Sanofi's tolebrutinib has met its primary endpoint in the HERCULES study.
The Phase III trial looked into how the oral BTK inhibitor could delay the onset of confirmed disability progression (CDP) in patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS) — finding that tolebrutinib exhibited clinically meaningful improvements in CDP compared to placebo.
Although results from the GEMINI 1 and 2 Phase III studies found that tolebrutinib didn't meet the primary endpoint (reducing annualised relapse rate compared to teriflunomide), analysis of data for key secondary endpoints found the drug could significantly delay time to onset.
Sanofi's Head of Research & Development, Houman Ashrafian, commented: “Tolebrutinib represents an unprecedented breakthrough as a potential first-in-disease treatment option with clinically meaningful benefit in disability accumulation. Addressing disability accumulation, thought to be driven by smoldering neuroinflammation, remains the greatest unmet medical need in people with non-relapsing secondary progressive MS today.”
Sanofi is also currently running the PERSEUS Phase III study, which is evaluating the time to onset of CDP in patients with primary progressive multiple sclerosis.
The results of this trial should be available by 2025, according to the pharmaceutical company.
Significant unmet needs remain in the MS patient population
Multiple sclerosis is a chronic neurodegenerative disease that results in patients experiencing an accumulation of irreversible disabilities over time.
These physical and cognitive impairments then translate into the graduation deterioration of health and quality of life, which can significantly impact a patient's life expectancy.
Disability accumulation remains the significant unmet medical need in MS. To date, the primary target of current therapies has been peripheral B and T cells, while innate immunity, which is believed to drive disability accumulation, remains largely unaddressed by current therapies.
Tolebrutinib's mechanism of action modulates both B lymphocytes and activated microglia in the CNS, which is understood to address the underlying mechanisms of disability accumulation in MS linked to smoldering neuroinflammation in the brain and spinal cord.
