CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`APPLICATION NUMBER:
`
` 209805Orig1s000
`
` Steglujan tablets, 5 mg/100 mg and 15 mg/100 mg
`
`ertugliflozin and sitagliptin
`
`
`
`Trade Name:
`
`Generic or Proper
`Name:
`
`Sponsor:
`
`
`
`
`Approval Date:
`
`
`Indication:
`
`
`Merck Sharp & Dohme Corp.
`
`December 19, 2017
`
`For the use of Steglujan (ertugliflozin and sitagliptin)
`tablets as an adjunct to diet and exercise to improve
`glycemic control in adults with type 2 diabetes mellitus
`when treatment with both ertugliflozin and sitagliptin is
`appropriate.
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`209805Orig1s000
`
`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
`Clinical Review(s)
`Product Quality Review(s)
`Non-Clinical Review(s)
`Statistical Review(s)
`Clinical Microbiology / Virology Review(s)
`Clinical Pharmacology Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
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`X
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`X
`X
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`X
`X
`X
`X
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`X
`X
`X
`X
`X
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`

`

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`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`209805Orig1s000
`
`
`APPROVAL LETTER
`
`

`

`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`NDA 209805
`
`Merck Sharp & Dohme Corp.
`Attention: Vivian Fuh, M.D., F.A.C.P.
`Executive Director, Global Regulatory Affairs
`126 E. Lincoln Avenue, P.O. Box 2000
`Mail Drop: RY34-B188
`Rahway, NJ 07065
`
`Dear Dr. Fuh:
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`NDA APPROVAL
`
`Please refer to your New Drug Application (NDA) dated and received December 19, 2016, and
`your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA) for Steglujan (ertugliflozin and sitagliptin) tablets, 5 mg/100 mg and 15 mg/100 mg.
`
`This new drug application provides for the use of Steglujan (ertugliflozin and sitagliptin) tablets
`as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
`mellitus when treatment with both ertugliflozin and sitagliptin 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 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.
`
`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, except with the revisions listed, the enclosed labeling
`(text for the prescribing information and 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
`/UCM072392.pdf.
`
`Reference ID: 4197661
`
`

`

`NDA 209805
`Page 2
`
`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 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 209805.” Approval of this submission by
`FDA is not required before the labeling is used.
`
`ADVISORY COMMITTEE
`
`Your application for Steglujan (ertugliflozin and sitagliptin) was not referred to an FDA advisory
`committee because this drug is not the first in its class.
`
`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 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.
`
`We are waiving the pediatric study requirement for ages 10 through 17 years (inclusive) because
`this product does not represent a meaningful therapeutic benefit over existing therapies for
`pediatric patients in this age range and is not likely to be used in a substantial number of
`pediatric patients in this age range. 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 who require treatment with three or more
`antihyperglycemic 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, the fixed dose combination product does not provide any
`meaningful therapeutic benefit over the use of the separate individual products.
`
`Reference ID: 4197661
`
`

`

`NDA 209805
`Page 3
`
`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,
`Medication Guide, and patient PI (as applicable) to:
`
`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
`
`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/Guidan
`ces/UCM443702.pdf ).
`
`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).
`
`We request that for a period of 5 years from the U.S. approval date, you submit all cases of
`ketoacidosis reported with Steglujan (ertugliflozin and sitagliptin) tablets as 15-day Alert reports
`(as described under 21 CFR 314.80(c)(1)), and that you provide detailed analyses of events of
`ketoacidosis reported from clinical study and post-marketing reports in your periodic safety
`report (i.e., the Periodic Adverse Drug Experience Report [PADER] required under 21 CFR
`314.80(c)(2) or the ICH E2C Periodic Benefit-Risk Evaluation Report [PBRER] format). These
`analyses should show cumulative data relative to the date of approval of Steglujan (ertugliflozin
`and sitagliptin) tablets as well as relative to prior periodic safety reports. Medical literature
`reviews for case reports/case series of ketoacidosis reported with Steglujan (ertugliflozin and
`sitagliptin) tablets should also be provided in the periodic safety report.
`
`Reference ID: 4197661
`
`

`

`NDA 209805
`Page 4
`
`MEDWATCH-TO-MANUFACTURER PROGRAM
`
`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.
`
`POST APPROVAL FEEDBACK MEETING
`
`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 Liz Godwin, Regulatory Project Manager, at (240) 402-3438.
`
`Sincerely,
`
`{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
`
`Enclosures:
`Content of Labeling
`Carton and Container Labeling
`
`Reference ID: 4197661
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MARY T THANH HAI
`12/19/2017
`
`Reference ID: 4197661
`
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