Sanofi gets USFDA Breakthrough Therapy designation for multiple sclerosis therapy Tolebrutinib

Liver enzyme elevations (>3xULN) were observed in 4.1% of participants receiving tolebrutinib compared with 1.6% in the placebo group. A small (0.5%) proportion of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, all occurring within the first 90 days of treatment. All but one case of liver enzyme elevations resolved without further medical intervention. The implementation of more frequent monitoring has helped mitigate serious liver sequelae.

Multiple sclerosis is a chronic, immune-mediated, neurodegenerative disease that may result in accumulation of irreversible disabilities over time. The physical and cognitive disability impairments translate into gradual deterioration of health status, impacting patients’ care and quality of life. Disability accumulation remains the significant unmet medical need in MS. To date, the primary target of current medicines has been peripheral B and T cells, while innate immunity, which is believed to drive disability accumulation, remains largely unaddressed by current medicines. Currently approved, or late-stage medicines being tested for MS mainly target the adaptive immune system and/or do not act directly within the central nervous system to drive clinical benefit.

nrSPMS refers to people with MS who have stopped experiencing relapses but continue to accumulate disability, experienced as symptoms such as fatigue, cognitive impairment, balance and gait impairment, loss of bowel and/or bladder function, sexual disfunction, amongst others.

Regulatory submissions of tolebrutinib are currently being finalized for the US and prepared for the EU. As with other medicines, Sanofi plans to confirm once a regulatory submission for tolebrutinib has been accepted. The PERSEUS phase 3 study in primary progressive MS is currently ongoing with study results anticipated in H2 2025.

Tolebrutinib is an investigational, oral, brain-penetrant, and bioactive Bruton’s tyrosine kinase (BTK) inhibitor that achieves cerebrospinal fluid concentrations predicted to modulate B lymphocytes and disease-associated microglia. Tolebrutinib is being evaluated in phase 3 clinical studies for the treatment of various forms of multiple sclerosis and its safety and efficacy have not been evaluated by any regulatory authority worldwide.