CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`
`
`
`
`
`
`
`REMS
`
`22-341s000
`
`

`

`APPENDIX A: REMS
`
`NDA 22—341 VICTOZA (liraglutide [rDNA origin] injection)
`
`Novo Nordisk Inc.
`
`100 College Road West, Princeton, NJ 08540
`
`Contact: Mary Ann McElligott, PhD Phone: 609-987—5831
`
`RISK EVALUATION AND MITIGATION STRATEGY (REMS)
`
`I.
`
`GOAL
`
`0 To inform providers about the risk of acute pancreatitis (including necrotizing pancreatitis)
`
`and the potential risk of medullary thyroid carcinoma associated with Victoza®.
`
`0 To inform patients about the serious risks associated with Victoza®.
`
`II.
`
`REMS ELEMENTS
`
`A. Medication Guide
`
`.
`
`A Medication Guide will be dispensed with each VICTOZA prescription. VICTOZA is dispensed
`
`in cartons containing either two or three pre-filled disposable pens with cartridges that can deliver
`
`doses of 0.6 mg, 1.2 mg, or 1.8 mg. A copy of the Medication Guide will be packaged in each
`carton. Therefore, Novo Nordisk will meet the requirements of 21 CFR 208.24 for distribution
`
`and dispensing of the Medication Guide.
`
`Additional copies of the Medication Guide willbe available via the product website
`
`(www.victoza.com), by request through the Sponsor’s toll-free information number (1-877-484—
`
`2869), and through the sponsor’s sales representatives and Medical Science Liaisons (MSLs).
`
`Please see the appended Medication Guide.
`
`B. Communication Plan V
`
`In accordance with FDCA 505-1(e)(3), Novo Nordisk will implement the following elements of a
`
`communication plan to healthcare providers (HCP) likely to prescribe VICTOZA:
`
`

`

`i. A Dear HCP (DHCP) Letter addressing the potential risk of medullary thyroid tumors
`
`and the risk of acute pancreatitis and appropriate patient selection will be mailed to HCP.
`
`The timing of the mailing will be within 60 days after product approval. The DHCP Letter
`
`will contain the FDA-approved labeling. The intended audience for this DHCP letter will
`
`be healthcare professionals who are likely to prescribe VICTOZA and all endocrinology
`
`specialists and others identified through professional organizations (e.g. AMA, AACE).
`
`These include physicians, nurse practitioners, and physicians’ assistants, predominantly in
`
`the specialties of Endocrinology, Internal Medicine, and Family Practice. Any newly
`
`identified (through 3 years after product approval) prescribers of Victoza will be fully
`
`detailed on the contents of the Communication Plan.
`
`Please see the appended Dear Healthcare Professional Letter.
`
`ii. A Direct Mail Letter containing the information included in the DHCP letter will also
`
`be mailed once per year post launch for a total of 3 years to all prescribers who are likely
`
`to prescribe VICTOZA.
`
`Please see the appended Direct Mail Letter.
`
`iii. The Highlighted Information for Prescribers will be distributed by Novo Nordisk
`
`representatives during the first discussion of VICTOZA with all HCPs visited during the
`
`first six months after product launch. The Highlighted Information for Prescribers will also
`
`be sent with the Direct Mail Letter.
`
`Please see the appended Highlighted Information for Prescribers.
`
`Novo Nordisk will make the REMS, the DHCP letter, the Medication Guide, the Highlighted
`
`Information for Prescribers, and professional labeling available via a REMS-specific linkage
`
`from the VICTOZA website. The Medication Guide, the Highlighted Information for
`
`Prescribers and professional labeling will also be available via hardcopy from Novo Nordisk
`
`representatives and through Novo Nordisk’s Call Center.
`
`Please see the appended Victoza REMS landing page screenshot.
`
`C. Elements to Assure Safe Use
`
`The RBMS for VICTOZA can be approved without Elements to Assure Safe Use.
`
`

`

`D. Implementation System
`
`Because the REMS for VICTOZA can be approved without Elements to Assure Safe Use, an
`
`implementation system is not required.
`
`E. Timetable for Submission of Assessments
`
`Novo Nordisk will submit REMS Assessments to FDA at 1 year, 2 years, 3 years, and 7 years
`
`from the date of the approval of the REMS. To facilitate inclusion of as‘much information as
`
`possible while allowing reasonable time to prepare the submission, the reporting interval covered
`
`by each assessment should conclude no earlier than 60 days-before the submission date for that
`
`assessment. Novo Nordisk will submit each assessment so that it will be received by the FDA on
`
`or before the due date.
`
`

