About Somatuline® Depot (lanreotide) | HCP

Progression-Free Survival (PFS) in Patients With GEP-NETs^*

For unresectable, well- or moderately-differentiated, locally advanced or metastatic GEP-NETs

The efficacy of Somatuline Depot was tested in a phase III, 96-week, international, randomized, double-blind, placebo-controlled trial called CLARINET.^1,2†

At the end of 22 months, the median PFS was not yet reached for Somatuline Depot compared to 16.6 months for placebo (95% CI: 11.2-22.1)^¹

Number of events (%)

Somatuline Depot=32 (31.7)
Placebo=60 (58.3)

The efficacy of Somatuline Depot was studied in 204 patients with unresectable, well- or moderately-differentiated, metastatic or locally advanced, gastroenteropancreatic neuroendocrine tumors. Patients were required to have nonfunctioning tumors without hormone-related symptoms.¹

For additional information about the study methodology, please see Study Design and Patient Information below.

Adverse Reactions Reported in CLARINET Study

Most common adverse reactions (greater than 10%) are abdominal pain, musculoskeletal pain, vomiting, headache, injection site reaction, hyperglycemia, hypertension, and cholelithiasis.^¹ Please see Adverse Reactions below for more information about these possible side effects. Please tap or click here to review the full Important Safety Information for Somatuline Depot.

_{*GEP-NETs=gastroenteropancreatic neuroendocrine tumors.}
_{†CLARINET=Controlled Study of Lanreotide Antiproliferative Response In NeuroEndocrine Tumors.}

PFS in GEP-NETs

Study Design and Patient Information

CLARINET^*: A Phase III Pivotal Trial

The majority (84%) of patients in CLARINET had not received prior pharmacologic therapy for GEP-NETs. Some patients (16%) received prior therapy²
Patients were excluded if they received²:
- Somatostatin analog at any time, unless they received it >6 months prior to study entry and for <15 days
- Interferon, chemoembolization, or chemotherapy: <6 months prior to study entry

^*CLARINET=Controlled Study of Lanreotide Antiproliferative Response In NeuroEndocrine Tumors.

^†Administered every 28 days by deep subcutaneous injection. Follow-up visits occurred at Weeks 12, 24, 36, 48, 72, 96.

^‡Assessed by a central independent radiological review in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

Disease Characteristics

CLARINET included patients with unresectable, well- to moderately-differentiated, locally advanced or metastatic GEP-NETs, a range of hepatic tumor loads, and varying primary tumor locations (foregut/pancreas, midgut, or hindgut).^1,2

Baseline prognostic characteristics were similar between arms with one exception: There were 39% of patients in the Somatuline Depot arm and 27% of patients in the placebo arm who had hepatic involvement by tumor of >25%.¹

Adverse Reactions

CLARINET: Adverse Reactions

_{ᵃ Includes preferred terms of abdominal pain, abdominal pain upper/lower, abdominal discomfort.}
_{ᵇ Includes preferred terms of myalgia, musculoskeletal discomfort, musculoskeletal pain, back pain.}
_{ᶜ Includes preferred terms of infusion site extravasation, injection site discomfort, injection site granuloma, injection site hematoma, injection site hemorrhage, injection site induration, injection site mass, injection site nodule, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling.}
_{ᵈ Includes preferred terms of diabetes mellitus, glucose tolerance impaired, hyperglycemia, type 2 diabetes mellitus.}
_{ᵉ Includes preferred terms of hypertension, hypertensive crisis.}
_{ᶠ Includes preferred terms of depression, depressed mood.}
_{^*Includes one or more serious adverse events (SAEs) defined as any event that results in death, is life-threatening, results in hospitalization or prolongation of hospitalization, results in persistent or significant disability, results in congenital anomaly/birth defect, or may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed.}
_{^†Defined as hazardous to well-being, significant impairment of function or incapacitation.}

Discontinuation rates due to treatment-emergent adverse reactions¹:

5% (5/101) in the Somatuline Depot arm and 3% (3/103) in the placebo arm

Carcinoid Syndrome¹

Somatuline Depot is FDA-approved to treat adults with carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy.

The most common adverse reactions occurring in the carcinoid syndrome trial were generally similar to those in the GEP-NET trial. Adverse reactions occurring in greater than 5% of patients who received Somatuline Depot in the carcinoid syndrome trial and occurring at least 5% greater than placebo were headache (12%), dizziness (7%), and muscle spasm (5%).

Carcinoid Syndrome

Deep Subcutaneous Injection and Formulation^1,4-6

Redesigned Delivery System*

You demanded more and we acted. From a prefilled syringe to a more ergonomic design, the redesigned Somatuline Depot syringe retains all the features you prefer, and introduces new ones designed to help streamline administration and place added stability and control in your hands.

What helps make Somatuline Depot simple to administer?

