Pasireotide in Acromegaly: An Overview of Current Mechanistic and Clinical Data.

BACKGROUND: Acromegaly is an insidious neuroendocrine disorder caused by hypersecretion of growth hormone (GH) by a somatotroph adenoma. Somatostatin receptor ligands (SRLs) are recommended as first-line medical therapy in patients for whom surgery has failed or is contraindicated. There are 5 known somatostatin receptor subtypes (SSTRs), 2 of which, i.e. SSTR2 and SSTR5, are expressed by a majority of somatotroph adenomas. The currently available SRLs, i.e. octreotide and lanreotide, primarily bind to SSTR2. Pasireotide (SOM230) is a new multireceptor-targeted SRL which has a broader binding profile and an increased affinity for SSTR1, 2, 3, and 5.

METHODS: PubMed searches were performed to identify all of the available published English language data on pasireotide with regard to the mechanism of action, in vitro effects, and clinical data.

RESULTS: Preclinical studies have demonstrated that pasireotide has a broader range of functional activity than octreotide. Recently, the efficacy of pasireotide in attenuating GH and insulin-like growth factor 1 (IGF-1) levels in patients with acromegaly has been evaluated in phase III clinical trials. Pasireotide demonstrated superiority over octreotide in achieving biochemical control (i.e. GH ≤2.5 µg/l and age- and sex-matched IGF-1 normalization) in patients with acromegaly, as well as significant efficacy in treating patients who were previously inadequately controlled on the maximum allowed doses of octreotide and lanreotide. Pasireotide-induced hyperglycemia was the most concerning adverse event but was reversible upon discontinuation of pasireotide.

CONCLUSION: The clinical data support pasireotide as a promising new therapy for the treatment of acromegaly, and the long-acting formulation was recently approved in the US and Europe for the treatment of acromegaly.