`

`APPENDIX B: DEAR HEALTHCARE PROFESSIONAL LETTER
`
`IMPORTANT DRUG WARNING
`
`Dear Healthcare Professional:
`
`The purpose of this letter is to inform you of important safety information about Victoza. The
`Food and Drug Administration (FDA) has approved VICTOZA (liraglutide [rDNA origin] injection),
`a once daily human GLP—1 receptor agonist for the treatment of type 2 diabetes mellitus.
`VICTOZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults
`with type 2 diabetes mellitus.
`
`FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary to
`ensure that the benefits of VICTOZA outweigh the potential risk of medullary therid carcinoma
`and the risk of acute pancreatitis. Novo Nordisk has established an informational program for
`healthcare professionals to help minimize these risks.
`
`There is a Boxed Warning for VICTOZA:
`
`
`
`WARNING: RISK OF THYROID C-CELL TUMORS
`Liraglutide causes dose-dependent and treatment-duration—dependent thyroid C-cell tumors at
`
`clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza
`causes thyroid C—cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human
`relevance could not be ruled out by clinical or nonclinical studies. Victoza is contraindicated in
`
`patients with a personal or family history of MTC and in patients with Multiple Endocrine
`
`Neoplasia syndrome type 2 (MEN2). Based on the findings in rodents, monitoring with serum
`
`calcitonin or thyroid ultrasound was performed during clinical trials, but this may have increased
`
`the number of unnecessary thyroid surgeries. It is unknown whether monitoring with serum
`
`calcitonin or thyroid ultrasound will mitigate human risk of thyroid C-cell tumors. Patients should
`be counseled regarding the risk and symptoms of thyroid tumors.
`
`
`.
`
`Patients 'with thyroid nodules noted on physical examination or neck imaging obtained for
`other reasons should be referred to an endocrinologist for further evaluation.
`0 Although routine monitoring of serum calcitonin is of uncertain value in patients treated with
`VICTOZA, if serum calcitonin is measured and found to be elevated, the patient should be
`referred to an endocrinologist for further evaluation.
`
`_
`
`l'!'
`!E
`Ii!
`5.!
`.
`In clinical trials studying VICTOZA, there were more cases of pancreatitis with VICTOZA than
`with comparators.
`. After initiation of VICTOZA, and after dose increases, observe patients carefully for signs and
`symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to
`the back, and which may or may not be accompanied by vomiting).
`If pancreatitis is suspected, VICTOZA and other potentially suspect drugs should be
`discontinued promptly, confirmatory tests should be performed and appropriate management
`should be initiated.
`
`-
`
`If pancreatitis is confirmed, VICTOZA should not be restarted.
`-
`. Use with caution in patients with a history of pancreatitis.
`
`

`

`Apprgpriagg Patient figlgcgion
`. VICTOZA is contraindicated in patients with a personal or family history of medullary thyroid
`carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
`. VICTOZA is not recommended as first-line therapy for patients who have inadequate
`glycemic control on diet and exercise.
`0 VICTOZA has not been studied sufficiently in patients with a history of pancreatitis to
`determine whether these patients are at increased risk for pancreatitis while using Victoza.
`Use with caution in patients with a history of pancreatitis.
`o VICTOZA should not be used in patients with type 1 diabetes mellitus or for the treatment of
`diabetic ketoacidosis.
`
`. VICTOZA has not been studied in combination with insulin.
`
`Agvgrgg Events
`
`Healthcare professionals should report any serious adverse events thought to be associated with
`VICTOZA use to:
`
`-
`.
`
`NOVO Nordisk at 1-877-4-VICTOZA (1-877-484-2869)
`FDA’s MedWatch reporting system:
`0 By phone at 1—800—FDA—1088 (1—800-332-1088)
`0
`by facsimile at 1-800-FDA-0178 (1-800—332—0178)
`0
`by mail using FDA Form 3500
`0
`online (http:[[wwwfda.govzmedwatchlindex.html)
`
`Sincerely,
`
`Alan C. Moses, M.D.
`
`Global Chief Medical Officer, Novo Nordisk
`Enclosure: VICTOZA Full Prescribing Information
`
`This letter has been reviewed and approved by the FDA as part of the Victoza REMS.
`
`

`

`APPENDIX C: DIRECT MAIL LETTER
`
`Dear Healthcare Professional:
`
`VICTOZA (liraglutide [rDNA origin] injection) is a once daily human GLP—1 receptor agonist for
`the treatment of type 2 diabetes mellitus. VICTOZA is indicated as an adjunct to diet and
`exercise to improve glycemic control in adults with type 2 diabetes mellitus.
`
`VICTOZA is contraindicated in patients with a personal or family history of medullary thyroid
`carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN2).
`
`Novo Nordisk would like to highlight the following information on appropriate patient selection:
`
`. VICTOZA is not recommended as first-line therapy for patients who have inadequate
`glycemic control on diet and exercise.
`‘
`_ . VICTOZA has not been studied sufficiently in patients with a history of pancreatitis to
`determine whether these patients are at increased risk for pancreatitis while using
`VICTOZA. Use with caution in patients with a history of pancreatitis.
`- VICTOZA should‘not be used in patients with type 1 diabetes mellitus or for the treatment
`of diabetic ketoacidosis.
`. VICTOZA has not been studied in combination with insulin.
`
`Novo Nordisk wishes to remind you of important information concerning VICTOZA related to:
`
`-
`.
`
`potential risk of medullary thyroid carcinoma
`risk of acute pancreatitis
`
`Please take time to read the attached document. Please refer to the Full Prescribing Information
`for further product information.
`
`We invite you to contact our Novo Nordisk Customer Care Center at 1-877—4-VICTOZA (1-877—
`484—2869) if you have any questions about the information contained in this letter or in the.
`attached overview.
`
`Sincerely,
`
`Alan C. Moses, M.D., Global Chief Medical Officer, Novo Nordisk
`
`Enclosures: VICTOZA Full Prescribing Information, “Potential Risk of Medullary Thyroid
`Carcinoma and Risk of Pancreatitis” document
`
`This letter has been reviewed and approved by the FDA as part of the Victoza REMS.
`
`

