KORLYM MECHANISM OF ACTION

Korlym modulates cortisol activity to preserve important physiological effects of cortisol while reducing certain negative effects of excess cortisol1,2

Korlym is a reversible glucocorticoid receptor (GR) antagonist that1:

  • Competes with cortisol at the GR site in a dose-dependent manner3

  • Preserves the important physiological effects of cortisol while reducing certain negative effects of excess cortisol2

Korlym improves hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing syndrome by modulating cortisol activity, which is a different mechanism of action compared with2,4-7:

  • Other medications for endogenous hypercortisolism

  • Medications for type 2 diabetes

Korlym competes with cortisol at the GR site3

See how excess cortisol may cause hyperglycemia and how Korlym competes with cortisol at the GR site.

  • Measurement of cortisol is not an effective measure of treatment response with Korlym4

    • Korlym does not lower cortisol levels but rather modulates the activity of cortisol at the receptor, thereby reducing both signs and symptoms of hypercortisolism2

  • Korlym is not indicated for the treatment of type 2 diabetes mellitus unrelated to hypercortisolism due to endogenous Cushing syndrome4

Glucocorticoid receptors in a cellular environment, with one receptor highlighted and labeled 'Glucocorticoid Receptor' against a gradient blue-gray background.

Cortisol works by binding to and activating GRs, which are present in most body tissues.4,8,9

Cortisol molecule highlighted and labeled in a cellular environment against a gradient blue-gray background.

When cortisol activity is elevated, over time, there can be wide-ranging negative effects on the body, including impaired glucose tolerance, hypertension, osteoporosis, obesity, and cognitive issues.4,8,9

Molecular structure labeled 'KORLYM' in a cellular environment against a gradient blue-gray background.

Korlym competes with the binding of cortisol to the GR in a dose-dependent manner. With Korlym modulating cortisol activity at the GR, symptoms of hypercortisolism, such as high blood glucose, obesity, and cognitive issues, improve over time.4,8,9*

Because of the variability in clinical presentation and variability of response in the open label SEISMIC trial, it is uncertain whether improvements in body weight and psychiatric symptoms could be ascribed to the effects of Korlym.

Next: Learn more about Korlym efficacy and safety

References:
  1. Bourgeois S, Pfahl M, Baulieu EE. DNA binding properties of glucocorticosteroid receptors bound to the steroid antagonist RU-486. EMBO J. 1984;3(4):751-755. doi:10.1002/j.1460-2075.1984.tb01879
  2. Katznelson L, Loriaux DL, Feldman D, Braunstein GD, Schteingart DE, Gross C. Global clinical response in Cushing's syndrome patients treated with mifepristone. Clin Endocrinol (Oxf). 2014;80(4):562-569. doi:10.1111/cen.12332
  3. Sitruk-Ware R, Spitz IM. Pharmacological properties of mifepristone: toxicology and safety in animal and human studies. Contraception. 2003;68(6):409-420. doi:10.1016/s0010-7824(03)00171-9
  4. Korlym Prescribing Information. Corcept Therapeutics Incorporated.
  5. Recorlev [prescribing information]. Chicago, IL: Xeris Pharmaceuticals Incorporated.
  6. Isturisa [prescribing information]. Lebanon, NJ: Recordati Rare Disease Incorporated.
  7. Signifor LAR [prescribing information]. Lebanon, NJ: Recordati Rare Disease Incorporated.
  8. Raff H, Sharma ST, Nieman LK. Compr Physiol. 2014;4(2):739-769. doi:10.1002/cphy.c130035
  9. Di Dalmazi G, Vicennati V, Garelli S, et al. Lancet Diabetes Endocrinol. 2014;2(5):396-405. doi:10.1016/S2213-8587(13)70211-0