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


Clin Endocrinol. 2019;91(6):776-785. 

In This Article

Abstract and Introduction


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.


Cushing's disease (CD) is a rare endocrine disorder characterized by overproduction of cortisol by the adrenal glands, secondary to an adrenocorticotropic hormone (ACTH)–secreting pituitary adenoma (corticotropinoma).[1] CD is associated with significant multisystem morbidity, impaired quality of life (QoL) and increased mortality if inadequately treated.[2,3]

Selective resection of the corticotropinoma by transsphenoidal surgery is the first-choice treatment for CD, but surgical success rates vary and depend on the expertise of the surgeon. CD persists in 10%-35% of patients after surgery,[4,5] while recurrence rates range from 15% to 66% after a variable duration of remission.[6–8] Medical therapy plays a prominent role in the management of persistent or recurrent CD, as well as in patients who are not candidates for surgery, such as those considered to be at high surgical risk and/or with acute complications of CD.[2,8–10]

Given the chronic nature of CD, many patients require long-term pharmacotherapy to achieve and maintain the goals of treatment: to control cortisol excess, reverse clinical features and complications of hypercortisolism, improve QoL, control tumour mass and increase life expectancy.[8] A comprehensive understanding of the long-term efficacy and safety of available medical treatment options is therefore central to achieving optimal outcomes for patients.

Based on the results of a 12-month Phase III study,[11] a long-acting intramuscular formulation of pasireotide suitable for monthly administration has been approved in the EU, United States and other countries worldwide for the treatment of CD.[12,13] Here, we report the efficacy and safety of long-acting pasireotide during a long-term extension (median treatment duration: 23.9 months) to the Phase III study.