FDA Issues Complete Response Letter for Corcept's Relacorilant in Hypercortisolism Treatment
Key Insights
The FDA issued a Complete Response Letter for Corcept Therapeutics' relacorilant, rejecting approval for treating hypertension (search) secondary to hypercortisolism (search) despite acknowledging that the pivotal GRACE trial met its primary endpoint.
The Agency concluded it could not arrive at a favorable benefit-risk assessment without additional evidence of effectiveness, even though data from the GRADIENT trial provided confirmatory evidence.
Corcept's CEO expressed surprise and disappointment at the outcome, stating the company will meet with the FDA as soon as possible to discuss the best path forward for getting relacorilant to patients.
The U.S. Food and Drug Administration has issued a Complete Response Letter (CRL) for Corcept Therapeutics' relacorilant, rejecting approval of the selective glucocorticoid receptor (search) antagonist as a treatment for patients with hypertension (search) secondary to hypercortisolism (search). The decision comes despite the FDA's acknowledgment that Corcept's pivotal GRACE trial met its primary endpoint and that data from the company's GRADIENT trial provided confirmatory evidence.
The regulatory setback represents a significant blow to Corcept Therapeutics (NASDAQ: CORT), which had been targeting a PDUFA date of December 30, 2025, for this financially pivotal milestone. The approval was expected to help the company reduce its sole reliance on Korlym for revenue generation and transition toward becoming a multi-asset profitability company.
Clinical Trial Results and FDA Assessment
Relacorilant's New Drug Application was primarily supported by data from two Phase 3 trials: GRACE and GRADIENT. In the GRACE trial, which enrolled patients with endogenous Cushing's syndrome (search) of all etiologies, relacorilant met its primary endpoint where patients switched to placebo had a significantly higher risk of losing hypertension (search) control.
However, the GRADIENT trial, which enrolled patients with adrenal-origin Cushing's syndrome, failed to meet its primary endpoint to reduce mean systolic blood pressure. This mixed efficacy profile may have contributed to the FDA's concerns, as the NDA indication covers all endogenous Cushing syndrome patients, including those with adrenal adenoma.
Despite acknowledging the positive results from both trials, the FDA concluded it could not arrive at a favorable benefit-risk assessment for relacorilant without additional evidence of effectiveness from Corcept.
Company Response and Next Steps
"We are surprised and disappointed by this outcome," said Joseph K. Belanoff, MD, Corcept's Chief Executive Officer. "Our commitment to patients suffering from the effects of hypercortisolism (search) is unwavering. I am confident we will find a way to get relacorilant to the patients it could help. We will meet with the FDA as soon as possible to discuss the best path forward."
The rejection significantly impacts Corcept's near-term prospects, as the company has no other pre-registration drug expected to reach approval in the next 3-5 years. This leaves Corcept heavily dependent on its existing approved medication, Korlym, which was introduced in February 2012 as the first FDA-approved treatment for patients with endogenous hypercortisolism (search).
Broader Pipeline Implications
Relacorilant remains in development for other indications, including ovarian cancer (search). The FDA has assigned a PDUFA date of July 11, 2026, for relacorilant as a treatment for patients with platinum-resistant ovarian cancer (search). Corcept has also recently submitted a Marketing Authorization Application to the European Medicines Agency (search) for relacorilant to treat patients with platinum-resistant ovarian cancer.
The oral therapy is designed as a selective glucocorticoid receptor (search) antagonist that modulates cortisol activity by binding to the GR without affecting the body's other hormone receptors. Relacorilant has received orphan drug designation from both the FDA and European Commission for hypercortisolism (search) treatment, and from the European Commission for ovarian cancer (search) treatment.
Despite the regulatory setback, Corcept maintains a strong financial position with a market capitalization of $8.9 billion and no long-term debt. The company has been able to fund its pipeline development through increased revenue from Korlym commercialization, avoiding the need for dilutive equity financing.