Tolebrutinib Reduces New Lesions in People with Highly Active Multiple Sclerosis

A subgroup analysis of participants with highly active multiple sclerosis (MS) in a clinical trial (NCT03889639) of tolebrutinib (Sanofi; Bridgewater, NJ) had reduced disease activity with tolebrutinib vs placebo. After 12 weeks of treatment with tolebrutinib 60 mg the number of new gadolinium-enhancing (Gd⁺) and new or enlarging lesions on T2 MRI were reduced (Table). These findings are consistent with those seen in the overall study population.

Tim Turner, the gobal project head for Neurology at Sanofi said, “BTK signaling plays a key role in the activation of various innate immune cells believed to drive neuroinflammation and chronic lesion formation. A CNS-penetrant BTK inhibitor may modulate both adaptive (B-cell activation) and innate (CNS microglial cells) immune cells thought to be linked to neuroinflammation and neurodegeneration in the brain and spinal cord, which are markers of disease progression in people living with multiple sclerosis (MS). This dual mechanism could ultimately make CNS-penetrant BTK inhibitors an important treatment option across the full spectrum, including relapsing MS as well as progressive disease, where treatment options are extremely limited.”

Tolebrutinib is a Bruton tyrosine kinase inhibitor and was well tolerated over 12 weeks.

Almost half of participants who were treated with tolebrutinib (61/130; 47%) had highly active MS at baseline and these individuals comprised 36%, 59%, 48%, and 44% of the groups that received 5, 15, 30, and 60 mg tolebrutinib, respectively. In the placebo group (n=66), 44% of participants had highly active MS. 

Highly active MS was defined as at least 2 relapses in the year before screening, or 1 relapse in the year before screening and at least 1 Gd⁺ lesion on MRI in the 6 months before screening, or at least 9 T2 lesions at baseline. This dose-ranging trial was randomized, double-blind and placebo controlled.

These data were presented at the virtual 2021 American Academy of Neurology (AAN) Virtual Annual Meeting April 17-22, 2021.