Long-term efficacy and safety of subcutaneous pasireotide in acromegaly: results from an open-ended, multicenter, Phase II extension study

Stephan Petersenn, Andrew J Farrall, Christophe De Block, Shlomo Melmed, Jochen Schopohl, Philippe Caron, Ross Cuneo, David Kleinberg, Annamaria Colao, Matthieu Ruffin, Karina Hermosillo Reséndiz, Gareth Hughes, Ke Hu, Ariel Barkan, Stephan Petersenn, Andrew J Farrall, Christophe De Block, Shlomo Melmed, Jochen Schopohl, Philippe Caron, Ross Cuneo, David Kleinberg, Annamaria Colao, Matthieu Ruffin, Karina Hermosillo Reséndiz, Gareth Hughes, Ke Hu, Ariel Barkan

Abstract

Pasireotide has a broader somatostatin receptor binding profile than other somatostatin analogues. A 16-week, Phase II trial showed that pasireotide may be an effective treatment for acromegaly. An extension to this trial assessed the long-term efficacy and safety of pasireotide. This study was an open-label, single-arm, open-ended extension study (primary efficacy and safety evaluated at month 6). Patients could enter the extension if they achieved biochemical control (GH ≤ 2.5 μg/L and normal IGF-1) or showed clinically relevant improvements during the core study. Thirty of the 60 patients who received pasireotide (200-900 μg bid) in the core study entered the extension. At extension month 6, of the 26 evaluable patients, six were biochemically controlled, of whom five had achieved control during the core study. Normal IGF-1 was achieved by 13/26 patients and GH ≤ 2.5 μg/L by 12/26 at month 6. Nine patients received pasireotide for ≥24 months in the extension; three who were biochemically controlled at month 24 had achieved control during the core study. Of 29 patients with MRI data, nine had significant (≥20%) tumor volume reduction during the core study; an additional eight had significant reduction during the extension. The most common adverse events were transient gastrointestinal disturbances; hyperglycemia-related events occurred in 14 patients. Twenty patients had fasting plasma glucose shifted to a higher category during the extension. However, last available glucose measurements were normal for 17 patients. Pasireotide has the potential to be an effective, long-term medical treatment for acromegaly, providing sustained biochemical control and significant reductions in tumor volume.

Figures

Fig. 1
Fig. 1
Percentage change in pituitary tumor volume from core study baseline to the last extension study visit (n = 29). The GH and IGF-1 responders shown here are those who were responders at any time point
Fig. 2
Fig. 2
Coronal T1 MR images of a patient, illustrating significant tumor volume reduction during treatment with pasireotide
Fig. 3
Fig. 3
Summary of acromegaly symptom severity at extension baseline and end of the extension study

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