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` NDA APPROVAL
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`Boehringer Ingelheim Pharmaceuticals, Inc.
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`Attention: Chung Lee-Sogaard, Ph.D.
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`Associate Director, Regulatory Affairs, BIPI
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`900 Ridgebury Road
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`P.O. Box 368
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`Ridgefield, CT 06877
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`Dear Dr. Lee-Sogaard:
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`Please refer to your New Drug Application (NDA) dated January 29, 2014, received
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`January 30, 2014, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
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`(FDCA), for Glyxambi (empagliflozin and linagliptin) tablets; 10 mg/5 mg and 25 mg/5 mg.
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`We acknowledge receipt of your amendments dated February 24, March 6 and 13, April 14, May
`7 and 28, June 3, 9, 17, 24, and 30, July 16 and 31, August 29, September 17, October 2,
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`November 3, 2014, and January 29, 2015.
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`This new drug application provides for the use of Glyxambi (empagliflozin and linagliptin)
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`tablets as an adjunct to diet and exercise to improve glycemic control in adults with type 2
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`diabetes mellitus when treatment with both empagliflozin and linagliptin is appropriate.
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`We have completed our review of this application, as amended. It is approved, effective on the
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`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
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`WAIVER OF HIGHLIGHTS SECTION
`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
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`prescribing information. This waiver applies to all future supplements containing revised
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`labeling unless we notify you otherwise.
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`Food and Drug Administration
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` Silver Spring MD 20993
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 206073
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`Reference ID: 3694657
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` NDA 206073
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` Page 2
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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, Medication
`Guide). Information on submitting SPL files using eLIST may be found in the guidance for
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`industry SPL Standard for Content of Labeling Technical Qs and As, available at
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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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
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`carton and immediate container labels as soon as they are available, but no more than 30 days
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`after they are printed. Please submit these labels electronically according to the guidance for
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`industry Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical
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`Product Applications and Related Submissions Using the eCTD Specifications (June 2008).
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`Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on
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`heavy-weight paper or similar material. For administrative purposes, designate this submission
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`“Final Printed Carton and Container Labels for approved NDA 206073.” Approval of this
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`submission by FDA is not required before the labeling is used.
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`Marketing the product with FPL that is not identical to the approved labeling text may render the
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`product misbranded and an unapproved new drug.
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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 application because studies are
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`impossible or highly impractical and this product does not represent a meaningful therapeutic
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`benefit over existing therapies for pediatric patients and is not likely to be used in a substantial
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`number of pediatric patients. This determination was made based on the following:
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`Appropriate studies to support the safety and effectiveness of this fixed dose combination
`product would require enrollment of patients for who require treatment with three or more
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`antidiabetic agents. The population of patients appropriate for such a study are small (estimated
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`to be 1% of the pediatric type 2 diabetes mellitus population) and are impractical. Additionally,
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`Reference ID: 3694657
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` NDA 206073
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` Page 3
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` the fixed dose combination product does not provide any meaningful therapeutic benefit over the
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` use of the separate individual products.
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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, in triplicate, a cover letter requesting advisory comments, the
` proposed materials in draft or mock-up form with annotated references, and the package insert
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` to:
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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
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
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`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
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`2253. Form FDA 2253 is available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
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`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
`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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`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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`PDUFA V APPLICANT INTERVIEW
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`FDA has contracted with Eastern Research Group, Inc. (ERG) to conduct an independent interim
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`and final assessment of the Program for Enhanced Review Transparency and Communication for
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`NME NDAs and Original BLAs under PDUFA V (‘the Program’). The PDUFA V Commitment
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`Letter states that these assessments will include interviews with applicants following FDA action
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`on applications reviewed in the Program. For this purpose, first-cycle actions include approvals,
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`complete responses, and withdrawals after filing. The purpose of the interview is to better
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`understand applicant experiences with the Program and its ability to improve transparency and
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`communication during FDA review.
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`ERG will contact you to schedule a PDUFA V applicant interview and provide specifics about
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`the interview process. Your responses during the interview will be confidential with respect to
`the FDA review team. ERG has signed a non-disclosure agreement and will not disclose any
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`identifying information to anyone outside their project team. They will report only anonymized
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`results and findings in the interim and final assessments. Members of the FDA review team will
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`Reference ID: 3694657
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` NDA 206073
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` Page 4
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` be interviewed by ERG separately. While your participation in the interview is voluntary, your
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` feedback will be helpful to these assessments.
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`If you have any questions, call Callie Cappel-Lynch, Regulatory Project Manager, at
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`(301) 796-8436.
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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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`Enclosures:
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`Content of Labeling
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`PI
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`Medication Guide
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`Carton and Container Labeling
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`Reference ID: 3694657
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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
`01/30/2015
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`Reference ID: 3694657
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