Pasireotide

Pasireotide is a synthetic cyclic six-amino-acid somatostatin analog developed as SOM230. Signifor is given subcutaneously twice daily; Signifor LAR is a monthly intramuscular depot. It binds four of the five somatostatin receptor subtypes, especially subtype 5, distinguishing it from octreotide and lanreotide.

Subtype 5 is highly expressed on the corticotroph tumors responsible for Cushing disease. Receptor activation lowers ACTH secretion and therefore adrenal cortisol production. In acromegaly, broad somatostatin-receptor activity suppresses GH and IGF-1.

A 12-month Phase III Cushing study found reduced urinary free cortisol, with normalization in some patients and greater effects at the higher dose. The broader receptor profile can help when older analogs are inadequate, but insulin secretion is also reduced: glucose elevation is more pronounced than with some other somatostatin analogs.

Use concerns pituitary Cushing disease not cured by surgery or when surgery is impossible, and acromegaly inadequately controlled with surgery or other therapy. Product formulation and disease indication must remain matched.

Common effects include substantial hyperglycemia or new diabetes, diarrhea, nausea, gallstones, headache, abdominal pain and fatigue. Glucose may require active monitoring and treatment.

Other important concerns are bradycardia, QT prolongation, elevated liver enzymes and excessive cortisol suppression. A receptor-based mechanism does not remove those systemic risks.