Ready-to-use: No reconstitution required
Low injection volume
Deep subcutaneous injection

Improvements to the Somatuline Depot syringe

MOLDED TRAY protects syringe before use
PLUNGER HEAD textured design for stability
REINFORCED PLUNGER to help improve the injection process
FINGER FLANGES are wide, curved, and textured to stabilize grip
SYRINGE BODY is transparent and textured for improved grip
NEEDLE CAP is large and easy to grip

Somatuline Depot continues to offer:

Low injection volume (0.5 mL)
Transparent body for visual confirmation of delivery
Needle safety system to help minimize risk of needle-stick injuries

_{*The Somatuline Depot delivery system was updated to provide an improved ergonomic injection experience, based on user feedback. Through a series of 4 formative studies between 2015 and 2017, Ipsen sought feedback from acromegaly and NET patients, nurses and caregivers on the design and functionality of new delivery device prototypes.

These culminated in a human factors validation study in 2017 in which the final delivery system prototype was tested to determine whether the product could be safely and effectively used by intended users in the intended use environment. Key changes between the currently marketed injection system and the new injection system are: an overcap to improve the ergonomics (and needle shield removal); plunger support for the new injection system; and improved version of the needle safety system.}

Liquid Crystal Formulation

A high density of nanotubes allows for a low injection volume in the ready-to-use prefilled syringe. It is believed that lanreotide forms a depot that functions as a reservoir for the drug between extended doses¹^,⁴
Lanreotide is slowly released, enabling once-monthly delivery via deep subcutaneous injection. Lanreotide passively diffuses toward the surrounding tissues and is absorbed into the bloodstream¹

Delivery

IMPORTANT SAFETY INFORMATION & INDICATIONS

Contraindications

SOMATULINE DEPOT is contraindicated in patients with hypersensitivity to lanreotide. Allergic reactions (including angioedema and anaphylaxis) have been reported following administration of lanreotide.

Warnings and Precautions

Cholelithiasis and Gallbladder Sludge
- SOMATULINE DEPOT may reduce gallbladder motility and lead to gallstone formation.
- Periodic monitoring may be needed.
- If complications of cholelithiasis are suspected, discontinue SOMATULINE DEPOT and treat appropriately.

Hypoglycemia or Hyperglycemia
- Patients treated with SOMATULINE DEPOT may experience hypoglycemia or hyperglycemia.
- Blood glucose levels should be monitored when SOMATULINE DEPOT treatment is initiated, or when the dose is altered, and antidiabetic treatment should be adjusted accordingly.

Cardiovascular Abnormalities
- SOMATULINE DEPOT may decrease heart rate.
- In patients without underlying cardiac disease, SOMATULINE DEPOT may lead to a decrease in heart rate without necessarily reaching the threshold of bradycardia.
- In patients suffering from cardiac disorders prior to treatment, sinus bradycardia may occur. Care should be taken when initiating treatment in patients with bradycardia.

Most Common Adverse Reactions

GEP-NETs: Adverse reactions in >10% of patients who received SOMATULINE DEPOT were abdominal pain (34%), musculoskeletal pain (19%), vomiting (19%), headache (16%), injection site reaction (15%), hyperglycemia (14%), hypertension (14%), and cholelithiasis (14%).
Carcinoid Syndrome: Adverse reactions occurring in the carcinoid syndrome trial were generally similar to those in the GEP-NET trial. Adverse reactions in ≥5% of patients who received SOMATULINE DEPOT and at least 5% greater than placebo were headache (12%), dizziness (7%) and muscle spasm (5%).

Drug Interactions

SOMATULINE DEPOT may decrease the absorption of cyclosporine (dosage adjustment may be needed); increase the absorption of bromocriptine; and require dosage adjustment for bradycardia-inducing drugs (e.g., beta-blockers).

Special Populations

Lactation: Advise women not to breastfeed during treatment and for 6 months after the last dose.

To report SUSPECTED ADVERSE REACTIONS, contact Ipsen Biopharmaceuticals, Inc. at 1-855-463-5127 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

SOMATULINE® DEPOT (lanreotide) is a somatostatin analog indicated for:

the treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival; and
the treatment of adults with carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy.

Please click here for the full Prescribing Information and Patient Information.

_{References: 1. Data on file. Basking Ridge, NJ: Ipsen Biopharmaceuticals, Inc.; 2007. 2. Wolin EM, Manon A, Chassaing C, et al. Lanreotide depot: an antineoplastic treatment of carcinoid or neuroendocrine tumors. J Gastrointest Canc. 2016;47(4):366-374. 3. Pandit A, Fay N, Bordes L, et al. Self-assembly of the octapeptide lanreotide and lanreotide-based derivatives: the role of the aromatic residues. J Pept Sci. 2008;14(1):66-75. 4. Somatuline Depot (lanreotide) Injection [Prescribing Information]. Cambridge, MA: Ipsen Biopharmaceuticals, Inc.; June 2019. 5. Adelman DT, Truong Thahn X-M, Mégret C. Enhancing patient care: co-creation and validation of a new and improved delivery system for lanreotide autogel/depot and its evaluation by US healthcare professionals. Presented at the 101st Annual Meeting and Expo of the Endocrine Society. New Orleans, LA; March 23-26, 2018. 6. Data on file. Basking Ridge, NJ: Ipsen Biopharmaceuticals, Inc.; 2018. This study has been funded by Ipsen.}

Progression-Free Survival (PFS) in Patients With GEP-NETs*