`

`APPENDIX D: HIGHLIGHTED INFORMATION FOR PRESCRIBERS
`
`VICTOZA (Iiraglutide [rDNA origin] injection)
`
`Highlighted Information for Prescribers
`This information is being provided to prescribers of VICTOZA as part of the Risk Evaluation and
`Mitigation Strategy (REMS) plan for VICTOZA. REMS plans have been required by the US. Food
`and Drug Administration (FDA) since 2008 for certain drugs with serious risks to ensure that the
`benefits of the drug outweigh the risks of the drug.
`
`The purpose of this information is to inform prescribers of VICTOZA about the following:
`.
`potential risk of medullary thyroid carcinoma (MTC)
`.
`risk of acute pancreatitis
`
`WAG:
`
`VICTOZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults
`with type 2 diabetes mellitus.
`
`W .
`
`VICTOZA is contraindicated in patients with a personal or family history of medullary thyroid
`carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
`. VICTOZA is not recommended as first-line therapy for patients who have inadequate
`glycemic control on diet and exercise.
`. VICTOZA has not been studied sufficiently in patients with a history of pancreatitis to
`determine whether these patients are at increased risk for pancreatitis while using Victoza.
`Use with caution in patients with a history of pancreatitis
`o VICTOZA should not be used in patients with type 1 diabetes mellitus or for the treatment of
`diabetic ketoacidosis.
`'
`
`. VICTOZA has not been studied in combination with insulin.
`
`WWW
`
`There is a Boxed Warning for VICTOZA:
`
`
`
`WARNING: RISK OF THYROID C-CELL TUMORS
`Liraglutide causes dose-dependent and treatment-duration—dependent thyroid C-ceil tumors at
`
`
`clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza
`
`
`causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as
`
`human relevance could not be ruled out by clinical or nonclinical studies. Victoza is
`contraindicated in patients with a personal or family history of MTC and in patients with Multiple
`Endocrine Neoplasia syndrome type 2 (MEN2). Based on the finding in rodents, monitoring with
`
`serum calcitonin or thyroid ultrasound was performed during clinical trials, but this may have
`increased the number of unnecessary thyroid surgeries. It is unknown whether monitoring with
`
`serum calcitonin or thyroid ultrasound will mitigate human risk of thyroid C-cell tumors. Patients
`
`should be counseled regarding the risk and symptoms of thyroid tumors.
`
`
`
`
`
`
`
`
`-
`
`Patients with thyroid nodules noted on physical examination or neck imaging obtained for
`other reasons should be referred to an endocrinologist for further evaluation.
`. AlthOUQh routine monitoring of serum calcitonin is of uncertain value in patients treated with
`Victoza, if serum calcitonin is measured and found to be elevated, the patient should be
`referred to an endocrinologist for further evaluation.
`
`

`

`3:515 9: mm: PANQREATITIS
`
`VICTOZA labeling contains a warning describing the risk of acute pancreatitis:
`
`There are no conclusive data establishing a risk of pancreatitis with VICTOZA treatment.
`0 After initiation of VICTOZA, and after dose increases, observe patients carefully for signs and
`symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to
`the back, and which may or may not be accompanied by vomiting).
`If pancreatitis is suspected, VICTOZA and other potentially suspect drugs should be
`discontinued promptly, confirmatory tests should be performed and appropriate management
`should be initiated.
`If pancreatitis is confirmed, VICTOZA should not be restarted.
`.
`. Use with caution in patients with a history of pancreatitis.
`
`.
`
`Refer to the Full Prescribing Information for further product information.
`
`If you have any questions about these materials, please call the Novo Nordisk Customer Care
`Center at 1-877—484-2869.
`
`This brochure has been reviewed and approved by the FDA as part of the Victoza
`REMS.
`
`

`

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`

`Application
`Type/Number
`
`Submission
`Type/Number
`
`Submitter Name
`
`Product Name
`
`NBA-22341
`
`ORlG-1
`
`NOVO NORDISK
`INC
`
`VICTOZA (LIRAGLUTlDE)
`
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`
`CURTIS J ROSEBRAUGH
`
`01/25/2010
`
`