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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 022341/S-004
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`Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
`REMOVE REMS ELEMENT
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`Novo Nordisk, Inc.
`Attention: Anne Phillips, M.D.
`Corporate Vice President, CMR
`100 College Road West
`Princeton, NJ 08540
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`Dear Dr. Phillips:
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`Please refer to your Supplemental New Drug Application (sNDA) dated November 19, 2010,
`received November 19, 2010, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for VICTOZA (liraglutide [rDNA origin]) Injection.
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`We acknowledge receipt of your amendments dated December 22, 2010, January 5, April 28,
`and May 10 (2), and 17, 2011; and your risk evaluation and mitigation strategy (REMS)
`assessment dated January 25, 2011.
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`We also refer to our letter dated May 6, 2011, which required revisions to the communication
`plan of your REMS. These revisions were required because your January 25, 2011, REMS
`assessment showed that the REMS was not meeting its goal of educating health care providers
`about the potential risks associated with the use of VICTOZA (liraglutide [rDNA origin]). We
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`acknowledge receipt of your revised REMS dated May 10 and 17, 2011.
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`This supplemental NDA provides for the addition of information regarding postmarketing
`reports of worsening renal function, including acute renal failure, to the package insert and
`corresponding text in the Medication Guide, and proposed modifications to the approved REMS.
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (Physician Insert and Medication Guide)
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`Reference ID: 2948949
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` NDA 022341/S-004
`Page 2
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`with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
`supplements, as well as annual reportable changes not included in the enclosed labeling.
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`Information on submitting SPL files using eLIST may be found in the guidance for industry
`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications for this NDA, including CBE
`supplements for which FDA has not yet issued an action letter, with the content of labeling
`[21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this
`supplemental application, as well as annual reportable changes and annotate each change. To
`facilitate review of your submission, provide a highlighted or marked-up copy that shows all
`changes, as well as a clean Microsoft Word version. The marked-up copy should provide
`appropriate annotations, including supplement number(s) and annual report date(s).
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`We request that the labeling approved today be available on your website within 10 days of
`receipt of this letter.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for VICTOZA (liraglutide [rDNA origin]) was originally approved on January 25,
`2010. The REMS consisted of a Medication Guide, a communication plan, and a timetable for
`submission of assessments of the REMS.
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`Your proposed modification to the REMS consists of a request to eliminate the Medication
`Guide as an element of the approved REMS, and modifications to the communication plan to
`include a modified reminder Dear Healthcare Provider letter to be sent to the primary care
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`physician audience within 60 days of approval of the REMS modification, and a revised Direct
`Mail letter to be sent to all prescribers of VICTOZA (liraglutide [rDNA origin]) on an annual
`basis for a total of 3 years following approval of this REMS modification.
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`We have determined that maintaining the Medication Guide as part of the approved labeling is
`adequate to address the serious and significant public health concern and meets the standard in
`21 CFR 208.1 and, therefore, it is no longer necessary to include the Medication Guide as an
`element of the approved REMS to ensure that the benefits of the drug outweigh the risks.
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`Therefore, we agree with your proposal, and a Medication Guide is no longer required as part of
`the REMS for VICTOZA (liraglutide [rDNA origin]). We remind you that the Medication
`Guide will continue to be part of the approved labeling for VICTOZA (liraglutide [rDNA
`origin]) in accordance with 21 CFR 208.
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`Your proposed modified REMS, submitted on May 10 and 17, 2011, and appended to this letter,
`is approved. The modified REMS consists of a communication plan and a timetable for
`submission of assessments of the REMS.
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`Reference ID: 2948949
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` NDA 022341/S-004
`Page 3
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`The timetable for submission of assessments of the REMS will remain the same as that approved
`on January 25, 2010.
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` The revised REMS assessment plan should include, but is not limited to, the following:
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`1. Evaluation of healthcare providers’ understanding of the serious risks of VICTOZA
`(liraglutide [rDNA origin])
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`2. An assessment of healthcare providers’ awareness of:
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`a. appropriate patient population characteristics, and
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`b. the potential risk for medullary thyroid carcinoma
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`c. the need for prompt evaluation of patients who develop symptoms suggestive of
`pancreatitis
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`3. Evaluation of healthcare providers’ identification and treatment of:
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`a. medullary thyroid carcinoma after initiation of VICTOZA (liraglutide [rDNA
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`origin])
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`b. acute pancreatitis after initiation of VICTOZA (liraglutide [rDNA origin])
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`4. Evaluation of the extent to which the communication plan is meeting the goals of the
`REMS and whether modifications to the elements or goals are needed
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`5. An assessment of the number of VICTOZA (liraglutide [rDNA origin]) prescribers
`identified to receive the Dear Health Care Provider (DHCP) letter and the number of
`DHCP letters mailed
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`6. An assessment of the percentage of targeted physicians who are presented with the
`Highlighted Information for Prescribers via Sales Specialists, the website, or medical
`information department
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`7. As required under section 505-1(g)(3)(B) and (C), information on the status of any
`postapproval study or clinical trial required under section 505(o)(3) or otherwise
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`undertaken to investigate a safety issue. With respect to any such postapproval study,
`you must include the status of such study, including whether any difficulties completing
`the study have been encountered. With respect to any such postapproval clinical trial,
`you must include the status of such clinical trial, including whether enrollment has begun,
`the number of participants enrolled, the expected completion date, whether any
`difficulties completing the clinical trial have been encountered, and registration
`information with respect to requirements under subsections (i) and (j) of section 402 of
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`the Public Health Service Act. You can satisfy these requirements in your REMS
`assessments by referring to relevant information included in the most recent annual report
`required under section 506B and 21 CFR 314.81(b)(2)(vii) and including any material or
`significant updates to the status information since the annual report was prepared. Failure
`to comply with the REMS assessments provisions in section 505-1(g) could result in
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`enforcement action.
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`Reference ID: 2948949
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` NDA 022341/S-004
`Page 4
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`We remind you that in addition to the assessments submitted according to the timetable included
`in the approved REMS, you must submit a REMS assessment and may propose a modification to
`the approved REMS when you submit a supplemental application for a new indication for use as
`described in section 505-1(g)(2)(A) of FDCA.
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`If you currently distribute or plan to distribute an authorized generic product under this NDA,
`you must submit a complete proposed REMS that relates only to the authorized generic product.
`Submit a proposed REMS, REMS supporting document, and any required appended documents
`as a prior approval supplement. Approval of the proposed REMS is required before you may
`market your authorized generic product.
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`Prominently identify the submission containing the REMS assessments or proposed
`modifications of the REMS with the following wording in bold capital letters at the top of the
`first page of the submission as appropriate:
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`NDA 022341 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 022341
`PROPOSED REMS MODIFICATION
`REMS ASSESSMENT
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 022341
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on page 2 of the form. For more information about submission of
`promotional materials to the Division of Drug Marketing, Advertising, and Communications
`(DDMAC), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`Reference ID: 2948949
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` NDA 022341/S-004
`Page 5
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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`If you have any questions, please call Pooja Dharia, Pharm.D., Regulatory Project Manager, at
`(301) 796-5332.
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`Sincerely,
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`{See appended electronic signature page}
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`Mary Parks, M.D.
`Director
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`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Package Insert
`Medication Guide
`REMS
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`Reference ID: 2948949
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`MARY H PARKS
`05/18/2011
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`Reference ID: 2948949
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