SUN-463 Efficacy and Safety of Relacorilant in Individuals With Adrenal Hypercortisolism: Results From the Phase 3 GRACE and GRADIENT Studies

Abstract Disclosure: U. Dischinger: Recordati, Novo Nordisk, Alnylam, Merck. A. Al-Karadsheh: None. C. Badiu: Corcept Therapeutics, Lundbeck, Novo Nordisk, Ipsen, Merck, Pfizer, Inc. F. Ceccato: Novartis Pharmaceuticals, HRA Pharmaceuticals, Novo Nordisk, Recordati. H. East: Corcept Therapeutics, Amgen Inc, Boehringer Ingelheim, Lilly USA, LLC. A. Gilis-Januszewska: Recordati, Novo Nordisk, Ipsen, Pfizer, Inc. O. Hamidi: Corcept Therapeutics, Lantheus, Recordati Rare Diseases, Neurocrine Biosciences, Crinetics Pharmaceuticals, Camurus. A.H. Hamrahian: Corcept Therapeutics, Spruce Biosciences, AstraZeneca, Cristcot. Z.C. Hannoush: None. A. Kautzky-Willer: None. M.Á. Mangas-Cruz: None. D.A. Niculescu: None. J.C. Parker: Corcept Therapeutics, Novo Nordisk, Insulet Corporation. R. Pivonello: Corcept Therapeutics, Crinetics, Lundbeck, Recordati;, Neurocrine, Strongbridge, HRA Pharmaceuticals. A. Ranetti: None. S. Rovner: Amgen Inc, Bayer, Inc., Corcept Therapeutics, Eli Lilly & Company, Novo Nordisk. G. Shlomai: None. A. Stigliano: None. M. Terzolo: HRA Pharmaceuticals, Corcept Therapeutics. F.J. Tinahones Madueño: None. A. Kesner-Hays: Corcept Therapeutics. A.L. Hand: Corcept Therapeutics. K.A. Araque: Corcept Therapeutics. A.G. Moraitis: Corcept Therapeutics. In the phase 3 GRACE study, the selective glucocorticoid receptor (GR) modulator relacorilant significantly improved blood pressure control and showed improvements in signs and symptoms of endogenous hypercortisolism of all etiologies. The phase 3 GRADIENT study investigated relacorilant in individuals with adrenal hypercortisolism. Here, we present results from a pooled analysis that assessed relacorilant efficacy and safety in those individuals with adrenal hypercortisolism and similar baseline characteristics from both studies. GRACE (NCT03697109) comprised a 22-week, open-label treatment phase of relacorilant 100-400 mg followed by a 12-week, double-blind, placebo (PBO)-controlled randomized withdrawal phase. GRADIENT (NCT04308590) was a 22-week, randomized, double-blind, PBO-controlled study of relacorilant 100-400 mg daily. Both studies enrolled adults with endogenous hypercortisolism and hypertension (HTN) and/or hyperglycemia. The current analysis included the GRACE subgroup with adrenal hypercortisolism (n=34) and the GRADIENT subgroup with similar baseline and biochemical characteristics (relacorilant, n=26; PBO, n=27). Relacorilant data from the 22-week periods in both studies were pooled and compared with GRADIENT PBO data. Results are reported as least squares mean change from baseline to week 22. In individuals with HTN (n=56), relacorilant significantly decreased systolic and diastolic blood pressure measured by 24-hour ambulatory blood pressure measurement (-10.1 and -6.3 mm Hg, respectively) vs PBO (+1.5 and +2.2 mm Hg, respectively; both P<0.01). In individuals with hyperglycemia (n=64), relacorilant significantly improved fasting glucose and glucose area under the curve (-0.7 mmol/L and -2.4 mmol/L*hr, respectively) vs PBO (+0.4 mmol/L and +1.3 mmol/L*hr, respectively; both P<0.05). Study participants also experienced weight loss with relacorilant (-4.1 kg) vs PBO (-1.0 kg; P<0.01). Adverse events were generally mild to moderate; no new safety signals were identified. The safety profile in these studies was consistent with relacorilant’s GR specificity and mechanism of action. There were no cases of adrenal insufficiency or vaginal bleeding associated with endometrial hypertrophy, and no cases of drug-induced hypokalemia or QT interval prolongation. In summary, relacorilant was well-tolerated and resulted in clinically and statistically significant treatment benefits in participants with adrenal hypercortisolism in the phase 3 GRACE and GRADIENT studies. Presentation: Sunday, July 13, 2025