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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 22334/S-22
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`NDA 203985/S-3
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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 Corp.
`Attention: Lincy Thomas, PharmD, MBA
`Director, Drug Regulatory Affairs
`One Health Plaza
`East Hanover, NJ 07936
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`Dear Dr. Thomas:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated May 31, 2013, received
`May 31, 2013, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA) for AFINITOR (everolimus) tablets for oral administration; 2.5 mg, 5 mg, 7.5 mg and
`10 mg.
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`Please also refer to your Supplemental New Drug Application (sNDA) dated June 18, 2013,
`received June 18, 2013, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic
`Act (FDCA) for AFINITOR DISPERZ (everolimus tablets for oral suspension); 2 mg,
`3 mg, and 5 mg.
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`We acknowledge receipt of your amendments to NDA 22334/S-22 dated September 20, October
`15, October 18, and October 29, 2013. We also acknowledge receipt of your amendments to
`NDA 203985/S-3 dated September 23, October 14, October 18, and October 29, 2013. We also
`refer to your submission of October 17, 2012, containing a postmarketing requirement (PMR)
`final study report for Study CRAD001C2325 and to our October 12, 2013, letter stating that
`PMR 1756-2 had been fulfilled.
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`These Prior Approval” supplemental new drug applications provide for modifications of the
`INDICATIONS AND USAGE, subsection 1.2 [Advanced Neuroendocrine Tumors of Pancreatic
`Origin (PNET)] and the Patient Package Insert to state that AFINITOR is not indicated for the
`treatment of patients with functional carcinoid tumors and for modifications to the CLINICAL
`STUDIES, Advanced Neuroendocrine Tumors subsection (14.2) to include the results of the
`final analysis of overall survival from Study CRAD001C2325.
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`APPROVAL & LABELING
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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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`Reference ID: 3402565
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`NDA 22334/S-22
`NDA 203985/S-3
`Page 2
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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 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
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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 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
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`Reference ID: 3402565
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`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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`NDA 22334/S-22
`NDA 203985/S-3
`Page 3
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`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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` 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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`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 Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3402565
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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
`11/06/2013
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`Reference ID: 3402565
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