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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 022334/S-014/S-015
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`Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL/
`FULFILLMENT OF POSTMARKETING
`REQUIREMENT AND COMMITMENT
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`Novartis Pharmaceuticals Corporation
`One Health Plaza
`East Hanover, NJ 07936-1080
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`Attention:
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`Dear Dr. Thomas:
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`Please refer to your Supplemental New Drug Applications (sNDAs) dated July 11 and 27, 2011,
`received July 11 and 27, 2011, respectively, submitted under section 505(b) of the Federal Food,
`Drug, and Cosmetic Act (FDCA) for Afinitor® (everolimus) tablets.
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`We acknowledge receipt of your amendments dated July 18, October 12 and November 23,
`2011.
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`“Prior Approval” supplemental new drug application 014 provides for revisions to the package
`insert reflecting the final results from protocol C2240. This supplement was submitted in
`response to the following postmarketing commitment from the March 30, 2009, approval letter:
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`610-2: Submit the final, per-protocol overall survival analysis of protocol C2240 which was to
`be conducted 2 years after randomization of the last patient.
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`Lincy Thomas, Pharm.D.
`Senior Associate Director, Drug Regulatory Affairs
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`Protocol Submission:
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`Trial Start Date:
`Final Report Submission:
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`July 27, 2006
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`December 6, 2006
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`June 2010
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`“Prior Approval” supplemental new drug application 015 provides for revisions to the package
`insert based on results from a hepatic impairment study as well as a drug-drug interaction study
`with midazolam. This supplement was submitted in response to the following postmarketing
`requirement from the March 30, 2009, approval letter:
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`Reference ID: 3109460
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` NDA 022334/S-014/S-015
`Page 2
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`610-1: Conduct a trial in patients with severe hepatic impairment (Child-Pugh Class C). This
`trial need not be conducted in patients with cancer and a single dose evaluation will be
`appropriate. The protocol should be submitted prior to initiation for review and concurrence.
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`The timetable you submitted on March 3, 2009, states that you will conduct this trial
`according to the following timetable:
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`Final Protocol Submission: May 14, 2009
`Trial Start Date:
`October 14, 2009
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`Final Report Submission:
`April 14, 2011
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`We have completed our review of these supplemental applications, as amended. They are
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling text.
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`In addition, we conclude that the above requirement and commitment were both fulfilled.
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`We remind you that there are postmarketing requirements listed in the October 29, 2010, and
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`May 5, 2011, approval letters that are still open.
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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 the enclosed labeling (text for the package insert, text for the
`patient package insert), with the addition of any labeling changes in pending “Changes Being
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`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
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`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.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 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).
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`Reference ID: 3109460
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` NDA 022334/S-014/S-015
`Page 3
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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, 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.
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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 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:
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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
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` FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on page 2 of the form. 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
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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).
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`Reference ID: 3109460
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` NDA 022334/S-014/S-015
`Page 4
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`If you have any questions, call Christy Cottrell, Regulatory Project Manager, at (301) 796-4256.
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`Sincerely,
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`{See appended electronic signature page}
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`Amna Ibrahim, M.D.
`Deputy Director
`Division of Oncology Products 1
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3109460
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`

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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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`AMNA IBRAHIM
`03/30/2012
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`Reference ID: 3109460
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`