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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 209637
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA APPROVAL
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`Novo Nordisk Inc.
`Attention: Stephanie DeChiaro
`Director Regulatory Affairs
`P.O. Box 846
`800 Scudders Mill Road
`Plainsboro, NJ 08536
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`Dear Ms. DeChiaro:
`
`Please refer to your New Drug Application (NDA) dated and received December 5, 2016, and
`your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA) for Ozempic (semaglutide) injection.
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`This new drug application provides for the use of Ozempic (semaglutide) injection as an adjunct
`to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
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`We have completed our review of this 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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`WAIVER OF HIGHLIGHTS SECTION
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`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
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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 (text for the package insert, Medication
`Guide, and instructions for use). Information on submitting SPL files using eLIST may be found
`in the guidance for industry SPL Standard for Content of Labeling Technical Qs and As,
`available at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf
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`Reference ID: 4190425
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`

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`NDA 209637
`Page 2
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`The SPL will be accessible via publicly available labeling repositories.
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and immediate container labels that are identical to the enclosed
`carton and immediate container labels as soon as they are available, but no more than 30 days
`after they are printed. Please submit these labels electronically according to the guidance for
`industry titled Providing Regulatory Submissions in Electronic Format — Certain Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(May 2015, Revision 3). For administrative purposes, designate this submission “Final Printed
`Carton and Container Labels for approved NDA 209637.” Approval of this submission by
`FDA is not required before the labeling is used.
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`EXPIRATION DATING PERIOD
`The shelf life of the drug product is 36 months at 5°C, and the in-use shelf life is 56 days at
`5°C to 30°C after initial use.
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`We are waiving the pediatric study requirement for ages 0 through 9 years (inclusive) because
`necessary studies are impossible or highly impracticable. This is because there are too few
`children in this age range with type 2 diabetes mellitus to study.
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`We are deferring submission of your pediatric study for ages 10 to 17 years (inclusive) for this
`application because this product is ready for approval for use in adults and the pediatric study has
`not been completed.
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`Your deferred pediatric study required under section 505B(a) of the FDCA is a required
`postmarketing study. The status of this postmarketing study must be reported annually according
`to 21 CFR 314.81 and section 505B(a)(3)(C) of the FDCA. This required study is listed below.
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`Reference ID: 4190425
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`

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`NDA 209637
`Page 3
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`3294-1
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`Conduct a 26-week, randomized, double-blind, placebo-controlled parallel group
`study of the safety and efficacy of Ozempic (semaglutide) for the treatment of
`type 2 diabetes mellitus in pediatric patients ages 10 to 17 years (inclusive),
`followed by a 26-week open-label, controlled extension. Background therapy will
`consist of either metformin, insulin, or metformin plus insulin.
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`Draft Protocol Submission: March 2018
`Final Protocol Submission:
`January 2019
`Study Completion:
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`December 2026
`Final Report Submission: October 2027
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`Submit the protocol to your IND 079754, with a cross-reference letter to this NDA.
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`Reports of this required pediatric postmarketing study must be submitted as a new drug
`application (NDA) or as a supplement to your approved NDA with the proposed labeling
`changes you believe are warranted based on the data derived from these studies. When
`submitting the reports, please clearly mark your submission "SUBMISSION OF REQUIRED
`PEDIATRIC ASSESSMENTS" in large font, bolded type at the beginning of the cover letter of
`the submission.
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`POSTMARKETING REQUIREMENTS UNDER 505(o)
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`Section 505(o)(3) of the FDCA authorizes FDA to require holders of approved drug and
`biological product applications to conduct postmarketing studies and clinical trials for certain
`purposes, if FDA makes certain findings required by the statute.
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`We have determined that an analysis of spontaneous postmarketing adverse events reported
`under subsection 505(k)(1) of the FDCA will not be sufficient to assess a signal of a serious risk
`of medullary thyroid carcinoma associated with Ozempic (semaglutide).
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`Furthermore, the new pharmacovigilance system that FDA is required to establish under section
`505(k)(3) of the FDCA will not be sufficient to assess this serious risk.
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`Therefore, based on appropriate scientific data, FDA has determined that you are required to
`conduct the following study:
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`Reference ID: 4190425
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`

