Corcept’s NDA for Cushing syndrome drug relacorilant met with FDA’s CRL

Edited by Robert McTiernan··3 min read

Corcept Therapeutics (NASDAQ: CORT) revealed that its New Drug Application (NDA) filing for relacorilant as a treatment for hypertension secondary to endogenous hypercortisolism has been met with a Complete Response Letter (CRL) from the US FDA. Within the CRL, the FDA acknowledged that Corcept’s pivotal GRACE trial met its primary endpoint and that data from the Phase 3 GRADIENT trial provided supportive evidence. However, the FDA concluded it “could not arrive at a favorable benefit-risk assessment… without Corcept providing additional evidence of effectiveness”, necessitating further data before approval could be considered.

Corcept’s CEO, Joseph K. Belanoff, MD, described the outcome as “surprising and disappointing” and reiterated the company’s commitment to patients with hypercortisolism. Corcept plans to meet with the FDA promptly to discuss potential next steps and pathways to address the agency’s concerns.

About relacorilant

Relacorilant is a highly selective, non-steroidal glucocorticoid receptor (GR) antagonist developed by Corcept. Its primary clinical focus is the treatment of hypertension secondary to endogenous hypercortisolism (also known as Cushing syndrome) and certain solid tumors, including ovarian cancer. Relacorilant’s mechanism of action centers on competitive antagonism of the GR, blocking the effects of excess cortisol without significant off-target activity, notably lacking affinity for the progesterone receptor—a key differentiator from the class-defining agent mifepristone. This selectivity is hypothesized to yield a more favorable safety profile, particularly regarding reproductive and metabolic adverse effects.

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The drug retains orphan drug designations for hypercortisolism and ovarian cancer in both the US and EU. The FDA has assigned a PDUFA decision date of July 11, 2026, for relacorilant in combination with nab-paclitaxel for platinum-resistant ovarian cancer, and Corcept has also filed a Marketing Authorization Application with the EMA for that indication.

The CRL for Cushing syndrome does not bar future approval but signals that Corcept will likely need to generate additional evidence — potentially new or expanded analyses — to satisfy the FDA’s effectiveness criteria for the hypercortisolism indication.

Research context

The therapeutic landscape for Cushing syndrome us rapidly changing, with several agents under development or recently approved targeting various points in the hypothalamic-pituitary-adrenal (HPA) axis or acting directly on cortisol synthesis and action. The most notable recent advances include new steroidogenesis inhibitors, selective GR antagonists, pituitary-directed therapies, and agents with novel mechanisms such as ACTH antagonism and epigenetic modulation. A selection of key molecules in the field include:

  • Osilodrostat (LCI699) from Novartis/Recordati, an oral inhibitor of 11β-hydroxylase (CYP11B1) that blocks the final step of cortisol synthesis in the adrenal gland. The molecule was approved in the US (Cushing’s disease) in 2020 followed by the EU and Japan (endogenous Cushing’s syndrome).
  • Levoketoconazole, developed by Xeris Biopharma, is a stereoisomer of ketoconazole that inhibits multiple enzymes in adrenal steroidogenesis. The molecule gained FDA approval in 2021.
  • Atumelnant (CRN04894) from Crinetics Pharmaceuticals is a potential first-in-class oral ACTH receptor (MC2R) antagonist that blocks ACTH signaling at the adrenal cortex. The molecule is in Phase 2/3 trials for ACTH-dependent Cushing’s syndrome and congenital adrenal hyperplasia (Crinetics pipeline10, Crinetics press release11).
  • SPI-62 (clofutriben), from Sparrow Pharmaceuticals, is a selective HSD-1 (11β-hydroxysteroid dehydrogenase type 1) inhibitor, reducing local cortisol regeneration in tissues. The molecule has entered Phase 2 trials for Cushing syndrome and other glucocorticoid excess states.