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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 206073/S-007
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` NDA 206073/S-009
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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` Boehringer Ingelheim Pharmaceuticals, Inc.
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` Attention: Daniel T. Coleman, Ph.D.
` Sr. Associate Director, Regulatory Affairs
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` 900 Ridgebury Road; P.O. Box 368
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` Ridgefield, CT 06877
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`Dear Dr. Coleman:
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`Please refer to your Supplemental New Drug Application (sNDA), submitted under section
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`505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for the following:
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`NDA
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` Number
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` 206073
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`Supplement 007
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` This Prior Approval sNDA proposes to update the Glyxambi label with results of the
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` cardiovascular safety study 1245.25, the EMPA-REG OUTCOME trial. It also proposes to
` update the prescribing information (PI) to comply with the Pregnancy and Lactation Labeling
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` Rule (PLLR).
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`Supplement 009
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`We also refer to our letter dated October 5, 2016, notifying you, under Section 505(o)(4) of the
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`FDCA, of new safety information that we believe should be included in the labeling for DPP-4
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`inhibitor products. This information pertains to the risk of bullous pemphigoid.
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`This Prior Approval sNDA, provides for revisions to the labeling for Glyxambi, consistent with
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`our October 5, 2016, letter and the labeling comments sent to you on November 22, 2016.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
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`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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` Supplement
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` Number
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` S-007
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` S-009
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` Drug Name
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` Glyxambi (empagliflozin and
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` linagliptin) tablets
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` Received
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` Dated
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` March 4, 2016
` March 4, 2016
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` November 4, 2016 November 4, 2016
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`Reference ID: 4033068
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` NDA 206073/S-007
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` NDA 206073/S-009
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` Page 2
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`WAIVER OF HIGHLIGHTS SECTION
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
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`201.57(d)(8) regarding the length of Highlights of prescribing information.
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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
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert and Medication
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`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
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`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
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`“SPL Standard for Content of Labeling Technical Qs and As at
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
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`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 that include labeling changes
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` for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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` with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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` changes approved in this supplemental application, as well as annual reportable changes and
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` annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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` up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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` should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
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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
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`We are waiving the pediatric study requirement for this supplemental application because
`necessary studies are impossible or highly impracticable. This was determined because
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`macrovascular complications of diabetes mellitus require years to develop, and they are very rare
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`in pediatric patients with diabetes mellitus. For a meaningful study to be conducted, the
`population would require a diagnosis of type 2 diabetes mellitus AND high cardiovascular risk.
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`Reference ID: 4033068
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` NDA 206073/S-007
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` NDA 206073/S-009
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` Page 3
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` The number of pediatric patients fitting these criteria is small, and the required length of follow-
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` up would likely result in patients exceeding the pediatric age range. A clinical trial for the new
` proposed indication is therefore not feasible.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`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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`OPDP Regulatory Project Manager
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
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`For more information about submitting promotional materials in eCTD format, see the draft
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`Guidance for Industry (available at:
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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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
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`All promotional materials that include representations about your drug product must be promptly
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`revised to be consistent with the labeling changes approved in this supplement, including any
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`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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`should include prominent disclosure of the important new safety information that appears in the
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`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
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`to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or
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`electronically in eCTD format. For more information about submitting promotional materials in
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`eCTD format, see the draft Guidance for Industry (available at:
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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`Reference ID: 4033068
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`Sincerely,
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`{See appended electronic signature page}
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`Jean-Marc Guettier, M.D.
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`Director
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`Division of Metabolism and Endocrinology Products
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`Office of Drug Evaluation II
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`Center for Drug Evaluation and Research
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` NDA 206073/S-007
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` NDA 206073/S-009
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` Page 4
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` REPORTING REQUIREMENTS
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` We remind you that you must comply with reporting requirements for an approved NDA
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` (21 CFR 314.80 and 314.81).
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`If you have any questions, call Michael G. White, Ph.D., Regulatory Project Manager, at
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`(240) 402-6149.
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`ENCLOSURE:
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`Content of Labeling
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`Reference ID: 4033068
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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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`JEAN-MARC P GUETTIER
`12/23/2016
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`Reference ID: 4033068
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