By targeting both arms of the immune system, not just B cells, brain-penetrant inhibitors of Bruton’s tyrosine kinase could improve on anti-CD20 therapy for patients with multiple sclerosis.
Sanofi is going all-in on the strategy of targeting Bruton’s tyrosine kinase (BTK) to control autoimmunity. In September, the French drug giant completed a $3.7 billion takeover of Principia Biopharma, maker of three covalent BTK inhibitors in development for the treatment of various autoimmune conditions.
One particular BTK blocker, the brain-penetrant agent tolebrutinib, is the cornerstone for the acquisition. The two companies forged a previous licensing deal in 2017 over this agent, which entered phase 3 testing last year for both relapsing and progressive forms of multiple sclerosis (MS). Sanofi is now in a three-way contest with Merck KGaA and Genentech, both of which have their own anti-BTK drugs in late-stage trials for MS as well (Table 1).
The idea of targeting BTK in autoimmunity flows from the success of CD20-directed antibodies, such as rituximab (now generic) and Genentech’s Ocrevus (ocrelizumab), as therapies for rheumatoid arthritis, MS and other disorders marked by autoreactive B cells. Yet, whereas anti-CD20 drugs completely wipe out all B cells, leaving people prone to opportunistic infections, BTK inhibitors — which block a critical enzyme involved in B cell maturation — may more selectively remove unwanted B cells while leaving healthy ones alone.
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