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

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