FDA rejects relacorilant for Cushing’s-related high blood pressure
Agency needs more evidence of treatment's effectiveness and safety: Corcept
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The U.S. Food and Drug Administration (FDA) has declined to approve relacorilant, an experimental oral therapy for patients with Cushing’s syndrome experiencing high blood pressure. In a complete response letter, the agency stated that current data do not yet conclusively show that the treatment’s benefits outweigh its risks.
The decision comes as a setback for developer Corcept Therapeutics, which had sought approval for the drug to treat endogenous Cushing’s syndrome, including Cushing’s disease. Corcept now plans to meet with federal regulators to determine what additional evidence or trials may be needed to bring the therapy to market.
“We are surprised and disappointed by this outcome,” Joseph K. Belanoff, MD, CEO of Corcept, said in a company press release. He added that the company remains committed to the treatment and will discuss the “best path forward” with the FDA as soon as possible.
Understanding endogenous Cushing’s syndrome
Cushing’s syndrome broadly refers to health issues that are driven by abnormally high levels of the stress hormone cortisol. In endogenous Cushing’s, cortisol levels are high due to an issue within the body (as opposed to exogenous Cushing’s, where cortisol levels are high as a side effect of a medication).
The most common form of endogenous Cushing’s syndrome is Cushing’s disease, which is caused by a tumor in the brain’s pituitary gland, leading to abnormal hormone signaling that ultimately triggers excessive cortisol production.
Relacorilant is an oral therapy designed to block cortisol signaling by modulating the activity of cellular receptors that respond to cortisol. By targeting these receptors, the therapy essentially aims to reduce cortisol activity in the body, thereby easing Cushing’s symptoms.
Corcept applied for FDA approval of relacorilant in late 2024. The company’s application was based largely on data from the Phase 3 GRACE clinical trial (NCT03697109), which tested the therapy in people with Cushing’s who had diabetes or high blood pressure. Results showed that relacorilant helped lower blood pressure, decreased blood sugar levels, and promoted weight loss.
Corcept’s application was also supported by data from another Phase 3 trial called GRADIENT (NCT04308590), as well as data from an earlier Phase 2 study (NCT02804750) and an extension study (NCT03604198) that tracked long-term outcomes in patients who had completed prior studies. Data from the extension study showed that relacorilant led to sustained reductions in blood pressure and blood sugar levels. The therapy was generally well tolerated in clinical testing, with common side effects including pain, headache, swelling, and nausea.
In its complete response letter, the FDA acknowledged that GRACE met its main goal and that GRADIENT provided confirmatory evidence. However, the agency stated it was unable to definitively conclude that the therapy’s benefit-to-risk profile is favorable without additional evidence demonstrating its effectiveness, according to Corcept.
“Our commitment to patients suffering from the effects of hypercortisolism [high cortisol levels] is unwavering. I am confident we will find a way to get relacorilant to the patients it could help,” Belanoff said.
Relacorilant is also currently under review by the FDA as a potential treatment for platinum-resistant ovarian cancer.
