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Relacorilant NDA Submitted to FDA for Treatment of Endogenous Hypercortisolism
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Key Takeaways
- Relacorilant shows promise in treating hypercortisolism, with significant symptom improvement and no serious adverse events in phase 3 trials.
- The drug's efficacy and safety profile could establish it as the standard of care for hypercortisolism.
Backed by positive results in multiple clinical trials, a new drug application (NDA) has been submitted for relacorilant for consideration by the FDA.
A new drug application (NDA) to the FDA for relacorilant (Corcept Therapeutics), a proprietary, selective cortisol modulator, for the treatment of patients with endogenous hypercortisolism, also called Cushing syndrome.1 The submission of the NDA is based on positive results from the phase 3 GRACE trial (NCT03697109) and confirmatory data from the phase 3 GRADIENT trial (NCT04308590), and it’s long-term extension studies, which collectively indicated improvements in a wide range of signs and symptoms of hypercortisolism in patients treated with relacorilant.1,2,3
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“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,” Joseph Belanoff, MD, chief executive officer of Corcept, said in the news release. “We are optimistic that relacorilant will be of great benefit to [patients with hypercortisolism].”1
In the GRACE trial, patients met the primary end point of loss of blood pressure control in the randomized withdrawal phase in patients receiving relacorilant compared with placebo. Importantly, relacorilant was well-tolerated in each phase of GRACE. Overall, patients demonstrated statistically significant improvements in hypertension, hyperglycemia, and other symptoms that patients with hypercortisolism often experience.4
“The data from GRACE make a compelling case for the use of relacorilant in patients with endogenous hypercortisolism,” principal investigator of the GRACE trial Rosario Pivonello, MD, PhD, said in a statement upon the release of the trial results. “That patients experienced clinically significant improvements in hypertension, hyperglycemia, and the other signs and symptoms of Cushing syndrome, without significant safety burden, is greatly encouraging for physicians and the patients they seek to help.”4
Furthermore, in the collection of studies backing the NDA, there were no instances of serious adverse events (AEs) such as drug-induced adrenal insufficiency, hypokalemia, or QT prolongation, which can arise in patients taking currently approved medications for hypercortisolism. In addition, there were no AEs associated with activity at the progesterone receptor, such as vaginal bleeding or endometrial thickening.1
Hypercortisolism can be caused by excessive activity of the hormone cortisol. Many patients will experience the syndrome as one or more manifestations of hypertension, difficult-to-control type 2 diabetes alongside elevated blood sugar, severe fatigue, or central obesity. Other common effects include depression, irritability, anxiety, and cognitive disturbances. If not treated effectively, hypercortisolism could be fatal.1
The NDA submission marks another step in the recent development of treatments for Cushing syndrome. Last year, the FDA granted an orphan drug designation for clofutriben (Sparrow Pharmaceuticals), a potent selective HSD-1 inhibitor, for the treatment of hypercortisolism, a novel approach to treating the condition. It could also offer a new treatment option for patients with autonomous cortisol secretion, a milder but more dominant form of hypercortisolism.5
REFERENCES
1. Corcept Therapeutics. Corcept submits new drug application for relacorilant as a treatment for patients with hypercortisolism. BusinessWire. News Release. Released December 30, 2024. Accessed January 3, 2025. https://www.businesswire.com/news/home/20241230947567/en/Corcept-Submits-New-Drug-Application-for-Relacorilant-as-a-Treatment-for-Patients-With-Hypercortisolism
2. ClinicalTrials.gov. A study of the efficacy and safety of relacorilant in patients with endogenous Cushing syndrome (GRACE). National Library of Medicine. Last updated August 29, 2024. Accessed January 3, 2025. https://clinicaltrials.gov/study/NCT03697109
3. ClinicalTrials.gov. Efficacy and safety of relacorilant in patients with cortisol-secreting adrenal adenomas (GRADIENT). National Library of Medicine. Last updated November 19, 2024. Accessed January 3, 2025. https://clinicaltrials.gov/study/NCT04308590
4. Corcept Therapeutics. Corcept announces primary end point met in pivotal phase 3 GRACE trial of relacorilant in patients with hypercortisolism (Cushing’s syndrome). News Release. Released May 28, 2024. Accessed January 3, 2025. https://ir.corcept.com/news-releases/news-release-details/corcept-announces-primary-endpoint-met-pivotal-phase-3-grace
5. Ferruggia K. Clofutriben receives FDA orphan drug designation to treat endogenous Cushing syndrome. Pharmacy Times. Published November 4, 2024. Accessed January 3, 2025. https://www.pharmacytimes.com/view/clofutriben-receives-fda-orphan-drug-designation-to-treat-endogenous-cushing-syndrome
