SIGNIFOR LAR (pasireotide) for injectable suspension Signifor

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In a study with patients inadequately controlled with a first-generation SSA... PATIENTS WHO SWITCHED TO SIGNIFOR LAR WERE MORE LIKELY TO REACH BIOCHEMICAL CONTROL3

SIGNIFOR LAR was directly compared with octreotide LAR and lanreotide autogel23

A prospective, multicenter, randomized, parallel-group, phase 3 study in patients who were inadequately controlled* with and switched from a first-generation SSA23

Illustration of study design
Illustration of study design

Study Design: A multicenter, randomized, three-arm study conducted in patients with acromegaly inadequately controlled on a first-generation SSA. Patients were randomized to double-blind SIGNIFOR LAR 40 mg (n=65) or SIGNIFOR LAR 60 mg (n=65) or to continued open-label pretrial SSA therapies at maximal or near maximal doses (n=68). A total of 181 patients completed the 6-month trial.23

*Inadequately controlled acromegaly defined as GH >2.5 μg/L; IGF-1 >1.3 ULN.

Patients inadequately controlled on another SSA who switched to SIGNIFOR LAR treatment were more likely to experience biochemical control than those who remained on their previous SSA3

Clinical trial chart data
Clinical trial chart data

†Defined as mean GH concentration <2.5 μg/L and normalized IGF-1 concentration (between the upper and the lower limits of normal).
‡Primary endpoint (patients with IGF-1 < lower limit of normal [LLN] were not considered as “responders”).
§For one active comparator, the maximum approved US dose was not used, but most patients received the most common US dose for acromegaly.

IGF-1 and GH Reduction

SIGNIFOR LAR reduced IGF-1 and GH in patients previously inadequately controlled on a first-generation SSA23,II

Mean Reduction in IGF-1 and GH charts Mean Reduction in IGF-1 and GH charts
Tumor Reduction

Additional reductions in tumor volume were seen in some patients who switched to SIGNIFOR LAR23,¶

The proportion of patients with >25% reduction in tumor volume was assessed at 6 months (N=198)

Chart of proportion of patients with reduction in tumor volume >25%
Chart of proportion of patients with reduction in tumor volume >25%

¶In a prospective, multicenter, randomized, parallel-group, phase 3 study in patients who were inadequately controlled with and switched from a first-generation SSA.23

Adverse events documented in patients (≥10%) previously treated with other SSA

Adverse reactions chart Adverse reactions chart

#Diabetes mellitus includes the terms diabetes mellitus and type 2 diabetes mellitus.
SEE SECTION 6.1 IN FULL PRESCRIBING INFORMATION FOR COMPLETE ADVERSE REACTION TABLE.

INDICATIONS AND USAGE

SIGNIFOR LAR® (pasireotide) is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option.

IMPORTANT SAFETY INFORMATION

Hyperglycemia, Diabetes, and Ketoacidosis: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. Monitor glucose levels as clinically appropriate during therapy. There have been postmarketing cases of ketoacidosis with SIGNIFOR LAR in patients with or without history of diabetes. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia. Patients who develop significant hyperglycemia on SIGNIFOR LAR may require initiation of anti-diabetic treatment or adjustment in their current anti-diabetic treatment. The optimal treatment for the management of SIGNIFOR LAR-induced hyperglycemia is not known. If hyperglycemia cannot be controlled despite medical management, reduce the dose or discontinue SIGNIFOR LAR. Patients who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of diabetes history. If ketoacidosis is suspected, discontinue SIGNIFOR LAR and promptly evaluate and treat the patient.

INDICATIONS AND USAGE

SIGNIFOR LAR® (pasireotide) is a somatostatin analog indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option.

IMPORTANT SAFETY INFORMATION

Hyperglycemia, Diabetes, and Ketoacidosis: SIGNIFOR LAR can cause increases in blood glucose levels which are sometimes severe. Monitor glucose levels as clinically appropriate during therapy. There have been postmarketing cases of ketoacidosis with SIGNIFOR LAR in patients with or without history of diabetes. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia. Patients who develop significant hyperglycemia on SIGNIFOR LAR may require initiation of anti-diabetic treatment or adjustment in their current anti-diabetic treatment. The optimal treatment for the management of SIGNIFOR LAR-induced hyperglycemia is not known. If hyperglycemia cannot be controlled despite medical management, reduce the dose or discontinue SIGNIFOR LAR. Patients who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of diabetes history. If ketoacidosis is suspected, discontinue SIGNIFOR LAR and promptly evaluate and treat the patient.

Bradycardia and QT Prolongation: Bradycardia has been reported with the use of SIGNIFOR LAR. Patients with cardiac disease and/or risk factors for bradycardia, such as history of clinically significant bradycardia, high grade heart block, or concomitant use of drugs associated with bradycardia, should be monitored. Adjustments in the dose of drugs known to slow the heart rate (e.g., beta-blockers, calcium channel blockers) and correction of electrolyte disturbances may be necessary when initiating or during the course of SIGNIFOR LAR treatment. In cardiac electrophysiology studies with pasireotide via subcutaneous route, QT prolongation occurred at therapeutic and supra-therapeutic doses. Use with caution in patients at significant risk; evaluate ECG and electrolytes prior to dosing and periodically while on treatment. Hypokalemia or hypomagnesemia must be corrected prior to initiating SIGNIFOR LAR and should be monitored periodically during therapy.

Liver Test Elevations: Increases in liver enzymes have been observed with SIGNIFOR LAR. Evaluate liver enzyme tests prior to and during treatment.

Cholelithiasis and Complications of Cholelithiasis: There have been reports of cholelithiasis resulting in complications including cholecystitis or cholangitis and requiring cholecystectomy in patients taking SIGNIFOR LAR. Monitor periodically. Discontinue SIGNIFOR LAR if complications of cholelithiasis are suspected and treat appropriately.

Pituitary Hormone Deficiency(ies): Suppression of anterior pituitary hormones may occur on SIGNIFOR LAR. Monitor for occurrence periodically and treat if clinically indicated.

Steatorrhea and Malabsorption of Dietary Fats: New onset steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss may occur. If new occurrence or worsening of these symptoms are reported, evaluate for potential pancreatic exocrine insufficiency.

The most common adverse reactions occurring in ≥ 20% of patients with acromegaly were diarrhea, hyperglycemia, cholelithiasis, and diabetes mellitus.

To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy.

SIGNIFOR LAR® (pasireotide) for injectable suspension, for intramuscular use, is available as 10 mg, 20 mg, 30 mg, 40 mg, and 60 mg powder in a vial to be reconstituted with the provided 2 mL diluent.

Please see the accompanying full Prescribing Information and Patient Information.

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