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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 202155/S-009
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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` Bristol-Myers Squibb
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` ATTENTION: Sekayi Mushonga, Pharm.D.
` Associate Director, Global Regulatory Sciences
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` P.O. Box 4000
` Princeton, NJ 08543-4000
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` Dear Dr. Mushonga:
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`Please refer to your Supplemental New Drug Application (sNDA) dated June 9, 2014, received June 9,
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`2014, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Eliquis
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`(apixaban) 2.5 and 5 mg tablets.
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`We also refer to our label supplement request and risk evaluation and mitigation strategy (REMS)
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`modification notification letter dated April 29, 2014.
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`We acknowledge receipt of your amendment dated July 25, 2014.
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`This supplemental new drug application, consistent with our April 29, 2014 letter, provides for label
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`changes so that the description of the risk of premature discontinuation of Eliquis (apixaban) is similar to
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`those in the label for the other member of the drug class, and a proposed modification to the approved
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`REMS to conform the REMS communication plan materials to the revised labeling.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended, and it is approved, effective
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`on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for Eliquis (apixaban) was originally approved on December 28, 2012. The REMS consists
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`of a communication plan and a timetable for submission of assessments of the REMS. In accordance with
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`our REMS modification letter dated April 29, 2014, your proposed modifications to the REMS consist of
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`modifications to the communication plan materials to reflect the revised labeling.
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`Your proposed modified REMS, submitted on June 9, 2014, and appended to this letter, is approved.
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`The timetable for submission of assessments of the REMS will remain the same as that approved on
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`December 28, 2012.
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`There are no changes to the REMS assessment plan described in our December 28, 2012 letter.
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`In addition to the assessments submitted according to the timetable included in the approved REMS, you
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`must submit a REMS assessment and may propose a modification to the approved REMS when you
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`Reference ID: 3608558
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` NDA 202155/S-009 Approval Letter
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` Page 2
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`submit a supplemental application for a new indication for use as described in section 505-1(g)(2)(A) of
`the FDCA.
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`If the assessment instruments and methodology for your REMS assessments are not included in the
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`REMS supporting document, or if you propose changes to the submitted assessment instruments or
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`methodology, you should update the REMS supporting document to include specific assessment
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`instrument and methodology information at least 90 days before the assessments will be conducted.
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`Updates to the REMS supporting document may be included in a new document that references previous
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`REMS supporting document submission(s) for unchanged portions. Alternatively, updates may be made
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`by modifying the complete previous REMS supporting document, with all changes marked and
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`highlighted. Prominently identify the submission containing the assessment instruments and
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`methodology with the following wording in bold capital letters at the top of the first page of the
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`submission:
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`NDA 202155 REMS CORRESPONDENCE
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`(insert concise description of content in bold capital letters, e.g.,
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`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT METHODOLOGY)
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`An authorized generic drug under this NDA must have an approved REMS prior to marketing. Should
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`you decide to market, sell, or distribute an authorized generic drug under this NDA, contact us to discuss
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`what will be required in the authorized generic drug REMS submission.
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`Prominently identify the submission containing the REMS assessments or proposed modifications of the
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`REMS with the following wording in bold capital letters at the top of the first page of the submission as
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`appropriate:
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`NDA 202155 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 202155
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`PROPOSED REMS MODIFICATION
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 202155
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`REMS ASSESSMENT
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`PROPOSED REMS MODIFICATION (if included)
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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`Reference ID: 3608558
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` NDA 202155/S-009 Approval Letter
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` Page 3
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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
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`[21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA automated drug
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`registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content of
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`labeling must be identical to the enclosed labeling (text for the package insert and Medication Guide),
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`with the addition of any labeling changes in pending “Changes Being Effected” (CBE) supplements, as
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`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
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`Standard for Content of Labeling Technical Qs and As at
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/UCM0723
`92.pdf
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that includes labeling changes for this
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`NDA, including CBE supplements for which FDA has not yet issued an action letter, with the content of
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`labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this
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`supplemental application, as well as annual reportable changes and annotate each change. To facilitate
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`review of your submission, provide a highlighted or marked-up copy that shows all changes, as well as a
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`clean Microsoft Word version. The marked-up copy should provide appropriate annotations, including
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`supplement number(s) and annual report date(s).
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`We request that the labeling approved today be available on your website within 10 days of receipt of this
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`letter.
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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
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`ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are
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`required to contain an assessment of the safety and effectiveness of the product for the claimed
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`indication(s) 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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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional labeling. To
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`do so, submit the following, in triplicate, (1) a cover letter requesting advisory comments, (2) the
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`proposed materials in draft or mock-up form with annotated references, and (3) the package insert(s) 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 (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form FDA 2253,
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`at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available
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`Reference ID: 3608558
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` NDA 202155/S-009 Approval Letter
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` Page 4
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` 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
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`information about submission of promotional materials to the Office of Prescription Drug Promotion
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`All promotional materials that include representations about your drug product must be promptly revised
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`to be consistent with the labeling changes approved in this supplement, including any new safety
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`information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials should include
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`prominent disclosure of the important new safety information that appears in the revised package
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`labeling. Within 7 days of receipt of this letter, submit your statement of intent to comply with
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`21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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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
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`and 314.81).
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`If you have any questions, please call:
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`Alison Blaus, RAC
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`Regulatory Project Manager
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`(301) 796-1138
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`Sincerely,
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`{See appended electronic signature page}
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`Mary Ross Southworth, PharmD
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`Safety Deputy Director
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`Division of Cardiovascular & Renal Products
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`Office of Drug Evaluation I
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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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`REMS
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`Reference ID: 3608558
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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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`MARY R SOUTHWORTH
`08/12/2014
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`Reference ID: 3608558
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