Peptides›Cognitive, Metabolic›Pasireotide

Pasireotide

/ Multireceptor somatostatin analog; cyclohexapeptide; binds SSTR1, SSTR2, SSTR3, and SSTR5 with high affinity (broader profile than octreotide which is selective for SSTR2)

TIER 1 · ClinicalN = 0 · TESTING PENDINGMW 1047.20 g·mol⁻¹

ALIAS · Signifor (trade) · Signifor LAR (trade) · SOM230

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · 1047.20CLASS · Multireceptor somatostatin analog; cyclohexapeptide; binds SSTR1, SSTR2, SSTR3, and SSTR5 with high affinity (broader profile than octreotide which is selective for SSTR2)CATEGORY · Cognitive, Metabolic

Tier 1. FDA-approved 2012 (Signifor, subcutaneous twice-daily) for Cushing disease in adults for whom pituitary surgery is not an option or has not been curative. Signifor LAR (long-acting intramuscular formulation) approved 2014 for acromegaly in adults inadequately controlled by surgery or other somatostatin analog therapy. Multireceptor somatostatin-analog profile (SSTR1, 2, 3, 5) distinguishes it from octreotide (SSTR2-selective).

§ B · Mechanism of action

Pasireotide is a cyclohexapeptide somatostatin analog with an expanded receptor-binding profile relative to octreotide and lanreotide. Whereas octreotide is principally an SSTR2 agonist with weaker SSTR3 and SSTR5 engagement, pasireotide binds SSTR1, SSTR2, SSTR3, and SSTR5 with high affinity (notably SSTR5, which is highly expressed on corticotrophs in Cushing disease — the mechanistic basis for the Cushing indication). The broader receptor profile underlies both the Cushing efficacy and a distinct adverse-event profile from selective SSTR2 agonists, particularly the hyperglycaemia signal driven by SSTR5-mediated suppression of incretin and insulin release.

§ C · Human clinical evidence

Tier 1. Pivotal Phase 3 trial in Cushing disease (Colao 2012, NEJM PASPORT-CUSHINGS) demonstrated normalisation of urinary free cortisol in a meaningful minority of subjects with persistent or recurrent Cushing disease, supporting FDA approval. Acromegaly approval (Signifor LAR) supported by Phase 3 trials versus octreotide LAR demonstrating non-inferior or superior biochemical control in inadequately controlled subjects.

§ D · Primary literature

PubMed22397653Colao A et al. — A 12-month phase 3 study of pasireotide in Cushing's disease · The New England Journal of Medicine · human-phase-3-rctTwelve-month pasireotide normalised urinary free cortisol in approximately 15-26% of subjects with persistent or recurrent Cushing disease across two dose arms; pivotal trial supporting FDA approval. Hyperglycaemia and diabetes-related adverse events were the most common signals.Limitations: Single-pivotal-trial design; modest absolute response rate; hyperglycaemia complicates risk-benefit in selected populations.2012

PubMed11980628Bruns C et al. — SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile · European Journal of Endocrinology · in-vitroOriginal receptor-pharmacology characterisation of SOM230 (pasireotide) demonstrating high-affinity binding to human SSTR1, 2, 3, and 5 and a broader inhibitory profile than octreotide on GH and IGF-1 release in cell systems.Limitations: In-vitro receptor binding and cell-system data; clinical translation established by later Phase 3 trials.2002

§ F · Safety signal

Pasireotide-specific hyperglycaemia is the dominant differentiating safety signal versus octreotide, attributable to broader SSTR5 engagement at pancreatic islets. Class concerns shared with other somatostatin analogs include cholelithiasis, bradycardia, gastrointestinal effects, and injection-site reactions. Pre-existing diabetes is not a contraindication but requires active glucose monitoring and management.

§ H · Regulatory status

Regulatory status

FDA status:: FDA-approved
Compounding:: Not eligible for compounding (approved, not in shortage)

§ I · Notable gaps and controversies

The hyperglycaemia profile complicates use in subjects with pre-existing glucose intolerance and has driven combination-dosing studies with metformin or DPP-4 inhibitors. The molecule is supplied through prescription channels for the FDA-approved indications and is not interchangeable with vendor-sold somatostatin-analog research peptides.