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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 22334/S-36
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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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`Novartis Pharmaceuticals Corporation
`Attention: Rose Gao
`Director, Oncology Drug Regulatory Affairs
`One Health Plaza
`Building 315, 4th Floor
`East Hanover, NJ 07936
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`Dear Ms. Gao:
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`Please refer to your Supplemental New Drug Application (sNDA) dated August 27, 2015,
`received August 27, 2015, and your amendments, submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for AFINITOR® (everolimus) tablets, for oral
`administration.
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`This Prior Approval supplemental new drug application provides for a new indication for the
`treatment of adult patients with progressive, well-differentiated, non-functional, neuroendocrine
`tumors (NET) of gastrointestinal (GI) or lung origin with unresectable, locally advanced or
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`metastatic disease.
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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
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`text.
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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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`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 and text for the
`patient package insert, with the addition of any labeling changes in pending “Changes Being
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`Reference ID: 3893024
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`

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`NDA 22334/S-36
`Page 2
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`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
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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).
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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 this drug product for this indication has an orphan drug designation, you are exempt
`from this requirement.
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`POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
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`UNDER SECTION 506B
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`We remind you of your postmarketing commitment:
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`3031-1:
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`To submit the clinical study report and datasets for the final analysis of overall
`survival (OS) for Trial CRAD001T2302, entitled “A randomized, double-blind,
`multicenter, phase III study of everolimus (RAD001) plus best supportive care
`versus placebo plus best supportive care in the treatment of patients with
`advanced NET of GI or lung origin - RADIANT-4,” and to include the final OS
`data in the product label.
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`The timetable you submitted on January 28, 2016, states that you will conduct this trial
`according to the following schedule:
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`December 2021
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`Trial Completion:
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`Final Report Submission: December 2022
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`Reference ID: 3893024
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`

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`NDA 22334/S-36
`Page 3
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`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 commitments should be
`prominently labeled “Postmarketing Commitment Final Report,” or “Postmarketing
`Commitment Correspondence.”
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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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`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/Guidances/U
`CM443702.pdf ).
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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/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
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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: 3893024
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`

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`NDA 22334/S-36
`Page 4
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`If you have any questions, please call Ms. Sharon Sickafuse, Senior Regulatory Health Project
`Manager, at (301) 796-2320.
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`Sincerely,
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`{See appended electronic signature page}
`
`
`Patricia Keegan, M.D.
`Director
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`Division of Oncology Products 2
`Office of Oncology and Hematology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`
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`Reference ID: 3893024
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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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`PATRICIA KEEGAN
`02/26/2016
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`Reference ID: 3893024
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