Pasireotide
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Pan-somatostatin receptor analog with preferential SSTR5 affinity; FDA-approved for Cushing's disease and acromegaly resistant to first-generation somatostatin analogs.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | Signifor, Signifor LAR, SOM230, pasireotide diaspartate |
| Category | Somatostatin analog (pan-receptor, SSTR5-preferring) |
| Sequence | Cyclo[{4-(NH2-C2H4-NH-CO-O-)Pro}-Phg-D-Trp-Lys-Tyr(4-Bzl)-Phe] |
| Molecular Weight | ~1047.19 Da |
| Molecular Formula | C58H66N8O9 |
| PubChem CID | 9941444 |
| Administration | SubQ (Signifor BID), IM (Signifor LAR monthly) |
| Typical Dose Range | SubQ: 300-900 mcg BID; LAR: 10-60 mg IM q28d |
| Half-Life | ~12 hours (SubQ); ~16-19 days (LAR) |
| Storage | Refrigerate (2-8C); protect from light |
| FDA Status | Approved (2012) — Signifor for Cushing's disease; (2014) Signifor LAR for acromegaly |
| WADA Status | Not listed |
Mechanism of Action
Pasireotide is a cyclohexapeptide somatostatin analog with a unique multi-receptor binding profile that distinguishes it from first-generation analogs (octreotide, lanreotide). While octreotide and lanreotide bind primarily to SSTR2, pasireotide has its highest affinity for SSTR5 (~40-fold greater than octreotide), with significant binding to SSTR1, SSTR2, and SSTR3 as well.
This SSTR5 selectivity is the key to pasireotide's efficacy in Cushing's disease. Corticotroph adenomas (which cause Cushing's disease by overproducing ACTH) predominantly express SSTR5 rather than SSTR2. By activating SSTR5 on corticotroph tumor cells, pasireotide suppresses ACTH secretion, which in turn reduces cortisol production. The Phase III trial (PMID 22397653) demonstrated UFC normalization in 15-26% of patients and median UFC reduction of ~48%.
For acromegaly, pasireotide's broader SSTR binding profile enables biochemical control in patients who have failed SSTR2-selective agents. The PAOLA trial (PMID 25260838) showed that 15-20% of octreotide/lanreotide-resistant patients achieved biochemical control with pasireotide LAR vs 0% with continued first-generation therapy.
However, SSTR5 activation in pancreatic beta cells suppresses insulin secretion, causing significant hyperglycemia in 73% of patients — the major safety concern with this drug. This is a direct mechanistic consequence of SSTR5 selectivity and requires proactive glucose monitoring and often concomitant antidiabetic therapy.
Key Research Areas
- Cushing's disease — First pituitary-directed medical therapy specifically approved; UFC normalization in 15-26% of patients; ~48% median UFC reduction (PMID 22397653)
- Acromegaly (second-line) — PAOLA trial: 15-20% biochemical control in octreotide/lanreotide-resistant patients vs 0% with continued SSA (PMID 25260838)
- Once-monthly LAR formulation — ~40% UFC normalization at month 7 with improved dosing convenience (PMID 29032078)
- Tumor volume reduction — Corticotroph and somatotroph adenoma shrinkage demonstrated in both indications
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 3 | Phase III Cushing's, PAOLA acromegaly, once-monthly LAR |
| Human observational | — | Post-marketing experience since 2012 |
| Systematic reviews | — | Multiple exist (not yet in vault) |
Clinical Applications
- Cancer Adjunct Therapy — Not a direct cancer therapy, but treats pituitary adenomas (benign tumors)
Protocols Using This Peptide
- No Ageless Peps protocols (FDA-approved prescription drug, not a research peptide)
Ageless Peps Products
- Not sold — Pasireotide is an FDA-approved prescription medication (Signifor/Signifor LAR) manufactured by Recordati (formerly Novartis). It is not a research peptide and is not available through Ageless Peps.
Dosing Reference
FDA-Approved Dosing
| Indication | Route | Dose | Frequency | Duration | Source |
|---|---|---|---|---|---|
| Cushing's disease (initial) | SubQ | 600 mcg | BID | Titrate; max 900 mcg BID | FDA label |
| Cushing's disease (LAR) | IM | 10-30 mg | q28 days | Titrate based on UFC | FDA label |
| Acromegaly (LAR) | IM | 40-60 mg | q28 days | After octreotide/lanreotide failure | FDA label |
Cycling
Not applicable — pasireotide is prescribed as continuous therapy. Dose titration is guided by UFC levels (Cushing's disease) or GH/IGF-1 levels (acromegaly). Glucose monitoring should begin before treatment initiation and continue regularly throughout therapy.
Contraindications & Safety
- Contraindications: Hypersensitivity to pasireotide
- Common side effects: Hyperglycemia (73%) — the most significant AE; diarrhea (58%), nausea (52%), cholelithiasis (31%), headache (28%), abdominal pain (24%), fatigue (19%), diabetes mellitus (new-onset in some patients)
- Drug interactions: Cyclosporine (reduced levels); QT-prolonging drugs (additive risk); insulin and oral hypoglycemics (dose adjustment required); ketoconazole (used concomitantly in some Cushing's protocols)
- Pregnancy/nursing: Category C; contraception recommended during treatment
- Special populations: Not recommended in patients with uncontrolled diabetes mellitus; hepatic impairment may increase exposure; monitor ECG for QT prolongation
Synergistic Combinations
- Octreotide — First-line somatostatin analog; pasireotide used when octreotide fails
- Lanreotide — First-line alternative; pasireotide used when lanreotide fails
- Cabergoline — Dopamine agonist sometimes combined with pasireotide in Cushing's disease
- Ketoconazole/metyrapone — Steroidogenesis inhibitors used as combination therapy in severe Cushing's
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| 22397653 | Phase 3 study of pasireotide in Cushing's disease (NEJM) | 2012 | RCT |
| 25260838 | PAOLA: Pasireotide vs octreotide/lanreotide in acromegaly | 2014 | RCT |
| 29032078 | Once-monthly pasireotide LAR in Cushing's disease | 2018 | RCT |
References
- PMID 22397653 — Colao et al. Phase III pasireotide in Cushing's disease (2012)
- PMID 25260838 — Gadelha et al. PAOLA trial: pasireotide in acromegaly (2014)
- PMID 29032078 — Lacroix et al. Once-monthly pasireotide LAR (2018)
Related
FDA Disclaimer: Pasireotide (Signifor/Signifor LAR) is an FDA-approved prescription medication. The information in this note is for educational and reference purposes only and does not constitute medical advice. Prescribing and administration must be performed by qualified healthcare providers.
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