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`
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`
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`-
`
`ADMINISTRAT I ON
`
`
` NDA 209803/S-004
`
` NDA 209805/S-008
`
` NDA 209806/S-006
`
`
`
` SUPPLEMENT APPROVAL
`
`
`FULFILLMENT OF POSTMARKETING
`
` REQUIREMENT
`
`
`
`
`
`
`
`
`Supplement
`
` Number
`
` 4
`
`
`
` Product Name
`
`
`
` Receipt Date
`
`
`
`
`
` Steglatro (ertugliflozin) tablets
`
` Merck Sharp & Dohme Corp
`
` Attention: Wendy L. Carofano, PharmD, RPh, PMP
`
` Director, Global Regulatory Affairs
`
` 126 E. Lincoln Avenue,
`
` P.O. Box 2000
` Mail Drop: RY34-B188
`
` Rahway, NJ 07065
`
` Dear Dr. Carofano:
`
` Please refer to your supplemental new drug applications (sNDAs), and your
`
`
`
`
` amendments, submitted under section 505(b) and pursuant to section 505(b)(2) of the
` Federal Food, Drug, and Cosmetic Act (FDCA) for the following:
`
`
`
`NDA
` Number
`
`
` 209803
`
`
`
`
`
` November 17, 2020
`
`
`
` 209805
`
`
`
` 8
`
`
`
` 209806
`
`
`
` 6
`
`
`
` Steglujan (ertugliflozin and sitagliptin)
`
` tablets
` Segluromet (ertugliflozin and
`
`
` metformin hydrochloride) tablets
`
`
`
`
`
` November 17, 2020
`
`
`
` November 17, 2020
`
`
` These Prior Approval sNDAs provide for updates to the prescribing information (PI) for
`
`
`
`
`
` each product based on the results of study MK-8835-004/B1521021, entitled
` “Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess
`
`
`
` Cardiovascular Outcomes following Treatment with Ertugliflozin (MK-8835/PF-
` 04971729) in Subjects with Type 2 Diabetes Mellitus and Established Vascular Disease,
`
`
`the VERTIS CV Study.” Updates were also made to the medication guide (MG) for each
`
`
`
` product to align with the PI.
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4858989
`
`(b) (4)
`
`

`

`
`
`
` NDA 209803/S-004
`
` NDA 209805/S-008
`
` NDA 209806/S-006
`
` Page 2
`
`
` APPROVAL & LABELING
`
` We have completed our review of these applications, as amended. They are approved,
`
`
`effective on the date of this letter, for use as recommended in the enclosed agreed-
`
` upon labeling with minor editorial revision listed below reflected in the enclosed labeling.
`
`
`
`
`
`
`• Removal of the vertical line to the left of the second paragraph in Section 5.2,
`
`
`
`
` Ketoacidosis, in the Steglujan PI
`
`
`
`
`
`
`
`
`
`We note that your September 16, 2021, submission includes final printed labeling (FPL)
`
` for your Prescribing Information and Medication Guide. We have not reviewed this FPL.
` You are responsible for assuring that the wording in this FPL is identical to that of the
`
`
` approved content of labeling in the structured product labeling (SPL) format.
`
` WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
`
` 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.
`
` 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
`
` FDA.gov.1 Content of labeling must be identical to 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.
`
` 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.2
`
` The SPL will be accessible from publicly available labeling repositories.
`
`Also within 14 days, amend all pending supplemental applications that include labeling
`changes 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 Microsoft Word
`format, that includes the changes approved in this supplemental application, as well as
`
`
`
`
`
`
`
` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`
`
` 2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`
`
` Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`
`
` U.S. Food and Drug Administration
`
` Silver Spring, MD 20993
`
` www.fda.gov
`
`
`
`
`
`Reference ID: 4858989
`
`

`

`
`
`
`
`
`
`
`
`
` NDA 209803/S-004
`
` NDA 209805/S-008
`
` NDA 209806/S-006
`
` Page 3
`
`
`annual reportable changes. To facilitate review of your submission(s), 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).
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
` 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.
`
`Because none of these criteria apply to your application, you are exempt from this
`
` requirement.
`
`
` FULFILLMENT OF POSTMARKETING REQUIREMENT
`
` The supplemental application for NDA 209803 contained the final report for the
`
` following postmarketing requirement listed in the December 19, 2017, approval letter for
`
` NDA 209803.
`
`
`
`
`
`
`
`
` PMR 3311-2 Conduct a randomized, double blind, placebo-controlled trial
`
`evaluating the effect of ertugliflozin on the incidence of major adverse
`cardiovascular events (MACE) in subjects with type 2 diabetes
`
` mellitus. The primary objective of the trial should be to demonstrate
`that the upper bound of the 2-sided 95% confidence interval for the
`
` estimated risk ratio comparing the incidence of MACE (non-fatal
`
` myocardial infarction, non-fatal stroke, cardiovascular death)
` observed with ertugliflozin to that observed in the placebo group is
`
`less than 1.3. This trial must also assess pregnancy outcomes and
`the following adverse events: amputations, ketoacidosis, complicated
`genital infections, complicated urinary tract infections, fractures,
`pancreatitis, serious hypersensitivity events, and malignancies. The
`estimated glomerular filtration rate (eGFR) should also be monitored
`
` over time to assess effects on renal function.
`
`
`We have reviewed your submission and conclude that the above requirement was
`
` fulfilled.
`
`
`
`
` U.S. Food and Drug Administration
`
` Silver Spring, MD 20993
`
` www.fda.gov
`
`Reference ID: 4858989
`
`

`

`
`
`
`
`
`
`
` NDA 209803/S-004
`
` NDA 209805/S-008
`
` NDA 209806/S-006
`
` Page 4
`
`
` We remind you that there is a postmarketing requirement listed in the December 19,
`
`
`
`
`
`
`
`
` 2017, approval letter for NDAs 209803 and 209806 that is still open.
`
` PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information about submitting promotional materials, see the
`
`
` final guidance for industry Providing Regulatory Submissions in Electronic and Non-
`Electronic Format-Promotional Labeling and Advertising Materials for Human
`Prescription Drugs. 3
`
`
`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 FDA.gov.4 Information and
`
`
` Instructions for completing the form can be found at FDA.gov.5
`
`
`
`
` REPORTING REQUIREMENTS
`
` We remind you that you must comply with reporting requirements for an approved NDA
`
`
` (21 CFR 314.80 and 314.81).
`
` If you have any questions, call Shiva Salartash, Regulatory Project Manager, at
`
` 301-837-7568.
`
`
`
`
`
`
`
`
`
`
`
` Sincerely,
`
` {See appended electronic signature page}
`
` Patrick Archdeacon, M.D.
`
` Associate Director for Therapeutics
`
`
` Division of Diabetes, Lipid Disorders, and Obesity
`
` Office of Cardiology, Hematology, Endocrinology,
`
` and Nephrology
` Center for Drug Evaluation and Research
`
`
`
`
` ENCLOSURES:
`
`o Prescribing Information
`
`
`o Medication Guide
`
`
`
`
`
` 3 For the most recent version of a guidance, check the FDA guidance web page at
` https://www.fda.gov/media/128163/download.
`
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`
`
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`
`
`
` U.S. Food and Drug Administration
`
` Silver Spring, MD 20993
`
` www.fda.gov
`
`Reference ID: 4858989
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`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.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`PATRICK ARCHDEACON
`09/17/2021 03:05:21 PM
`
`Reference ID: 4858989
`
`