The holiday season delivered unwelcome news for both Sanofi and Corcept Therapeutics, as each company received FDA rejections tied to their respective drug filings.
Sanofi disclosed the day before Christmas that the FDA had declined to approve its application for tolebrutinib in non-relapsing secondary progressive multiple sclerosis (nrSPMS). The setback was particularly disappointing for the French drugmaker, who had been informed just weeks earlier that the the decision to approve or not would not be made in time for the deadline, which was December 28.
In secondary progressive multiple sclerosis, individuals are usually first diagnosed with relapsing MS but later stop experiencing relapses and instead face gradual worsening of disability. While treatments for MS have advanced in recent years, the company says significant unmet need persists in this stage of the disease because therapeutic options remain limited.
Sanofi received FDA priority review for its nrSPMS application in March and initially projected an approval decision by September 28. As that deadline approached, however, the company disclosed a three-month extension after submitting additional analyses that the FDA deemed substantial enough to alter the application.
As the revised review date drew closer, Sanofi said on December 15 that the FDA had cautioned the company not to expect further direction on the application until March 2026.
With no decision anticipated in the near term, Sanofi’s R&D chief Houman Ashrafian, said in a December 24 statement that last week’s complete response letter represented a notable shift away from the guidance the agency had previously given the company under those circumstances.
Ashrafian said the company was saddened by the FDA’s move, emphasizing that slowing disability progression remains a significant unmet need in multiple sclerosis and noting that tolebrutinib had previously received breakthrough therapy status from the agency in recognition of its work to meet this gap in the market.
He added that the FDA should also consider guidance from scientific experts, doctorsand patients to ensure all perspectives are taken into account, while reiterating Sanofi’s commitment to continuing discussions with regulators to identify a path forward for tolebrutinib and ultimately support the MS community at large. The firm did not provide additional detail on why the FDA reversed its position on the application.
The decision marks another hurdle for tolebrutinib, a drug Sanofi gained through its $3.7 billion acquisition of Principia Biopharma in 2021. In 2022, the program ran into further trouble when the FDA imposed a partial hold on several late-stage trials while it assessed reports of liver-related safety concerns linked to the treatment.
Sanofi disclosed a further year later, in 2023, that tolebrutinib missed its primary goals in two of three late-stage multiple sclerosis trials. Despite those setbacks, the company said it would continue pursuing regulatory clearance in non-relapsing secondary progressive MS, citing positive results in that specific patient population.
The hit-and-miss trial outcomes narrowed the drug’s overall development prospects. As a result, Sanofi earlier this year dropped plans to pursue tolebrutinib for relapsing MS and removed that indication from its pipeline.
These twin rejections by the FDA underscore the complexity of drug approval in areas with high unmet medical need, such as progressive neurological diseases and rare hormonal disorders. For Sanofi, the setback with tolebrutinib may prompt a reevaluation of its clinical development strategy, particularly in how to demonstrate clear benefit while addressing safety concerns that regulators have repeatedly flagged.
For Corcept, the FDA’s complete response letter suggests that additional clinical evidence or new trials may be required before relacorilant can be reconsidered. While the company’s existing drug Korlym remains on the market for other indications, relacorilant’s rejection may delay Corcept’s hopes of expanding into new therapeutic areas and could require significant investment in follow‑up studies.
