Endocrine Abstracts (2013) 32 P845 | DOI: 10.1530/endoabs.32.P845

Pasireotide LAR and octreotide LAR maintain inhibition of GH and IGF1 in patients with acromegaly: 12-month extension phase of a randomized, double-blind, multicenter, phase III study

Michael Sheppard1, Marcello Bronstein2, Pamela Freda3, Omar Serri4, Laura De Marinis5, Luciana Naves6, Liudmila Rozhinskaya7, Karina Hermosillo Reséndiz8, Matthieu Ruffin9, Kobby Asubonteng8 & Annamaria Colao10


1University of Birmingham, Edgbaston, Birmingham, UK; 2University of São Paulo Medical School, São Paulo, Brazil; 3Columbia University College of Physicians and Surgeons, New York, New York, USA; 4University of Montreal, Montreal, Canada; 5Università Cattolica del Sacro Cuore, Rome, Italy; 6University of Brasília, Brasília, Brazil; 7National Research Center for Endocrinology of the Russian Academy of Medical Science, Moscow, Russia; 8Novartis Pharmaceuticals Corporation, Florham Park, New Jersey, USA; 9Novartis Pharma AG, Basel, Switzerland; 10Università Federico II di Napoli, Naples, Italy.


Introduction: Pasireotide LAR was significantly superior to octreotide LAR at providing biochemical control in a 12-month trial in 358 medically naïve patients with acromegaly. Patients with clinical benefit or GH <2.5 μg/l and IGF1≤ULN could continue therapy in the extension study.

Methods: Patients entering the extension (pasireotide LAR, n=74; octreotide LAR, n=46) were followed up to month 26 (core plus extension) for octreotide LAR, whereas pasireotide LAR patients could continue beyond month 26. Dose titration to pasireotide LAR 60 mg/28 days or octreotide LAR 30 mg/28 days (if GH ≥2.5 μg/l and/or IGF1>ULN) or to pasireotide LAR 20 mg/28 days or octreotide LAR 10 mg/28 days (for tolerability) was permitted throughout core and extension.

Results: Mean duration of exposure was 465 days (pasireotide LAR) and 412 days (octreotide LAR). 51 pasireotide LAR and 36 octreotide LAR patients completed month 26. Suppression of GH and IGF1 was maintained throughout the extension in both arms. Median GH (μg/l) and IGF1 (×ULN) in pasireotide LAR vs octreotide LAR patients were: at baseline, 8.8 vs 10.1 and 2.9 vs 2.9; at month 12, 1.9 vs 2.0 and 0.9 vs 1.3; and at month 25, 1.0 vs 1.0 and 0.6 vs 0.9. Median percentage change in GH and IGF1 at month 25 was −83% and −71% with pasireotide LAR and −86% and −64% with octreotide LAR. Mean percentage change in tumor volume from core baseline to month 25 was −51.8% (n=54) for pasireotide LAR and −55.0% (n=34) for octreotide LAR. Both treatments improved acromegaly symptom scores. Most common AEs during the core and extension in both treatment arms were diarrhea, cholelithiasis, hyperglycemia, headache, and diabetes mellitus. Hyperglycemia-related AEs were more frequent with pasireotide LAR than octreotide LAR (62.9% (n=112/178) vs 25.0% (n=45/180)).

Conclusions: These results suggest that pasireotide LAR and octreotide LAR provide long-term inhibition of GH and IGF1 in patients with acromegaly.