Peptide education
Pasireotide
Signifor · Signifor LAR · SOM230
Pasireotide is a somatostatin analog prescribed for certain pituitary disorders. Signifor is a short-acting subcutaneous injection for adult Cushing's disease; Signifor LAR is a long-acting intramuscular product with labeled uses in Cushing's disease and acromegaly.
In a Cushing's disease trial, urinary free cortisol was normal at month six without a dose increase in 12 of 82 patients starting 0.6 mg twice daily and 21 of 80 starting 0.9 mg twice daily. Over the 12-month study, hyperglycemia-related adverse events occurred in 118 of 162 patients.
Overview
Quick answer
Cushing's disease involves excess ACTH and cortisol; acromegaly involves excess growth hormone and IGF-1. The two pasireotide formulations differ in route, schedule and approved indications.
What is Signifor used for?
The subcutaneous product is labeled for adults with Cushing's disease when pituitary surgery is not an option or has not been curative.
What is Signifor LAR used for?
The depot is labeled for Cushing's disease when pituitary surgery is not an option or has not been curative, and for acromegaly after an inadequate surgical response or when surgery is not an option. Safety and effectiveness of the depot have not been established in pediatric patients.
How are the products given?
Signifor is injected under the skin twice daily. Signifor LAR is reconstituted and injected into a gluteal muscle by a trained healthcare professional every 28 days. Its starting dose differs between the two indications.
Why is blood sugar monitored?
Pasireotide can cause high blood glucose and diabetes, sometimes severe. Ketoacidosis has also been reported. The labels call for glucose assessment before and during treatment.
Evidence
Evidence snapshot
At month six, 12 of 82 and 21 of 80 patients in the two starting-dose groups had normal urinary free cortisol without an increased dose.
The Signifor LAR label describes controlled studies using growth hormone and IGF-1 as biochemical endpoints.
The short-acting injection is subcutaneous; the depot is injected into a muscle by a trained healthcare professional.
The labels also describe bradycardia, QT prolongation, liver test elevations, gallstones and hormone deficiencies.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| Pasireotide can lower cortisol in Cushing's disease. | In a randomized comparison of two starting doses, a minority achieved normal urinary free cortisol at month six without a dose increase. | Supported for the studied population, with variable response. |
| Both US formulations have the same acromegaly indication. | The Signifor LAR label includes acromegaly under specific surgical conditions. The short-acting Signifor label covers adult Cushing's disease. | No. Indications and administration are formulation-specific. |
| A normal cortisol result means Cushing's disease is cured. | The trial measured urinary free cortisol during treatment. It did not establish that a normal measurement represented a surgical cure. | Biochemical control during treatment is not the same as cure. |
Bottom line
Main takeaway
Pasireotide is a prescription medicine that can reduce hormone release in specific pituitary disorders.
Short-acting Signifor is injected under the skin; the LAR depot is injected into a muscle.
The Cushing's disease study compared two active starting doses without placebo; some patients were unblinded at month three and treatment was open-label after month six.
Identity
What it is
Pasireotide is a synthetic somatostatin analog that binds multiple somatostatin receptor subtypes. It suppresses hormone secretion in the labeled settings.
Signifor and Signifor LAR are separate formulations. Doses in milligrams should be interpreted with the product, route and dosing interval.
Use context
Routes, doses, and cycle patterns
The product, indication, liver function, response and tolerability affect dosing.
Human studies and product labels
Signifor for adult Cushing's disease
- Purpose
- Control of excess cortisol in the label-defined setting
- Context
- US prescribing information
- Route
- Subcutaneous injection
- Amount
- 0.6 mg or 0.9 mg initially
- Frequency
- Twice daily
The label gives a 0.3 to 0.9 mg twice-daily range and lower dosing for moderate hepatic impairment. Severe hepatic impairment is a setting to avoid.
Signifor LAR for acromegaly
- Purpose
- Biochemical control in the label-defined setting
- Context
- US prescribing information
- Route
- Intramuscular gluteal injection by a trained healthcare professional
- Amount
- 40 mg initially
- Frequency
- Every 28 days
The label describes response-based adjustments and lower starting and maximum doses with moderate hepatic impairment.
Signifor LAR for Cushing's disease
- Purpose
- Control of excess cortisol in the label-defined setting
- Context
- US prescribing information
- Route
- Intramuscular gluteal injection by a trained healthcare professional
- Amount
- 10 mg initially
- Frequency
- Every 28 days
The label describes response-based adjustment and a lower maximum dose with moderate hepatic impairment.
Cushing's disease phase 3 trial
- Purpose
- Urinary free cortisol control
- Context
- Randomized comparison of two active starting doses
- Route
- Subcutaneous injection
- Amount
- 0.6 mg or 0.9 mg
- Frequency
- Twice daily
- Duration
- Primary endpoint at month 6; follow-up through month 12
Some patients were unblinded for dose escalation at month three; treatment after month six was open-label. The primary endpoint required normal cortisol without a dose increase.
Research
Research evidence
The Cushing's disease study compared two subcutaneous starting doses without placebo. Some patients were unblinded at month three; treatment after month six was open-label. The LAR label describes separate acromegaly studies using biochemical measures of growth hormone and IGF-1.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Cushing's disease phase 3 trial | 162 adults with urinary free cortisol at least 1.5 times the upper limit of normal | Randomized starting-dose comparison, initially double-blind, with some unblinding at month three and an open-label period after month six | Subcutaneous pasireotide 0.6 mg or 0.9 mg twice daily | At month six, 12 of 82 and 21 of 80 had normal urinary free cortisol without an increased dose. | No placebo group; some patients were unblinded before the primary endpoint, response was not universal, and hyperglycemia was common. | Randomized dose comparison |
| Signifor LAR acromegaly studies | Patients with acromegaly in the product label's study populations | Controlled clinical studies summarized in US prescribing information | Long-acting intramuscular pasireotide | The studies assessed biochemical control using growth hormone and IGF-1. | The depot findings do not establish an acromegaly indication for the short-acting product. | Controlled, formulation-specific |
Cautions
Safety and unknowns
- Blood glucose can rise substantially; diabetes and ketoacidosis have been reported. Glucose and HbA1c assessment is part of baseline and ongoing care.
- Bradycardia and QT prolongation can occur. The labels describe ECG and electrolyte assessment, particularly in patients with cardiac risk factors.
- Liver test elevations, gallstones and pituitary hormone deficiencies are described. Excess cortisol suppression can cause hypocortisolism.
- The depot label also warns about steatorrhea and malabsorption of dietary fat.
Mechanism
How it is proposed to work
Pasireotide binds somatostatin receptors that help regulate hormone secretion.
In Cushing's disease, reducing ACTH secretion can lower adrenal cortisol production.
In acromegaly, the depot can reduce growth hormone secretion and IGF-1 levels.
Details
Technical details
Sources
References
- 1.
DailyMed. Signifor prescribing information
US label for the twice-daily subcutaneous formulation in adult Cushing's disease.
- 2.
DailyMed. Signifor LAR prescribing information
US label for the intramuscular depot in specified acromegaly and Cushing's disease settings.
- 3.
PubMed. A 12-month phase 3 study of pasireotide in Cushing's disease
doi:10.1056/NEJMoa1105743 PMID:22397653 NCT00434148
Randomized trial of two subcutaneous starting doses in adults with Cushing's disease.