`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`
`APPLICATION NUMBER:
`
`206073Orig1s000
`
`
`Glyxambi
`
`January 30, 2015
`
`Trade Name:
`
`Empagliflozin; Linagliptin
`Generic Name:
`
`Sponsor:
`
`Approval Date:
`
`Indications:
`
`Boehringer Ingelheim
`
` 1) An adjunct to diet and exercise to improve
`glycemic control in adults with type 2 diabetes
`mellitus when treatment with both empagliflozin
`and linagliptin is appropriate.
`
`
`
`
`
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`206073Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology / Virology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`
`X
`
`
`X
`
`
`X
`X
`
`X
`X
`X
`X
`X
`X
`X
`X
`
`X
`
`

`

`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`206073Orig1s000
`APPROVAL LETTER
`
`
`
`
`
`
`
`

`

`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`NDA 206073
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`NDA APPROVAL
`
`
`Boehringer Ingelheim Pharmaceuticals, Inc.
`Attention: Chung Lee-Sogaard, Ph.D.
`Associate Director, Regulatory Affairs, BIPI
`900 Ridgebury Road
`P.O. Box 368
`Ridgefield, CT 06877
`
`
`Dear Dr. Lee-Sogaard:
`
`Please refer to your New Drug Application (NDA) dated January 29, 2014, received
`January 30, 2014, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA), for Glyxambi (empagliflozin and linagliptin) tablets; 10 mg/5 mg and 25 mg/5 mg.
`
`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,
`November 3, 2014, and January 29, 2015.
`
`This new drug application provides for the use of Glyxambi (empagliflozin and linagliptin)
`tablets as an adjunct to diet and exercise to improve glycemic control in adults with type 2
`diabetes mellitus when treatment with both empagliflozin and linagliptin is appropriate.
`
`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.
`
`WAIVER OF HIGHLIGHTS SECTION
`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.
`
`Reference ID: 3694657
`
`

`

`NDA 206073
`Page 2
`
`
`CONTENT OF LABELING
`
`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). 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.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`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 Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical
`Product Applications and Related Submissions Using the eCTD Specifications (June 2008).
`Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on
`heavy-weight paper or similar material. For administrative purposes, designate this submission
`“Final Printed Carton and Container Labels for approved NDA 206073.” Approval of this
`submission by FDA is not required before the labeling is used.
`
`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`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.
`
`We are waiving the pediatric study requirement for this application because studies are
`impossible or highly impractical and this product does not represent a meaningful therapeutic
`benefit over existing therapies for pediatric patients and is not likely to be used in a substantial
`number of pediatric patients. This determination was made based on the following:
`
`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
`antidiabetic agents. The population of patients appropriate for such a study are small (estimated
`to be 1% of the pediatric type 2 diabetes mellitus population) and are impractical. Additionally,
`
`Reference ID: 3694657
`
`

`

`NDA 206073
`Page 3
`
`
`the fixed dose combination product does not provide any meaningful therapeutic benefit over the
`use of the separate individual products.
`
`PROMOTIONAL MATERIALS
`
`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
`to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`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.
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`PDUFA V APPLICANT INTERVIEW
`
`FDA has contracted with Eastern Research Group, Inc. (ERG) to conduct an independent interim
`and final assessment of the Program for Enhanced Review Transparency and Communication for
`NME NDAs and Original BLAs under PDUFA V (‘the Program’). The PDUFA V Commitment
`Letter states that these assessments will include interviews with applicants following FDA action
`on applications reviewed in the Program. For this purpose, first-cycle actions include approvals,
`complete responses, and withdrawals after filing. The purpose of the interview is to better
`understand applicant experiences with the Program and its ability to improve transparency and
`communication during FDA review.
`
`ERG will contact you to schedule a PDUFA V applicant interview and provide specifics about
`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
`identifying information to anyone outside their project team. They will report only anonymized
`results and findings in the interim and final assessments. Members of the FDA review team will
`
`Reference ID: 3694657
`
`

`

`NDA 206073
`Page 4
`
`
`be interviewed by ERG separately. While your participation in the interview is voluntary, your
`feedback will be helpful to these assessments.
`
`If you have any questions, call Callie Cappel-Lynch, Regulatory Project Manager, at
`(301) 796-8436.
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Jean-Marc Guettier, M.D.
`Director
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`
`
`Enclosures:
`Content of Labeling
`
`PI
` Medication Guide
`Carton and Container Labeling
`
`Reference ID: 3694657
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`JEAN-MARC P GUETTIER
`01/30/2015
`
`Reference ID: 3694657
`
`