Tolebrutinib Receives Breakthrough Therapy Designation for Non-Relapsing Secondary Progressive Multiple Sclerosis
The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to tolebrutinib for the treatment of adults with non-relapsing secondary progressive multiple sclerosis (nrSPMS).
This decision follows promising data from the HERCULES phase 3 study, which demonstrated that tolebrutinib delayed the onset of 6-month confirmed disability progression (CDP) by 31% compared to a placebo (HR 0.69; 95% CI 0.55-0.88; p=0.0026).
Further analysis of secondary endpoints showed that 10% of participants on tolebrutinib experienced confirmed disability improvement, nearly double the 5% seen in the placebo group (HR 1.88; 95% CI 1.10 to 3.21; nominal p=0.021).
FDA Breakthrough Therapy designation is designed to expedite the development and review of treatments for serious or life-threatening conditions. To qualify, a drug must demonstrate preliminary evidence of significantly improving clinically relevant outcomes compared to existing treatments.
In clinical trials, liver enzyme elevations greater than three times the upper limit of normal (ULN) were observed in 4.1% of participants taking tolebrutinib, compared to 1.6% in the placebo group.
A small percentage (0.5%) of participants in the tolebrutinib group experienced peak ALT increases greater than 20xULN, all within the first 90 days of treatment. Most cases of liver enzyme elevation resolved without the need for medical intervention, and increased monitoring is being used to manage potential liver issues.
Tolebrutinib is an investigational oral drug targeting Bruton’s tyrosine kinase (BTK), aimed at modulating B lymphocytes and disease-associated microglia in the central nervous system. It is currently being evaluated in phase 3 clinical trials for multiple sclerosis in various forms. Its safety and efficacy have not yet been assessed by any regulatory authority.
