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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 209805/S-004
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
`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
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`Dear Dr. Fuh:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received September
`25, 2018, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Steglujan (ertugliflozin and sitagliptin) tablets.
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`We also refer to our letter dated August 29, 2018, notifying you, under Section 505(o)(4) of the
`FDCA, of new safety information that we believe should be included in the labeling for the
`sodium-glucose cotransporter-2 (SGLT-2) inhibitors drug class, of which, Steglujan is a member.
`This information pertains to the risk of necrotizing fasciitis of the perineum (also known as
`Fournier’s gangrene).
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`This supplemental new drug application provides for revisions to the labeling for Steglujan
`consistent with our August 29, 2018, Safety Labeling Change Notification letter, and the
`comments sent to you in our October 5, 16, 17, and 18, 2018, correspondence.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text and with the minor editorial revisions listed below and indicated in the enclosed labeling.
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`• The revision dates listed in the Highlights of Prescribing Information and Medication
`Guide were updated to reflect the date of approval of this supplement.
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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
`201.57(d)(8) regarding the length of Highlights of prescribing information.
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`Reference ID: 4341187
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`NDA 209805/S-004
`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
`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 and indicated, the
`enclosed labeling (text for the prescribing information and Medication Guide) with the addition
`of any labeling changes in pending “Changes Being Effected” (CBE) 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 “SPL Standard for Content of Labeling Technical Qs and As”
`at http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/
`UCM072392.pdf.
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`The SPL will be accessible via publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications for this NDA, including CBE
`supplements for which FDA has not yet issued an action letter, with the content of labeling
`[21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes with the
`revisions indicated above approved in this supplemental application, as well as annual reportable
`changes, and annotate each change. To facilitate review of your submission, provide a
`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft Word
`version. The marked-up copy 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
`active ingredients (which includes new salts and new fixed combinations), 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 in pediatric
`patients unless this requirement is waived, deferred, or inapplicable.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`Reference ID: 4341187
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`NDA 209805/S-004
`Page 3
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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 the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the prescribing information to:
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`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/Guidance
`s/UCM443702.pdf ).
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`You must submit final promotional materials and prescribing information, accompanied by a
`Form FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)].
`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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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or
`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/Guidance
`s/UCM443702.pdf ).
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`Reference ID: 4341187
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`NDA 209805/S-004
`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
`(21 CFR 314.80 and 314.81). We also request that you submit all reports (foreign and domestic)
`of Fournier’s gangrene, regardless of labeling status, as 15-day expedited safety reports for a
`period of ten years from the date of this letter.
`If you have any questions, call Liz Godwin, Regulatory Project Manager, at 240-402-3438.
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`Sincerely,
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`{See appended electronic signature page}
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`William Chong, M.D.
`Director (Acting)
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Content of Labeling
`Prescribing Information
`Medication Guide
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`Reference ID: 4341187
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`Signature Page 1 of 1
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`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
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`/s/
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`WILLIAM H CHONG
`10/26/2018
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`Reference ID: 4341187
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`(b
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