Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study

Maria Fleseriu, Stephan Petersenn, Beverly M.K. Biller, Pinar Kadioglu, Christophe De Block, Guy T'Sjoen, Marie Christine Vantyghem, Libuse Tauchmanova, Judi Wojna, Michael Roughton, André Lacroix, John Newell-Price

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1 Scopus citations

Abstract

Objectives: Many patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long-acting pasireotide during a long-term extension study in patients with CD. Design: Open-label extension to a 12-month Phase III study of long-acting pasireotide in CD (N = 150; NCT01374906). Patients: Patients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) or receiving clinical benefit at core study end could continue long-acting pasireotide during the extension. Results: Eighty-one of 150 (54.0%) enrolled patients entered the extension. Median overall exposure to pasireotide at study end was 23.9 months; 39/81 (48.1%) patients completed the extension (received ≥ 12 months’ treatment during the extension and could transit to a separate pasireotide safety study). mUFC was ≤ULN in 42/81 (51.9%), 13/81 (16.0%) and 43/81 (53.1%) patients at extension baseline, month (M) 36 and last assessment. Median mUFC remained within normal limits. Median late-night salivary cortisol was 2.6 × ULN at core baseline and 1.3 × ULN at M36. Clinical improvements were sustained over time. Forty-two (51.9%) patients discontinued during the extension: 25 (30.9%) before M24 and 17 (21.0%) after M24. Hyperglycaemia-related AEs occurred in 39.5% of patients. Mean fasting glucose (FPG) and glycated haemoglobin (HbA1c) were stable during the extension, with antidiabetic medication initiated/escalated in some patients. Sixty-six (81.5%) and 71 (88.9%) patients were classified as having diabetes (HbA1c ≥ 6.5%, FPG ≥ 7.0 mmol/L, antidiabetic medication use, or history of diabetes) at extension baseline and last assessment. Conclusions: Long-acting pasireotide provided sustained biochemical and clinical improvements, with no new safety signals emerging, supporting its use as an effective long-term therapy for CD.

Original languageEnglish (US)
Pages (from-to)776-785
Number of pages10
JournalClinical Endocrinology
Volume91
Issue number6
DOIs
StatePublished - Dec 1 2019

Keywords

  • Cushing syndrome
  • Cushing's disease
  • Phase III
  • extension
  • hypercortisolism
  • pasireotide
  • pituitary

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Fleseriu, M., Petersenn, S., Biller, B. M. K., Kadioglu, P., De Block, C., T'Sjoen, G., Vantyghem, M. C., Tauchmanova, L., Wojna, J., Roughton, M., Lacroix, A., & Newell-Price, J. (2019). Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study. Clinical Endocrinology, 91(6), 776-785. https://doi.org/10.1111/cen.14081