Sanofi Tolebrutinib under USFDA priority review for multiple sclerosis
Tolebrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.
Paris: Sanofi has announced that the US Food and Drug Administration (FDA) is evaluating under priority review the regulatory submission of tolebrutinib to treat non-relapsing secondary progressive multiple sclerosis (nrSPMS) and to slow disability accumulation independent of relapse activity in adult patients.
The target action date for the FDA decision is September 28, 2025. A regulatory submission is also under review in the EU.
The regulatory submissions in the US and the EU are supported by the results from the phase 3 studies HERCULES in nrSPMS and GEMINI 1 and 2 in relapsing MS (RMS). The findings from these studies, as well as additional clinical and preclinical studies, support the differentiated mechanism of tolebrutinib to target disability progression independent of relapse activity, and the scientific hypothesis that smoldering neuroinflammation represents a key inflammatory process in MS and is a critical driver of disability accumulation.
Erik Wallström, MD, PhD, Global Head of Neurology Development said, “The totality of data across our clinical program validates our scientific understanding of smoldering neuroinflammation as a distinct inflammatory process in MS. People living with non-relapsing secondary progressive multiple sclerosis or who experience disability independent of relapse activity suffer from disability that worsens over time due to persistent inflammation in the brain, known as smoldering neuroinflammation, which is the primary driver of disability. The demonstrated ability of tolebrutinib to delay disability by targeting underlying drivers of the disease represents a potential paradigm shift in treating these patients.”
Tolebrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority. The PERSEUS phase 3 study of tolebrutinib in patients with primary progressive MS is currently ongoing with study results anticipated in H2 2025.
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 currently approved medicines has been peripheral B and T cells, while innate immunity within the CNS, which is believed to drive disability accumulation, remains largely unaddressed. 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.
Living with 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.
Tolebrutinib is an investigational, oral, brain-penetrant, and bioactive Bruton’s tyrosine kinase (BTK) inhibitor specifically designed to target smoldering neuroinflammation, a key driver of disability progression in MS. Unlike currently approved MS therapies that primarily address peripheral inflammation, tolebrutinib uniquely crosses the blood-brain barrier to achieve therapeutic cerebrospinal fluid concentrations, allowing it to modulate B-lymphocytes and disease-associated microglia within the CNS. This mechanism is believed to address the underlying pathology of progressive MS by targeting the inflammatory processes that contribute to neurodegeneration and disability accumulation.
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.
