Abstract
Disclosure: G.A. Dobri: Camurus, Recordati Rare Diseases, Xeris. G. Arnaldi: Recordati Rare Diseases and HRA Pharma. R.J. Auchus: Neurocrine Biosciences/Neurocrine UK, LTD, Spruce Biosciences, Corcept Therapeutics Incorporated, Crinetics Pharmaceuticals, Recordati Rare Diseases, Adrenas Therapeutics, Mineralys Therapeutics, Quest Diagnostics, Xeris Pharmaceuticals, Novo Nordisk, H Lundbeck A/S, Sparrow Pharmaceuticals, Astellas Pharmaceuticals, Acerand Therapeutics, OMass Therapeutics, Blue Earth Diagnostics, LTD, Aspect Biosystems. C. Badiu: Corcept Therapeutics Incorporated, Novo Nordisk, Lundbeck, Pfizer, Ipsen, Merck. P.K. Fazeli: Crinetics, Xeris, Amryt, Camurus, Regeneron, Quest Diagnostics, Corcept Therapeutics Incorporated. R.A. Feelders: Corcept Therapeutics Incorporated, Recordati Rare Diseases. Z.C. Hannoush: None. A. Kautzky-Willer: None. H.J. Miller: None. D.A. Niculescu: None. R. Pivonello: Recordati AG, Corcept Therapeutics Incorporated, Strongbridge Biopharma, Neurocrine Biosciences, Crinetics Pharmaceuticals, H. Lundbeck A/S. A. Ranetti: None. M. Recasens: None. M. Reincke: Recordati Rare Diseases, Ipsen, Crinetics, HRA Pharma, Lundbeck. J. Silverstein: Xeris Biopharma, Chiesi USA, AbbVie Inc, Bayer, Camurus, DebioPharm, Fractyl Health, Inc., Sparrow Pharmaceuticals. A. Stigliano: HRA Pharma, Recordati Rare Diseases. A.L. Hand: Corcept Therapeutics Incorporated. A. Kesner-Hays: Corcept Therapeutics Incorporated. K.A. Araque: Corcept Therapeutics Incorporated. A. Moraitis: Corcept Therapeutics Incorporated. Relacorilant is an investigational, oral, selective glucocorticoid receptor (GR) modulator in development for the treatment of any type of endogenous hypercortisolism (HC). Previous case reports suggested that the pituitary tumor effects of relacorilant in patients with Cushing Disease (CD) are distinct from those of the FDA-approved GR antagonist mifepristone (Pivonello Front Endocrinol 2022). Relacorilant appears to upregulate previously suppressed somatostatin receptor type 2 expression, resulting in tumor-specific antisecretory and antiproliferative effects, including tumor shrinkage. Here, we present data on the effect of relacorilant on pituitary tumors based on magnetic resonance imaging (MRI) in patients with CD participating in the GRACE study (NCT03697109). GRACE was a phase 3 study with 2 parts: 1) a 22-week open-label phase in which adults (N=152) with HC and hypertension, hyperglycemia, or both received relacorilant 100 mg to 400 mg once daily based on tolerability and efficacy, and 2) a double-blind, placebo-controlled randomized withdrawal phase in which participants completing the open-label phase and meeting the prespecified response criteria were randomized 1:1 to continue to receive relacorilant or be switched to placebo for 12 weeks. Pituitary MRIs were taken at baseline and at the end of the open-label phase. Tumor volume (mm3) change was defined as a 20% increase or decrease from baseline. In GRACE, 54 patients had CD and evaluable pituitary MRIs at baseline and postbaseline. At baseline, 22 (40.7%) had nonvisible tumors, 24 (44.4%) had microadenomas, and 8 (14.8%) had macroadenomas. Postbaseline, all nonvisible tumors remained unchanged, 20 (83.3%) microadenomas decreased in volume or remained unchanged, and 5 (62.5%) macroadenomas decreased in volume or remained unchanged. Relacorilant was well-tolerated and effective at improving hypertension and hyperglycemia parameters in this study. In summary, pituitary tumor volume decreased or remained unchanged following treatment with relacorilant for the majority of patients with CD in the GRACE study. Relacorilant was also well-tolerated and led to significant improvements in HC-related signs and symptoms. Presentation: Monday, July 14, 2025