Corcept Therapeutics has received an FDA Complete Response Letter for relacorilant in hypertension secondary to hypercortisolism. Learn what the CRL means, how GRACE and GRADIENT trial results influenced the decision, and the status of relacorilant’s ongoing oncology programs.
Written By: Pharmacally Medical News Desk
On 31 December 2025, Corcept Therapeutics announced that the US Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for its New Drug Application (NDA) for relacorilant as a treatment for patients with hypertension secondary to hypercortisolism (Cushing’s syndrome).
In the CRL, the FDA acknowledged that the pivotal Phase 3 GRACE trial achieved its primary endpoint and that data from the Phase 3 GRADIENT study provided supportive evidence. However, the agency concluded that it could not determine a favorable benefit–risk profile for this indication without additional evidence of effectiveness.
Corcept stated that it plans to meet with the FDA to better understand the additional data requirements and define a possible path toward resubmission.
What is Relacorilant
Relacorilant is an oral selective glucocorticoid receptor modulator designed to reduce the harmful effects of excess cortisol while minimizing hormone-related side effects that can occur with less selective therapies. The drug has received orphan drug designation from both the FDA and the European Commission for the treatment of hypercortisolism, as well as from the European Commission for ovarian cancer.
Key clinical evidence behind the FDA decision
GRACE Trial (NCT03697109)
The Phase 3 GRACE trial evaluated Relacorilant in patients with endogenous hypercortisolism. The study demonstrated meaningful improvements in blood pressure and metabolic control and met its randomized-withdrawal primary endpoint. Safety findings were consistent with expectations, and these data formed the pivotal evidence base for the NDA.
GRADIENT Trial (NCT04308590)
The Phase 3 GRADIENT trial studied Relacorilant in patients with adrenal Cushing’s syndrome. Although the trial showed favorable clinical trends, it did not meet its primary endpoint of improving systolic blood pressure compared with placebo.
As a result, the FDA considered GRADIENT supportive but not sufficient to confirm relacorilant’s effectiveness in hypertension secondary to hypercortisolism. In the CRL, the agency indicated that more evidence is needed before approval can be considered.
Corcept’s Chief Executive Officer, Joseph K. Belanoff, MD, noted that the company was surprised and disappointed by the decision, while reaffirming its commitment to patients living with hypercortisolism.
In the near term, Corcept plans to meet with the FDA to review the CRL in detail and understand the additional evidence requested. Based on that discussion, the company may consider new analyses or further clinical work. Corcept will update its plans and timelines once the regulatory path forward becomes clearer.
Oncology development remains on track
From a broader portfolio perspective, Relacorilant remains an important asset in Corcept’s endocrine and oncology pipeline.
The CRL applies only to Relacorilant’s NDA for hypertension secondary to hypercortisolism and does not affect the company’s oncology programs. Relacorilant remains under FDA review as a potential treatment for platinum-resistant ovarian cancer, with a Prescription Drug User Fee Act (PDUFA) decision date set for July 11, 2026. Corcept has also submitted a Marketing Authorization Application to the European Medicines Agency for the same indication. The company noted that oncology development activities continue as planned.
If approved in oncology, relacorilant could still become a commercial product even if its endocrine indication requires additional time or studies.
Hypercortisolism: a brief overview
Hypercortisolism, commonly seen in Cushing’s syndrome, results from prolonged exposure to excessive cortisol. Patients often experience central weight gain, facial rounding, fragile skin with purple striae, muscle weakness, hypertension, diabetes, and higher risks of infections and blood clots.
Surgery to remove the underlying tumor is the preferred first-line treatment, but not all patients are cured or eligible for surgery. In such cases, medical therapies that reduce cortisol levels or block its effects play an important role.
Approved options in the United States include Korlym (mifepristone) for hyperglycemia secondary to endogenous Cushing’s syndrome. Despite available treatments, some patients continue to have inadequate disease control or treatment-related tolerability issues, underscoring the need for additional therapeutic options. Relacorilant has been developed to help address this gap as a selective glucocorticoid receptor modulator.
References
Corcept Receives Complete Response Letter for Relacorilant as a Treatment for Patients with Hypercortisolism, 31 December 2025, https://ir.corcept.com/news-releases/news-release-details/corcept-receives-complete-response-letter-relacorilant-treatment
A Study of the Efficacy and Safety of Relacorilant in Patients with Cortisol-Secreting Adrenal Adenomas (GRADIENT), ClinicalTrials.gov ID NCT04308590, https://clinicaltrials.gov/study/NCT04308590
A Study of the Efficacy and Safety of Relacorilant in Patients with Endogenous Cushing Syndrome (GRACE), ClinicalTrials.gov ID NCT03697109, https://clinicaltrials.gov/study/NCT03697109
Relacorilant Fails to Meet Primary Endpoint in GRADIENT Trial for Cushing’s Syndrome, https://trial.medpath.com/news/18d1a07c597fa0f8/corcept-s-relacorilant-gradient-trial-misses-primary-endpoint