Results From Grace, a Phase 3 Double-blind, Randomized-withdrawal Study of the Selective Glucocorticoid Receptor Modulator Relacorilant for the Treatment of Endogenous Hypercortisolism (Cushing Syndrome)

Summary & Conclusions

Relacorilant, a selective glucocorticoid receptor (GR) modulator, was designed to decrease excess cortisol activity at the GR and improve the clinical signs and symptoms of endogenous Cushing syndrome (CS)
GRACE was the largest prospective, interventional phase 3 study to date in patients with CS of all etiologies and uncontrolled hypertension and/or hyperglycemia
Significant improvements in hypertension, hyperglycemia, and other manifestations of cortisol excess were observed in the open-label phase, along with a favorable safety profile
GRACE met its primary endpoint of loss of hypertension control in the randomized-withdrawal phase (odds ratio 0.17 for relacorilant vs placebo; P=0.02)
Due to relacorilant’s unique mechanism of action in the corticotroph cells of the pituitary gland, the observed efficacy was seen without increases in cortisol concentrations and associated hypokalemia
- No cases of drug-induced irregular vaginal bleeding associated with endometrial hyperplasia
- No cases of independently confirmed QT prolongation
- No adrenal insufficiency
Consistent with its known safety profile, relacorilant was well-tolerated in both phases of GRACE
- Adverse events were mostly mild-to-moderate in severity, and consistent with glucocorticoid withdrawal, which may occur with any treatment for CS
- No differences in adverse events were observed in the randomized-withdrawal phase between relacorilant and placebo