Relacorilant and Cardiometabolic Outcomes

Posted on September 25, 2025 by MaryO

New data on relacorilant (Corcept Therapeutics), a selective glucocorticoid receptor modulator, revealed several cardiometabolic benefits for patients with hypercortisolism.

Researchers presented results from the GRACE and GRADIENT trials, which assessed relacorilant in adults with hypercortisolism. GRACE was an open-label trial that enrolled adults with endogenous hypercortisolism, whereas GRADIENT included those with adrenal hypercortisolism and randomly assigned participants to relacorilant or placebo.

Both trials demonstrated similar reductions in body weight. The relacorilant group in GRADIENT had a 3.6 kg reduction in body weight, and adults in GRACE reduced their body weight by 3.3 kg at 22 weeks.

“Relacorilant may improve many of the common features of hypercortisolism, which may provide a holistic benefit to our patients,” Oksana Hamidi, DO, MSCS, study investigator and associate professor in the division of endocrinology at UT Southwestern Medical Center, told Healio | Endocrine Today. “An interesting observation was that relacorilant can lead to weight loss, and that weight loss is mostly fat mass, with lean mass being preserved or even increasing. The ability to maintain muscle is particularly important for our patients.”

In a cardiometabolic analysis, adults with hypertension receiving relacorilant had greater reductions in both systolic and diastolic blood pressure compared with placebo. For adults with hyperglycemia at baseline, the relacorilant group had greater declines in fasting glucose and glucose area under the curve.

Corin Badiu, MD, study investigator, professor of endocrinology and head of the department of endocrinology IV in the National Institute of Endocrinology and “C.Davila” University of Medicine and Pharmacy in Bucharest, Romania, and fellow of the Romanian Academy of Medical Sciences, said the benefits of relacorilant may extend into additional areas that could be studied in the future.

“Apart from metabolic and cardiovascular improvements, we expect long-term improvements in bone mass, liver steatosis, mood, sleep and other behavioral aspects [that] are disturbed in hypercortisolism,” Badiu told Healio | Endocrine Today.

Irina Bancos, MD, MSc, professor of medicine in the division of endocrinology, metabolism and nutrition at Mayo Clinic, said relacorilant could provide benefits similar to mifepristone (Korlym, Corcept Therapeutics) for patients with hypercortisolism, but with fewer adverse events related to progesterone health. Bancos was not involved with the trial.

“Why is there a need for another medication in the same class by the same company? The major reason is to achieve the same metabolic impact as far as weight loss and improvement of hyperglycemia … but also to decrease the side effects,” Bancos told Healio | Endocrine Today.

From https://www.healio.com/news/endocrinology/20250912/promising-new-data-could-change-treatment-landscape-for-some-rare-diseases?utm_source=selligent&utm_medium=email&utm_campaign=20250920ENDO&utm_content=20250920ENDO

Filed under: adrenal, Clinical trials, Cushing's, pituitary, Treatments | Tagged: , , , , | Leave a comment »

Corcept’s relacorilant GRADIENT trial misses primary endpoint

Posted on November 6, 2024 by MaryO

Corcept Therapeutics has shared some results from its Phase III GRADIENT trial for relacorilant – its experimental treatment for Cushing’s syndrome caused by adrenal gland pathology.

The trial will be used alongside data from the earlier GRACE trial to support the company’s new drug application (NDA) submission this quarter. However, it missed its primary endpoint.

The complete results of the company’s GRADIENT trial will be presented at a medical conference next year, but current results – released on 30 October – demonstrate that there was no statistically significant difference in hypertension in relacorilant and placebo patients.

The randomised double-blind trial included 137 patients across sites in the US, Europe and Israel. Over 22 weeks, half of the patients received relacorilant while the other half received a placebo.

The trial’s primary endpoint was the improvement in systolic blood pressure (SBP) compared to placebo. Its secondary endpoints were concerned with hyperglycemia, weight and body composition.

Mean SBP saw a reduction of 6.6 mm Hg in relacorilant patients compared to baseline. This is in contrast to a reduction of 2.1 mm Hg in placebo patients. The difference between these results was not statistically significant.

However, Corcept’s GRADIENT trial did meet some secondary endpoints and was well-tolerated. Patients taking relacorilant exhibited clinically meaningful and statistically significant improvements in hypertension, hyperglycemia, weight and body composition compared to baseline. In contrast, placebo patients did not.

Cushing’s syndrome is caused by an excess of cortisol and primarily affects those using steroid medications, which contain a synthetic version of the hormone. The condition is characterised by an increase of fat (particularly on the neck and shoulders), a change in face shape, stretch marks and skin which bruises easily. Cushing’s syndrome can also cause hypertension.

Corcept Therapeutics also shared that relacorilant was well-tolerated in the GRADIENT trial. It reported that there were no cases of relacorilant-induced hypokalemia, endometrial hypertrophy or related vaginal bleeding, adrenal insufficiency or QT prolongation.

The NDA submission for relacorilant for Cushing’s syndrome is expected this quarter. The GRADIENT trial will support results from the company’s GRACE trial, which were shared in June. The GRACE trial included 152 patients and met its primary endpoint of loss of hypertension control in the randomised-withdrawal phase.

Considering the results of the GRADIENT trial, Corcept Therapeutics’ chief development officer Bill Guyer said: “GRADIENT’s positive results in patients with Cushing’s syndrome confirm relacorilant’s promise as a significant medical advancement for the treatment of this deadly disease. As was true in the GRACE study, patients in GRADIENT who received relacorilant experienced clinically meaningful improvements in a broad range of hypercortisolism signs and symptoms, without suffering some of the serious adverse effects that can arise in patients taking currently approved treatments.

“These data will be a powerful addition to relacorilant’s NDA, which we plan to submit by year-end.”

https://www.clinicaltrialsarena.com/news/corcepts-relacorilant-gradient-trial-misses-primary-endpoint/?cf-view

Filed under: Clinical trials, Cushing's, Treatments | Tagged: , , | Leave a comment »