FDA declines to approve Corcept's rare disorder drug
Joe Belanoff, Corcept's chief executive.
As the celebrations for the end of 2025 gathered pace, the FDA delivered a year-end blow to Corcept Therapeutics with a decision not to approve relacorilant, a drug for a rare hormonal disorder that causes high blood pressure.
In a complete response letter (CRL), the US regulator said it would not be able to approve relacorilant for patients with hypertension secondary to hypercortisolism – also known as Cushing's syndrome – without additional evidence of its efficacy.
In Cushing's, high levels of cortisol, a stress hormone, lead to weight gain in the torso and face with thin limbs, high blood pressure, muscle weakness, high blood sugar (hyperglycaemia), and other symptoms like fatigue and bruising.
Relacorilant (previously known as CORT-125134) is a selective glucocorticoid receptor (GR) antagonist that was tested in the phase 3 GRACE trial in patients with hypercortisolism and hypertension and/or hyperglycaemia, showing significant improvements in blood pressure compared to placebo and meeting the primary endpoint of loss of hypertension control.
The marketing application was supported by data from the GRADIENT study, which missed its primary endpoint of improving systolic blood pressure in hypercortisolism patients compared to placebo, but did show a benefit over control on secondary markers like blood sugar, weight, and body composition compared to baseline.
When it filed for approval of relacorilant with the FDA in December 2024, Corcept said the drug had the potential to become a new standard of care for Cushing's syndrome, which is currently treated using medicines to reduce cortisol production.
"We are surprised and disappointed by this outcome," said Joe Belanoff, Corcept's chief executive.
"Our commitment to patients suffering from the effects of hypercortisolism is unwavering," he added. "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."
Corcept already markets one drug for Cushing's – Korlym (mifepristone) – which is used to reduce blood sugar associated with hypercortisolism and has been on sale since 2012. Along with a self-marketed generic version of the drug, sales are due to reach upwards of $800 million in 2025, although generics have started to reach the market, and Corcept is looking to new sources of revenue.
The setback for relacorilant in Cushing's is therefore a blow – particularly if the FDA insists on a new trial, which could delay the programme significantly – although, Corcept has broader aspirations for the drug.
Last year, for example, relacorilant hit the mark in the phase 3 ROSELLA study in platinum-resistant ovarian cancer, prompting a US filing that has an 11th July action date by the FDA.