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`Conduct a medullary thyroid carcinoma registry-based case series of at least
`15 years duration to systematically monitor the annual incidence of medullary
`thyroid carcinoma in the United States and to identify any increase related to the
`introduction of Ozempic (semaglutide) into the marketplace. This study will also
`establish a registry of incident cases of medullary thyroid carcinoma and
`characterize their medical histories related to diabetes and use of Ozempic
`(semaglutide).
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`The timetable you submitted on November 7, 2017, states that you will conduct
`this study according to the following schedule:
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`Draft Protocol Submission:
`Final Protocol Submission:
`Interim Report Submissions:
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`Study Completion:
`Final Report Submission:
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`August 2018
`February 2019
`March 2020, March 2021, March 2022,
`March 2023, March 2024, March 2025,
`March 2026, March 2027, March 2028,
`March 2029, March 2030, March 2031,
`March 2032, March 2033
`May 2034
`May 2035
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`NDA 209637
`Page 4
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`3294-2
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`Reference ID: 4190425
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`Submit clinical protocols to your IND 079754, with a cross-reference letter to this NDA. Submit
`nonclinical and chemistry, manufacturing, and controls protocols and all final reports to your
`NDA. Prominently identify the submission with the following wording in bold capital letters at
`the top of the first page of the submission, as appropriate: Required Postmarketing Protocol
`Under 505(o), Required Postmarketing Final Report Under 505(o), Required
`Postmarketing Correspondence Under 505(o).
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`Submission of the protocols for required postmarketing observational studies to your IND is for
`purposes of administrative tracking only. These studies do not constitute clinical investigations
`pursuant to 21 CFR 312.3(b) and therefore are not subject to the IND requirements under
`21 CFR part 312 or FDA’s regulations under 21 CFR parts 50 (Protection of Human Subjects)
`and 56 (Institutional Review Boards).
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`Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of any
`study or clinical trial required under this section. This section also requires you to periodically
`report to FDA on the status of any study or clinical trial otherwise undertaken to investigate a
`safety issue. Section 506B of the FDCA, as well as 21 CFR 314.81(b)(2)(vii) requires you to
`report annually on the status of any postmarketing commitments or required studies or clinical
`trials.
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`FDA will consider the submission of your annual report under section 506B and
`21 CFR 314.81(b)(2)(vii) to satisfy the periodic reporting requirement under section
`505(o)(3)(E)(ii) provided that you include the elements listed in 505(o) and
`21 CFR 314.81(b)(2)(vii). We remind you that to comply with 505(o), your annual report must
`also include a report on the status of any study or clinical trial otherwise undertaken to
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`

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`NDA 209637
`Page 5
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`investigate a safety issue. Failure to submit an annual report for studies or clinical trials required
`under 505(o) on the date required will be considered a violation of FDCA section
`505(o)(3)(E)(ii) and could result in enforcement action.
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`POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
`UNDER SECTION 506B
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`We remind you of your postmarketing commitments:
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`3294-3 Develop and validate a sensitive assay to assess the neutralizing activity of anti-
`semaglutide antibodies and its cross-neutralizing effect on native GLP-1.
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`The timetable you submitted on November 7, 2017, states that you will conduct
`this study according to the following schedule:
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`Final Report Submission:
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`November 2018
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`3294-4
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`Conduct a study to assess the incidence of neutralizing antibodies to semaglutide
`and GLP-1 in subjects treated with semaglutide using the assays developed under
`PMC 3294-3. The samples may be derived from pre-existing clinical studies.
`Sample selection criteria will be submitted to and reviewed by the Agency prior
`to initiation of sample analysis.
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`The timetable you submitted on November 7, 2017, states that you will conduct
`this study according to the following schedule:
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`Final Protocol Submission:
`Final Report Submission:
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`November 2018
`May 2019
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`Submit clinical protocols to your IND 079754, for this product. Submit nonclinical and
`chemistry, manufacturing, and controls protocols and all postmarketing final reports to this
`NDA. In addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a
`status summary of each commitment in your annual report to this NDA. The status summary
`should include expected summary completion and final report submission dates, any changes in
`plans since the last annual report, and, for clinical studies/trials, number of patients entered into
`each study/trial. All submissions, including supplements, relating to these postmarketing
`commitments should be prominently labeled “Postmarketing Commitment Protocol,”
`“Postmarketing Commitment Final Report,” or “Postmarketing Commitment
`Correspondence.”
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`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENTS
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`We acknowledge receipt of your submission dated December 5, 2016, of a proposed risk
`evaluation and mitigation strategy (REMS). We have determined that, at this time, a REMS is
`not necessary for Ozempic (semaglutide) injection to ensure that its benefits outweigh its risks.
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`Reference ID: 4190425
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`

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`NDA 209637
`Page 6
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`We will notify you if we become aware of new safety information and make a determination that
`a REMS is necessary.
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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, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert,
`Medication Guide, and patient PI (as applicable) to:
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/
`UCM443702.pdf ).
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. Form FDA 2253 is available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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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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`Reference ID: 4190425
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`

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`NDA 209637
`Page 7
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`MEDWATCH-TO-MANUFACTURER PROGRAM
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`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse
`event reports that are received directly by the FDA. New molecular entities and important new
`biologics qualify for inclusion for three years after approval. Your firm is eligible to receive
`copies of reports for this product. To participate in the program, please see the enrollment
`instructions and program description details at
`http://www.fda.gov/Safety/MedWatch/HowToReport/ucm166910.htm.
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`POST APPROVAL FEEDBACK MEETING
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`New molecular entities and new biologics qualify for a post approval feedback meeting. Such
`meetings are used to discuss the quality of the application and to evaluate the communication
`process during drug development and marketing application review. The purpose is to learn
`from successful aspects of the review process and to identify areas that could benefit from
`improvement. If you would like to have such a meeting with us, call the Regulatory Project
`Manager for this application. If you have any questions, call Peter Franks, Regulatory Project
`Manager, at 240 402-4197.
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`
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`Enclosures:
`Content of Labeling
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`Prescribing Information
` Medication Guide
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`Instructions for Use
`Carton and Container Labeling
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`Reference ID: 4190425
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`Sincerely,
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`{See appended electronic signature page}
`
`Mary T. Thanh Hai, M.D.
`Deputy Director
`Office of Drug Evaluation II
`Office of New Drugs
`Center for Drug Evaluation and Research
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`

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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 T THANH HAI
`12/05/2017
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`Reference ID: 4190425
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`