Levoketoconazole: a novel treatment for endogenous Cushing's syndrome

Maria Fleseriu, Richard J. Auchus, Rosario Pivonello, Roberto Salvatori, Sabina Zacharieva, Beverly M.K. Biller

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Introduction: Endogenous Cushing’s syndrome (CS) is a rare, life-threatening endocrine disorder that is caused by chronic exposure to cortisol overproduction. Levoketoconazole (Recorlev), a 2S, 4R stereoisomer of ketoconazole, is a steroidogenesis inhibitor under investigation for the treatment of CS. Areas covered: This review covers the pharmacology, efficacy, and safety of levoketoconazole for the treatment of patients with endogenous CS. Expert opinion: Based on the preclinical and clinical pharmacology findings, levoketoconazole appears to be the relevant enantiomer of ketoconazole for inhibition of steroidogenesis, with more potent inhibition of both cortisol and androgen synthesis relative to ketoconazole racemate and the 2R, 4S stereoisomer dextroketoconazole. Results from the phase III SONICS study showed that levoketoconazole was effective in normalizing cortisol levels and improving biomarkers of cardiovascular risk in a significant percentage of patients. In addition, treatment with levoketoconazole showed improvements in subjective clinical assessments of clinician-rated CS clinical signs and symptoms, patient-reported quality of life, and depression symptom severity. Testosterone levels decreased significantly in women. Levoketoconazole had an acceptable safety profile with no unexpected safety signals. The favorable pharmacology, efficacy, and safety profile of levoketoconazole supports its use as medical therapy for CS, if approved.

Original languageEnglish (US)
Pages (from-to)159-174
Number of pages16
JournalExpert Review of Endocrinology and Metabolism
Volume16
Issue number4
DOIs
StatePublished - 2021

Keywords

  • Cushing’s disease
  • Cushing’s syndrome
  • cortisol
  • ketoconazole
  • levoketoconazole
  • medical therapy
  • steroidogenesis inhibitor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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