Pasireotide (Signifor(®)) is a new subcutaneous
somatostatin analogue that acts via
somatostatin receptors to inhibit the secretion of
corticotropin from the
pituitary adenoma in patients with
Cushing's disease.
Pasireotide has a receptor binding profile that is distinct from that of other
somatostatin analogues, binding with high affinity to
somatostatin receptor subtype 5, which is strongly over expressed in
corticotroph adenoma cells.
Pasireotide is the first pituitary-directed agent to be approved for use in
Cushing's disease. In a phase III clinical trial in patients with
Cushing's disease, twice-daily
pasireotide 600 or 900 μg for 6 months led to normalization of urinary free
cortisol (UFC) levels in up to a quarter of all patients (primary endpoint) and significantly reduced mean UFC levels. The reduction in UFC levels is rapid (within one to two months) and sustained (up to 24 months). Most patients who do not have an early response to
pasireotide do not respond at a later time point. Decreases in UFC levels achieved during
pasireotide treatment are accompanied by decreases in serum and salivary
cortisol levels, as well as improvements in clinical signs and symptoms, including
body weight, blood pressure and health-related quality-of-life.
Pasireotide has a generally similar tolerability profile to that of other
somatostatin analogues, but is associated with a relatively high incidence of hyperglycaemia, requiring the addition or intensification of
glucose-lowering medication in a substantial proportion of patients. Thus,
pasireotide, together with on-going patient monitoring, provides a promising new option for the medical management of
Cushing's disease.