Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 203415/S-003
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`Astellas Pharma US, Inc.
`Attention: Alison Hayles
`Director, Regulatory Affairs
`1 Astellas Way
`Northbrook, IL 60062
`
`Dear Ms. Hayles:
`
`
`
`Please refer to your Supplemental New Drug Application (sNDA) dated March 17, 2014,
`received March 18, 2014, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Xtandi® (enzalutamide) Capsules 40 mg.
`
`
`
`We acknowledge receipt of your amendments dated August 6, 18, and 21, 2014.
`
`This “Prior Approval” supplemental new drug application provides for a new indication for the
`treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
`
`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.
`
`
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`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, text for the
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`patient package insert), 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 titled
`“SPL Standard for Content of Labeling Technical Qs and As at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`Reference ID: 3621547
`
`AVENTIS EXHIBIT 2165
`Mylan v. Aventis, IPR2016-00712
`
`1
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`

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`NDA 203415/S-003
`Page 2
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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 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 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).
`
`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 metastatic prostate
`cancer does not occur in children.
`
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`POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
`
`UNDER SECTION 506B
`
`We remind you of your postmarketing commitment:
`
`
`
`2776-1
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`Submit an updated overall survival analysis (containing a minimum of 765 events)
`and datasets for the PREVAIL (MDV3100-03) trial. The updated analysis should
`include all patients. The submission should contain information about the use of post-
`progression therapies for metastatic castration-resistant prostate cancer that may
`prolong overall survival.
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`
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`The timetable you submitted on August 26, 2014, states that you will conduct this trial according
`to the following schedule:
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`December 2014
`Trial Completion:
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`Final Report Submission: March 2015
`
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`Submit clinical protocols to your IND 074563 for this product. Submit nonclinical and
`chemistry, manufacturing, and controls protocols and all postmarketing final reports to this
`NDA. In addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a
`status summary of each commitment in your annual report to this NDA. The status summary
`should include expected summary completion and final report submission dates, any changes in
`plans since the last annual report, and, for clinical studies/trials, number of patients entered into
`each study/trial. All submissions, including supplements, relating to these postmarketing
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`Reference ID: 3621547
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`2
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`

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`NDA 203415/S-003
`Page 3
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`commitments should be prominently labeled “Postmarketing Commitment Protocol,”
`“Postmarketing Commitment Final Report,” or “Postmarketing Commitment
`Correspondence.”
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`PROMOTIONAL MATERIALS
`
`
`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 package insert(s) to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`You must submit final promotional materials and package insert(s), 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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`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 Charlene Wheeler, Regulatory Project Manager, at
`(301) 796-1141.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`Amna Ibrahim, M.D.
`Acting Director
`Division of Oncology Products 1
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3621547
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`3
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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/
`----------------------------------------------------
`
`AMNA IBRAHIM
`09/10/2014
`
`Reference ID: 3621547
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`4