Year-End FDA Rejections Deliver Harsh Reality Check to Sanofi and Corcept

The final days of 2025 delivered unwelcome surprises to two pharmaceutical companies as the FDA issued complete response letters rejecting drug applications from both Sanofi and Corcept Therapeutics. These unexpected regulatory setbacks underscore the unpredictable nature of drug approval processes and highlight how even promising therapies with strong clinical data can face regulatory hurdles.

Sanofi received its rejection on December 24, when the FDA declined to approve tolebrutinib for non-relapsing secondary progressive multiple sclerosis (nrSPMS). The decision came as a particular shock given the drug's previous breakthrough therapy designation and the agency's earlier guidance suggesting a delayed but eventual decision. Corcept Therapeutics followed with its own devastating news on December 31, as the FDA rejected relacorilant for Cushing's syndrome, sending the company's stock plummeting 50% in a single trading session.

Tolebrutinib's Troubled Journey

Sanofi's tolebrutinib represents a significant investment in multiple sclerosis treatment, acquired as part of the company's $3.7 billion purchase of Principia Biopharma in 2021. The oral BTK inhibitor was designed to address disability progression in MS patients, a critical unmet medical need where treatment options remain limited.

The drug's development path has been marked by setbacks. In 2022, the FDA placed late-stage studies under partial clinical hold due to reports of drug-induced liver injury. Despite these safety concerns, Sanofi pressed forward after resolving the hold, banking on positive results from one of three phase 3 trials in nrSPMS.

The recent rejection represents what Sanofi called a "significant and meaningful change in direction" from previous FDA feedback. The company had received priority review status in March 2025, with an initial decision deadline of September 28. However, the submission of additional analyses during review constituted a major amendment, pushing the decision to December 28, and ultimately to the rejection announced on Christmas Eve.

Sanofi's head of R&D, Houman Ashrafian, expressed disappointment with the FDA's decision, emphasizing that "disability progression remains a large unmet medical need in MS." The company maintains its commitment to finding a path forward for the drug, though the regulatory landscape has clearly become more challenging than anticipated.

Corcept's Cushing's Syndrome Setback

Corcept Therapeutics faced an equally devastating blow with the FDA's rejection of relacorilant for Cushing's syndrome. The company had built significant expectations around this application, supported by positive results from the pivotal Grace trial where the drug met its primary endpoint.

The FDA acknowledged that Corcept's Grace trial met its primary endpoint and that confirmatory evidence existed from the company's Gradient trial. However, the agency concluded it could not arrive at a favorable benefit-risk assessment without additional evidence of effectiveness. This decision surprised Corcept management, who had not anticipated the need for further clinical data.

The market reaction was swift and severe. Corcept's stock price collapsed from $70.20 to $34.80, wiping out approximately $4 billion in market value. The dramatic selloff reflects investor concerns about the time and resources required to generate additional clinical evidence, potentially delaying market entry by years.

CEO Joseph Belanoff expressed confidence in finding a path forward, stating the company would meet with the FDA "as soon as possible to discuss the best path forward." However, analysts have significantly reduced price targets, with Truist Securities lowering its target from $135 to $50, citing concerns about the regulatory outlook.

Broader Regulatory Implications

These rejections highlight evolving FDA standards and the agency's increasingly rigorous approach to benefit-risk assessments. Both companies had reasonable expectations of approval based on their clinical data and previous regulatory interactions, yet both encountered unexpected resistance.

The timing of these decisions, during the holiday period, adds an element of unfortunate symbolism to what represents genuine setbacks for patients awaiting new treatment options. For MS patients with progressive disease and individuals suffering from Cushing's syndrome, these rejections mean continued reliance on existing therapies with known limitations.

The pharmaceutical industry continues to grapple with regulatory unpredictability, where even drugs with breakthrough designations and positive trial results can face rejection. These cases serve as reminders that clinical success does not guarantee regulatory approval, and that companies must prepare for multiple scenarios throughout the development process.

Both Sanofi and Corcept now face the challenge of determining whether to invest additional resources in addressing FDA concerns or to redirect efforts toward other pipeline opportunities. Their decisions will likely influence how other companies approach similar regulatory challenges in an increasingly complex approval environment.