FDA Accepts NDA for Relacorilant for Endogenous Hypercortisolism

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for relacorilant, a selective cortisol modulator targeted for the treatment of patients with endogenous hypercortisolism (Cushing’s syndrome).¹

Announced by Corcept Therapeutics Incorporated, on March 3, 2025, the regulatory agency has assigned a Prescription Drug User Fee Act (PDUFA) target action date of December 30, 2025.

“The FDA’s acceptance of our New Drug Application takes us another step closer to bringing relacorilant to patients with hypercortisolism,” said Joseph Belanoff, MD, chief executive officer of Corcept.¹

Excessive activity of cortisol can lead to a variety of manifestations, including hypertension, central obesity, elevated blood sugar, and difficult-to-control type 2 diabetes (T2D). Patients with hypercortisolism often experience symptoms such as irritability, anxiety, and depression. Without effective treatment, hypercortisolism can impact every organ system and lead to considerable mortality risk.²

Relacorilant is a selective cortisol modulator that binds to only the glucocorticoid receptor, not the body's other hormone receptors. The FDA has granted relacorilant Orphan Drug Designation for the treatment of Cushing’s syndrome. Its NDA was based on positive results from the pivotal GRACE trial, and confirmatory evidence from the Phase 3 long-term extension GRADIENT trial and a Phase 2 trial in hypercortisolism.¹

The Phase 3 GRACE trial was a 2-part clinical trial, with the first part being an open-label phase where 152 patients with Cushing’s syndrome and either hypertension, hyperglycemia, or both received relacorilant for 22 weeks.³

In the first portion of the trial, 63% of patients with hypertension met the study’s response criteria, with use associated with rapid and sustained improvements for both systolic (mean reduction, 7.9 mmHg; P <.0001) and diastolic (mean reduction, 5.4 mmHg; P <.0001) at 22 weeks. Among those with hyperglycemia, all patients achieved clinically meaningful and statistically significant improvements in glucose metabolism, with 50% meeting the study’s response criteria.

The second part of the trial consisted as a double-blind, randomized, withdrawal period, with the maintenance of blood pressure control serving as the primary outcome of interest. In this portion of the trial, patients who met response criteria in the first part of the trial were randomized 1:1 to continue relacorilant or switch to placebo therapy for 12 weeks.

According to data presented at the Heart in Diabetes (HiD) meeting, results indicated loss of blood pressure control was 83% less likely to occur among patients relieving relacorilant compared to placebo (OR, 0.17; P = .02). Investigators pointed out similar blood pressure trends to part 1 of the trial, with results favoring use of relacorilant over placebo therapy for 24-hour systolic and diastolic blood pressure, daytime systolic and diastolic blood pressure, and nighttime systolic and diastolic blood pressure.

Relacorilant was tolerable without instances of drug-induced adrenal insufficiency, hypokalemia or QT prolongation. Investigators identified no adverse events associated with activity at the progesterone receptor, including endometrial thickening or vaginal bleeding.¹

“Relacorilant’s combination of efficacy and safety gives it the potential to become the new standard of care for patients struggling with the devastating impact of this disease,” Belanoff added.¹

References

1. FDA files Corcept’s New Drug Application for relacorilant as treatment for patients with hypercortisolism. Corcept Therapeutics, Incorporated. March 3, 2025. Accessed March 3, 2025. https://ir.corcept.com/news-releases/news-release-details/fda-files-corcepts-new-drug-application-relacorilant-treatment.

2. Uwaifo GI, Hura DE. Hypercortisolism. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551526/

3. Campbell P. Full grace results shed further light on effects of relacorilant in hypercortisolism. HCP Live. July 2, 2024. Accessed March 3, 2025. https://www.hcplive.com/view/full-grace-results-shed-further-light-on-effects-of-relacorilant-in-hypercortisolism.