Comment
Acromegaly has attracted substantial interest among scientists and pharmaceutical researchers in the past few decades, leading to the development and licensing of several efficacious drugs in many countries, including octreotide and its long-acting formulation, lanreotide depot, and pegvisomant.1 Additionally, dopamine agonists, particularly cabergoline, also show useful activity in a subset of patients with acromegaly and have been used off label.1 The availability of a growing number of medical therapies for acromegaly is good news for both patients and their physicians. Although transsphenoidal pituitary surgery is becoming increasingly sophisticated with the availability of neuronavigation, endoscopes, and intraoperative MRI, a substantial proportion of patients do not achieve disease remission, particularly those with macroadenomas or locally invasive pituitary tumours.2 Furthermore, radiotherapy leads to disease remission after a substantial lag period, often at the expense of hypopituitarism induction and, occasionally, harmful effects on cranial nerves and blood vessels.3 Against this backdrop, pasireotide is being investigated as a potential addition to the therapeutic armamentarium for acromegaly. Pasireotide is a somatostatin receptor (SSTR) agonist with expanded specificity, engaging several receptor isoforms (SSTR1, SSTR2, SSTR3 and SSTR5).4 Activation of SSTR5 by pasireotide is thought to be particularly important for its pharmacodynamic effects, accounting for its potent suppression of growth hormone secretion. Findings from previous studies have suggested that acute administration of short-acting pasireotide suppresses growth hormone secretion in a subset of patients that show no response to octreotide administration.5 In The Lancet Diabetes & Endocrinology, an international team of investigators report on the results of a phase 3 trial comparing two doses of long-acting pasireotide with either octreotide long-acting release or lanreotide depot in 198 patients with acromegaly who were known to be refractory to the older somatostatin receptor agonists.6 In this study, pasireotide was significantly more efficacious than the two other compounds, both with regard to achievement of biochemical control (ten [15%] patients in the pasireotide 40 mg group and 13 [20%] in the pasireotide 60 mg group, vs no patients
in the control group had normalised growth hormone and IGF-1 concentrations; p=0·0006 for the 40 mg group and p
Acromegaly has attracted substantial interest among scientists and pharmaceutical researchers in the past few decades, leading to the development and licensing of several efficacious drugs in many countries, including octreotide and its long-acting formulation, lanreotide depot, and pegvisomant.1 Additionally, dopamine agonists, particularly cabergoline, also show useful activity in a subset of patients with acromegaly and have been used off label.1 The availability of a growing number of medical therapies for acromegaly is good news for both patients and their physicians. Although transsphenoidal pituitary surgery is becoming increasingly sophisticated with the availability of neuronavigation, endoscopes, and intraoperative MRI, a substantial proportion of patients do not achieve disease remission, particularly those with macroadenomas or locally invasive pituitary tumours.2 Furthermore, radiotherapy leads to disease remission after a substantial lag period, often at the expense of hypopituitarism induction and, occasionally, harmful effects on cranial nerves and blood vessels.3 Against this backdrop, pasireotide is being investigated as a potential addition to the therapeutic armamentarium for acromegaly. Pasireotide is a somatostatin receptor (SSTR) agonist with expanded specificity, engaging several receptor isoforms (SSTR1, SSTR2, SSTR3 and SSTR5).4 Activation of SSTR5 by pasireotide is thought to be particularly important for its pharmacodynamic effects, accounting for its potent suppression of growth hormone secretion. Findings from previous studies have suggested that acute administration of short-acting pasireotide suppresses growth hormone secretion in a subset of patients that show no response to octreotide administration.5 In The Lancet Diabetes & Endocrinology, an international team of investigators report on the results of a phase 3 trial comparing two doses of long-acting pasireotide with either octreotide long-acting release or lanreotide depot in 198 patients with acromegaly who were known to be refractory to the older somatostatin receptor agonists.6 In this study, pasireotide was significantly more efficacious than the two other compounds, both with regard to achievement of biochemical control (ten [15%] patients in the pasireotide 40 mg group and 13 [20%] in the pasireotide 60 mg group, vs no patients
in the control group had normalised growth hormone and IGF-1 concentrations; p=0·0006 for the 40 mg group and p
