Based on the submission of additional analyses during the review, the FDA has determined that the additional information constituted a major amendment to the NDA and extended the target action date accordingly. The revised target action date for the FDA decision is December 28, 2025. Tolebrutinib was the first brain-penetrant BTK inhibitor in nrSPMS to be designated as a breakthrough therapy by the FDA. Disability accumulation remains a significant unmet medical need in MS. Currently, 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.