Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study.

Introduction/purpose: Relacorilant is a selective glucocorticoid receptor modulator (SGRM) with no progesterone receptor activity. We evaluated the efficacy and safety of relacorilant in patients with endogenous Cushing syndrome (CS).
Materials and Methods: A single-arm, open-label, phase 2, dose-finding study with 2 dose groups (NCT02804750, https://clinicaltrials.gov/ct2/show/NCT02804750) was conducted at 19 sites in the U.S. and Europe. Low-dose relacorilant (100-200 mg/d; n = 17) was administered for 12 weeks or high-dose relacorilant (250-400 mg/d; n = 18) for 16 weeks; doses were up-titrated by 50 mg every 4 weeks. Outcome measures included proportion of patients with clinically meaningful changes in hypertension and/or hyperglycemia from baseline to last observed visit. For patients with hypertension, clinical response was defined as a ≥5-mmHg decrease in mean systolic or diastolic blood pressure, measured by a standardized and validated 24-h ABPM. For patients with hyperglycemia, clinical response was defined ad-hoc as ≥0.5% decrease in HbA1c, normalization or ≥50-mg/dL decrease in 2-h plasma glucose value on oral glucose tolerance test, or decrease in daily insulin (≥25%) or sulfonylurea dose (≥50%).
Results: 35 adults with CS and hypertension and/or hyperglycemia (impaired glucose tolerance or type 2 diabetes mellitus) were enrolled, of which 34 (24 women/10 men) received treatment and had postbaseline data. In the low-dose group, 5/12 patients (41.7%) with hypertension and 2/13 patients (15.4%) with hyperglycemia achieved response. In the high-dose group, 7/11 patients (63.6%) with hypertension and 6/12 patients (50%) with hyperglycemia achieved response. Common (≥20%) adverse events included back pain, headache, peripheral edema, nausea, pain at extremities, diarrhea, and dizziness. No drug-induced vaginal bleeding or hypokalemia occurred.
Conclusions: The SGRM relacorilant provided clinical benefit to patients with CS without undesirable antiprogesterone effects or drug-induced hypokalemia.
Competing Interests: The authors declare that this study received funding from Corcept Therapeutics (Menlo Park, CA, USA). The funder had a role in study design, data collection and analysis, and AM, as an author of the manuscript and employee of Corcept Therapeutics, had a role in the study design, the decision to publish, the interpretation of clinical data, the revision of the manuscript, and approval of the final manuscript to submit. Open Access publication fees were paid by Corcept Therapeutics. RP: Consultant: Ferring, Ipsen, Novartis, Pfizer, ViroPharma-Shire; Speaker: Novartis, ViroPharma-Shire; Research support: Corcept Therapeutics, Novartis, ViroPharma-Shire; Grant support: IBSA, Novartis, Pfizer, ViroPharma-Shire. IB: Consultant: HRA Pharma, Sparrow Pharmaceutics, Strongbridge; Data and Safety Monitoring Panel, Adrenas. RF: Consultant: Corcept Therapeutics; Speaker: HRA Pharma. AK: Consultant: Strongbridge; Research support: Corcept Therapeutics. MG: Research support: Corcept Therapeutics, Crinetics, Ionis, Ipsen, Novartis, Novo Nordisk, Opko, Strongbridge, Teva. CM: Consultant: Horizon Therapeutics; Research support: Corcept Therapeutics, Eli Lilly, Medtronic. MT: Consultant: HRA Pharma; Research support: Corcept Therapeutics. NE: Consultant: Corcept Therapeutics, Pentara, Trialwise. AM: Employee: Corcept Therapeutics. The remaining author (JK) declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AALC declared a shared affiliation with one of the authors, RP, to the handling editor at time of review. Author NE was employed by company Trialwise.
(Copyright © 2021 Pivonello, Bancos, Feelders, Kargi, Kerr, Gordon, Mariash, Terzolo, Ellison and Moraitis.)