Full GRACE Results Shed Further Light on Effects of Relacorilant in Hypercortisolism

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At Heart in Diabetes, full results of the GRACE trial detailed the benefits of relacorilant use from both parts of the 2-part, phase 3 trial.

Rosario Pivonello, MD, PhD | Credit: University of Naples Frederico

Rosario Pivonello, MD, PhD
Credit: University of Naples Frederico

Final results of the GRACE trial presented at The Metabolic Institute of America’s 8th Heart in Diabetes meeting provide the greatest insight yet into the effects of relacorilant on blood pressure control among patients with hypercortisolism.1

Presented at the meeting by principal investigator Rosario Pivonello, MD, PhD, professor of Endocrinology at Università Federico II di Napoli, final results of the trial detail the effects of the selective cortisol modulator beyond the primary endpoint, including an analysis of the trial’s safety results.1

“The data from GRACE make a compelling case for the use of relacorilant in patients with endogenous hypercortisolism. That patients experienced clinically significant improvements in hypertension, hyperglycemia and the other signs and symptoms of Cushing’s syndrome, without significant safety burden, is greatly encouraging for physicians and the patients they seek to help,” said Pivonello, in Corcept Therapeutics’ announcement of primary endpoint results.2

GRACE was designed as a 2-part, phase 3 trial, with the first part being an open-label phase where 152 patients with Cushing’s syndrome and either hypertension, hyperglycemia, or both received relacorilant for 22 weeks.1

In this portion of the trial, 63% of patients with hypertension met the study’s response criteria, with use associated with rapid and sustained improvements for both systolic (mean reduction, 7.9 mmHg; P <.0001) and diastolic (mean reduction, 5.4 mmHg; P <.0001) at 22 weeks. Among those with hyperglycemia, all patients achieved clinically meaningful and statistically significant improvements in glucose metabolism, with 50% meeting the study’s response criteria.1

This part of the trial was followed by a double-blind, randomized, withdrawal period, which allowed investigators assess the trial’s primary outcome of interest—the maintenance of blood pressure control. In this portion of the trial, patients who met response criteria were randomized 1:1 to continue relacorilant or switch to placebo therapy for 12 weeks.1

According to data presented by Pivonello, results indicated loss of blood pressure control was 83% less likely to occur among patients relieving relacorilant compared to placebo (OR, 0.17; P = .02). Pivonello also highlighted similar blood pressure trends favoring use of relacorilant over placebo therapy were observed for 24-hour systolic and diastolic blood pressure, daytime systolic and diastolic blood pressure, and nighttime systolic and diastolic blood pressure.1

When discussing the effects on glycemic measurements, Pivonello noted patients who switched to placebo experienced significant increases in glucose area under the curve (AUC) and HbA1c, which was not observed among those receiving relacorilant. Among patients randomized to relacorilant, glycemic measures were maintained. Pivonello pointed out similar trends, with results favoring relacorilant, were witnessed when assessing effects on body composition, with those randomized to placebo experiencing a deterioration in body composition.1

When assessing safety, results suggested back pain (relacorilant vs placebo: 16.7% vs 18.8%), headache (10.0% vs 12.5%), arthralgia (10.0% vs 9.4%), insomnia (0% vs 12.5%), and pain in extremity (6.7% vs 6.3%) were the only adverse events occurring in 5% or more of patients in the trial.1

In addition to the final results presentation delivered by Pivonello, the meeting also featured a presentation led by Ralph DeFronzo, MD, chief of the Diabetes Division and professor of medicine at UT Health San Antonio, on how recent advances, including the GRACE trial, have contributed to a greater understanding of the relationship between hypertension, hyperglycemia, and hypercortisolism.3

References:

  1. Pivonello R, Arnaldi G, Auchus RJ. Medical Treatment of Hypercortisolism with Relacorilant: Final Results of the Phase 3 GRACE Study. Abstract presented at 8th Heart in Diabetes. Philadelphia, PA. June 07-09, 2024.
  2. Corcept Therapeutics, Incorporated. Corcept announces primary endpoint met in pivotal phase 3 GRACE trial of relacorilant in patients with hypercortisolism (Cushing’s syndrome). Corcept Therapeutics, Incorporated. May 28, 2024. Accessed June 8, 2024. https://ir.corcept.com/news-releases/news-release-details/corcept-announces-primary-endpoint-met-pivotal-phase-3-grace.
  3. DeFronzo R. HYPERTENSION AND HYPERGLYCEMIA: TWIN SISTERS MASQUERADING AS CUSHING SYNDROME. Abstract presented at 8th Heart in Diabetes. Philadelphia, PA. June 07-09, 2024.
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