Corcept Therapeutics Incorporated (NASDAQ: CORT) has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for relacorilant, its proprietary selective cortisol modulator, to treat patients with endogenous hypercortisolism, commonly known as Cushing's syndrome.
The NDA submission, announced on December 30, 2024, represents a significant milestone in the company's development of treatments for this serious endocrine disorder. The application is based on positive results from multiple clinical studies, including the pivotal Phase 3 GRACE trial and confirmatory evidence from the Phase 3 GRADIENT study, long-term extension studies, and a Phase 2 study in hypercortisolism.
Clinical Evidence Supporting the Application
Patients who received relacorilant in these studies experienced improvements across a wide array of hypercortisolism's signs and symptoms. The drug demonstrated an acceptable safety profile throughout the clinical program.
Notably, relacorilant showed none of the serious adverse events that can occur with currently approved medications for Cushing's syndrome. There were no instances of drug-induced adrenal insufficiency, hypokalemia, or QT prolongation—all potentially serious complications associated with existing treatments. Additionally, the drug showed no adverse events associated with activity at the progesterone receptor, such as endometrial thickening or vaginal bleeding.
"Relacorilant's combination of efficacy and safety give it the potential to become the standard of care for the medical treatment of patients with hypercortisolism," said Joseph Belanoff, MD, Corcept's Chief Executive Officer. "Our commitment to the health of patients with hypercortisolism is unwavering. We are optimistic that relacorilant will be of great benefit to them."
Understanding Relacorilant's Mechanism
Relacorilant is a selective cortisol modulator that binds specifically to the glucocorticoid receptor without affecting the body's other hormone receptors. This selectivity is believed to contribute to its favorable safety profile compared to existing treatments.
Beyond Cushing's syndrome, Corcept is investigating relacorilant for several other serious conditions, including ovarian, adrenal, and prostate cancer. The drug has received orphan drug designation for Cushing's syndrome treatment in both the United States and the European Union, which provides certain development incentives and potential market exclusivity.
The Burden of Cushing's Syndrome
Hypercortisolism results from excessive activity of the hormone cortisol. While symptoms can vary between patients, most experience one or more of the following manifestations:
- Hypertension
- Central obesity
- Elevated blood sugar and difficult-to-control type 2 diabetes
- Severe fatigue and muscle weakness
- Irritability, anxiety, depression, and cognitive disturbances
If left untreated effectively, hypercortisolism can affect every organ system and may be lethal. The condition represents a significant unmet medical need, with current treatments often carrying substantial side effect burdens.
Corcept's Focus on Cortisol Modulation
For over 25 years, Corcept has focused on cortisol modulation and its potential to treat patients with various serious disorders. This research has led to the discovery of more than 1,000 proprietary selective cortisol modulators.
The company currently markets Korlym® (mifepristone), which was approved by the FDA in February 2012 as the first medication for treating patients with endogenous hypercortisolism. Korlym has been a consistent revenue driver for Corcept, with sales increasing 42.1% year over year to $493.2 million in the first nine months of 2024, according to the company's financial reports.
Regulatory Timeline and Market Implications
Following the NDA submission, the FDA will review the application and determine whether to accept it for filing. If accepted, the agency will establish a Prescription Drug User Fee Act (PDUFA) date, which would set a target timeline for the FDA's decision.
Industry analysts note that if approved, relacorilant could significantly expand Corcept's market position in the treatment of Cushing's syndrome. The drug's improved safety profile compared to existing options could drive broader adoption among endocrinologists and potentially capture a larger share of the addressable market.
"The successful development and potential approval for relacorilant should help Corcept address a broader patient population," noted one market analyst following the announcement.
Looking Ahead
The FDA's review process typically takes approximately 10-12 months for standard reviews. If approved, relacorilant would become Corcept's second commercial product for Cushing's syndrome, potentially strengthening the company's position in this therapeutic area.
On March 3, 2025, Corcept announced that the FDA had officially filed the NDA submission for relacorilant and assigned a Prescription Drug User Fee Act (PDUFA) target action date of December 30, 2025, setting a clear timeline for the potential approval decision.
"The FDA's acceptance of our New Drug Application takes us another step closer to bringing relacorilant to patients with hypercortisolism," said Dr. Belanoff following the FDA's filing of the application. "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."
