biogen Discontinued after ph1
Note: *non-covalent; the remainder are covalent molecules. Source: Evaluate Pharma &

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