French pharmaceutical giant Sanofi (SNYNF, SNY) has announced that its oral brain-penetrant Bruton's tyrosine kinase (BTK) inhibitor, Tolebrutinib, successfully met the primary endpoint in the HERCULES phase 3 study by delaying the onset of confirmed disability progression (CDP) in patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS).
However, results from the GEMINI 1 and 2 phase 3 studies, which evaluated Tolebrutinib in patients with relapsing forms of multiple sclerosis (RMS), did not meet the primary endpoint of reducing the annualized relapse rate (ARR) compared to teriflunomide. Despite this, an analysis of the key secondary endpoint in pooled 6-month CDP data indicated a significant delay in onset, corroborating the findings from the HERCULES study.
Multiple sclerosis (MS) is a chronic, immune-mediated, neurodegenerative disease that leads to the accumulation of irreversible disabilities over time. Sanofi noted that the results from these phase 3 studies will inform future discussions with global regulatory authorities.
The HERCULES phase 3 study is notable for being the first and only trial to demonstrate a reduction in disability accumulation. Preliminary analysis of liver safety in the latest trial was in line with previous Tolebrutinib studies.
Houman Ashrafian, Head of Research & Development at Sanofi, stated, "Tolebrutinib represents an unprecedented breakthrough as a potential first-in-disease treatment option offering clinically meaningful benefits in disability accumulation. Addressing disability accumulation, believed to be driven by smoldering neuroinflammation, remains the greatest unmet medical need for individuals with non-relapsing secondary progressive MS today."
The company plans to present the study results for HERCULES, along with GEMINI 1 and 2, at the upcoming European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) medical meeting on September 20.
It should be noted that Tolebrutinib is still under clinical investigation and has not been evaluated for safety or efficacy by any regulatory authority. Additionally, the PERSEUS phase 3 study, which is assessing time to onset of CDP in primary progressive MS, is ongoing with results expected in 2025.
