Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis

In this phase 3, double-blind, placebo-controlled trial (HERCULES), researchers assessed the effect of tolebrutinib a brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor on disability progression in 1131 patients with nonrelapsing secondary progressive multiple sclerosis (SPMS), a form of MS with no approved treatments for progression independent of relapse. Participants were randomized 2:1 to receive tolebrutinib (60 mg daily) or placebo. After a median follow-up of 133 weeks, 22.6% of patients in the tolebrutinib group and 30.7% in the placebo group experienced confirmed disability progression sustained for at least 6 months (HR 0.69; 95% CI, 0.55–0.88; P=0.003). Tolebrutinib also reduced new or enlarging T2 lesions on MRI and increased the rate of disability improvement. Liver enzyme elevations occurred more frequently in the tolebrutinib group, including one case of liver failure. The findings suggest that tolebrutinib may slow disability accrual in nonrelapsing SPMS, though monitoring for hepatotoxicity is warranted.

In this phase 3, double-blind, placebo-controlled trial (HERCULES), researchers assessed the effect of tolebrutinib a brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor on disability progression in 1131 patients with nonrelapsing secondary progressive multiple sclerosis (SPMS), a form of MS with no approved treatments for progression independent of relapse. Participants were randomized 2:1 to receive tolebrutinib (60 mg daily) or placebo. After a median follow-up of 133 weeks, 22.6% of patients in the tolebrutinib group and 30.7% in the placebo group experienced confirmed disability progression sustained for at least 6 months (HR 0.69; 95% CI, 0.55–0.88; P=0.003). Tolebrutinib also reduced new or enlarging T2 lesions on MRI and increased the rate of disability improvement. Liver enzyme elevations occurred more frequently in the tolebrutinib group, including one case of liver failure. The findings suggest that tolebrutinib may slow disability accrual in nonrelapsing SPMS, though monitoring for hepatotoxicity is warranted.