ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 26 P265

Pasireotide (SOM230) demonstrates efficacy in patients with Cushing's disease: results from a large, randomized-dose, double-blind, Phase III study

A Colao1, S Petersenn2, J Newell-Price3, J W Findling4, F Gu5, M Maldonado6, U Schoenherr6, D Mills6, L R Salgado7 & B M K Biller8

1Section of Endocrinology, Department of Molecular and Clinical Endocrinology and Oncology, University of Naples Federico II, Naples, Italy; 2ENDOC Center for Endocrine Tumors, Hamburg, Germany; 3The Medical School, University of Sheffield, Sheffield, UK; 4Division of Endocrinology, Metabolism, and Clinical Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; 5Peking Union Medical College Hospital, Beijing, People’s Republic of China; 6Clinical Development, Oncology Business Unit, Novartis Pharma AG, Basel, Switzerland; 7Division of General Internal Medicine, Hospital das Clínicas, University of São Paulo School, São Paulo, Brazil; 8Neuroendocrine Clinical Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

Introduction: Pasireotide is a multi-receptor targeted somatostatin analogue with high affinity for sst5, which is commonly expressed in corticotroph adenomas, thus having potential as therapy for Cushing’s disease.

Methods: One hundred and sixty-two patients with persistent/recurrent or de novo (if not surgical candidates) Cushing’s disease were randomized (double-blind) to pasireotide 600 μg (n=82) or 900 μg (n=80) sc bid. After 3mo, patients with UFC>2×ULN (ULN: 145 nmol/24 h) or UFC>baseline were unblinded and the dose increased by 300 μg bid. All others continued on the same double-blind dose to 6mo. Months 6–12 were open-label with dose titration performed when needed. Primary endpoint: UFC≤ULN at 6mo without dose up-titration from the randomized dose.

Results: The median percent decrease in UFC from baseline to month 2 was ~50% in both treatment arms and remained stable throughout the study. At 6mo, 14.6% (600 μg) and 26.3% (900 μg) of patients met the primary endpoint; at 12mo, 13.4% (600 μg) and 25.0% (900 μg) of patients had UFC≤ULN. Patients with baseline UFC≤5×ULN were more likely to achieve normalized UFC. Most uncontrolled patients could be identified within 2mo, based on UFC. Serum and salivary cortisol and plasma ACTH were also reduced. As mean UFC decreased, clinical signs and symptoms, and QoL improved. The safety profile of pasireotide was similar to that of other somatostatin analogues (mostly transient GI discomfort), except for hyperglycemia; 70% of patients had a hyperglycemia-related AE. Elevated fasting blood glucose and HbA1c were seen soon after pasireotide initiation. Patients without diabetes at baseline had a lower degree of hyperglycemia. Thirteen (8.0%) patients had an AE of hypocortisolism, responsive to dose reduction.

Conclusion: Results from this Phase III study show that pasireotide significantly reduces elevated cortisol levels and provides clinical benefit in patients with Cushing’s disease, supporting its potential for use as the first specific pituitary-targeted treatment in this disorder.

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