Improvements in the Clinical Signs and Symptoms of Cushing's Disease Following 12 Months' Treatment with Pasireotide are Not Restricted to Patients Who Achieve UFC Control

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 88-111-Cushing's Disease & Non-Functioning Hypothalamus-Pituitary Tumors
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-90
Rosario Pivonello*1, Stephan Petersenn2, Feng Gu3, Andrew Trovato4, Gareth Hughes5, Monica Ligueros-Saylan6, Luiz R Salgado7, André Lacroix8, Jochen Schopohl9 and Beverly MK Biller10
1Università Federico II di Napoli, Naples, Italy, 2ENDOC Center for Endocrine Tumors, Hamburg, Germany, 3Peking Union Medical College Hospital, Beijing, China, 4Novartis Pharma AG, Basel, Switzerland, 5Novartis Pharmaceuticals Corporation, Florham Park, NJ, 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, 7University of São Paulo Medical School, São Paulo, Brazil, 8Centre hospitalier de l’Université de Montréal, Montréal, QC, Canada, 9University of Munich, Munich, Germany, 10Massachusetts General Hospital, Boston, MA
Introduction: Pasireotide (Signifor®) reduced and normalized UFC in patients with Cushing’s disease in a large, randomized Phase III study. This analysis evaluates the effects of pasireotide on the signs and symptoms of Cushing’s disease according to the degree of UFC control.

Methods: Adult patients (n=162) with persistent/recurrent or de novo Cushing’s disease were randomized to pasireotide 600/900 μg sc bid. Dose titration (max: 1200 μg bid) was allowed after month 3: initiation or changes in antihypertensive, antidiabetic and lipid-lowering medications were permitted throughout the study. Changes in the symptoms of Cushing’s disease during pasireotide treatment were evaluated at 6 and 12 months. UFC measurements were conducted at central laboratories. Controlled (C) UFC was defined as UFC≤ULN at month 6, partially controlled (PC) as UFC>ULN but with ≥50% reduction from baseline at month 6, and uncontrolled (UC) as UFC>ULN without a ≥50% reduction from baseline at month 6. All data shown are mean [95% CI] values.

Results: At month 12, an overall decrease in UFC from baseline was observed in patients who were C (–68% [–79, –56]), PC (–64% [–80,–47]) and UC (–20% [–49, 9]) at month 6. Patients with UFC control at month 6 had the greatest change from baseline in systolic (–12 [–18,–6], –4 [–12, 4] and –3 [–8, 3] mmHg in C, PC and UC groups, respectively) and diastolic BP (–7 [–11, –3], –3 [–9, 2], –1 [–5, 3] in C, PC and UC groups, respectively) at 12 months. Improvements in BMI and weight at month 12 were observed in the three UFC response groups; C (–3 [–4, –2] kg/m2 and –8 [–10, –6] kg, respectively), PC (–2 [3, –1] kg/m2 and –4 [–7, –2] kg, respectively) and UC groups (–3 [–3, –2] kg/m2 and –7 [–9, –5] kg, respectively). Similar results were seen for facial rubor and striae. Fasting plasma glucose and HbA1clevels increased from baseline in all patients receiving pasireotide, irrespective of UFC control. The relative impact of concomitant medications on signs and symptoms could not be evaluated.

Conclusions: Treatment with pasireotide was accompanied by improvements in the signs and symptoms of Cushing’s disease, which were maintained for 12 months. While the treatment goal is biochemical control, it is notable that clinical improvements were not restricted to patients who achieved UFC control, suggesting improvements in UFC with pasireotide may be beneficial in improving signs and symptoms in patients with Cushing’s disease.

Disclosure: RP: Advisory Group Member, Novartis Pharmaceuticals, Speaker, Novartis Pharmaceuticals, Investigator, Novartis Pharmaceuticals, Advisory Group Member, Ipsen, Speaker, Ipsen, Investigator, Ibsa, Investigator, Pro Strakan, Investigator, Viropharma, Medical Advisory Board Member, Viropharma, Consultant, Italfarmaco, Investigator, Pfizer, Inc., Medical Advisory Board Member, Pfizer, Inc.. SP: Speaker, Pfizer, Inc., Medical Advisory Board Member, Ipsen, Speaker, Ipsen, Medical Advisory Board Member, Novartis Pharmaceuticals, Speaker, Novartis Pharmaceuticals, Medical Advisory Board Member, Pfizer, Inc.. AT: Employee, Novartis Pharmaceuticals. GH: Employee, Novartis Pharmaceuticals. ML: Employee, Novartis Pharmaceuticals. AL: Editor, Wolters Kluwer, Speaker, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Investigator, Novartis Pharmaceuticals. JS: Consultant, Novartis Pharmaceuticals, Consultant, Pfizer, Inc., Consultant, Ipsen. BMB: Consultant, HRA Pharma, Investigator, Corcept, Consultant, Novartis Pharmaceuticals, Investigator, Novartis Pharmaceuticals. Nothing to Disclose: FG, LRS

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Sources of Research Support: Novartis funded editorial support provided by Mudskipper