Sanofi (SAN) Status Update summary

Key clinical trial results and efficacy

• Tolebrutinib delayed 6-month confirmed disability progression by 31% in non-relapsing secondary progressive MS (nrSPMS) compared to placebo, with nearly double the proportion achieving confirmed disability improvement.

• In relapsing MS (RMS), tolebrutinib did not significantly reduce annualized relapse rates versus teriflunomide/Aubagio, but showed a 29% risk reduction in 6-month confirmed disability worsening.

• Both trials reported low relapse rates, well-balanced baseline characteristics, and high study completion rates.

• Tolebrutinib's impact on disability progression in RMS aligns with the benefit seen in nrSPMS, suggesting efficacy against progression independent of relapses.

• Significant reduction in annualized rate of new/enlarging T2 lesions was observed in nrSPMS.

Safety and liver monitoring

• Liver enzyme elevations (>3x ULN) occurred in 5.6% of RMS and 4.1% of nrSPMS patients on tolebrutinib, with most resolving without sequelae; one fatal case occurred before enhanced monitoring.

• Enhanced liver monitoring protocols require weekly assessments during the first 12 weeks, considered manageable by clinicians.

• Adverse event profiles were generally balanced between arms, with common events including COVID-19 infection, nasopharyngitis, and slightly higher respiratory infections in the tolebrutinib group.

• Deaths were balanced across treatment and control arms and assessed as unrelated to treatment.

• Serious liver events were rare and mostly resolved without intervention.

Clinical significance, unmet need, and patient impact

• Tolebrutinib is the first therapy to demonstrate a delay in confirmed disability progression in non-relapsing SPMS, addressing a major unmet need.

• Physicians expect patients to accept the liver monitoring burden and risk, given the lack of alternatives and meaningful reduction in disability progression.

• SPMS is underdiagnosed and undertreated, with tolebrutinib potentially setting a new standard of care.

• Disability accumulation in MS, especially progression independent of relapses, remains a significant unmet need.

• Current MS therapies mainly target peripheral immune cells and do not address CNS-driven progression.