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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 22334/S-018
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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: Yanina Gutman, Pharm.D.
`Associate Director
`One Health Plaza
`East Hanover, NJ 07936-1080
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`Dear Ms. Gutman:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated August 27, 2012,
`received August 27, 2012, 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 August 27, August 28 and August 29, 2012.
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`This “Changes Being Effected” supplemental new drug application requested by FDA under 21
`CFR 314.70(c)(6)(iii)(E) to include revisions to the indication subependymal giant cell
`astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic
`intervention but are not candidates for curative surgical resection, an indication granted under
`accelerated approval on October 29, 2010 (NDA 22334/S-006) based upon data provided under
`NDA 203985 for Afinitor Disperz, approved this same date as follows:
`
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`Afinitor (everolimus) Tablet in adult and pediatric patients with tuberous sclerosis
`complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that
`requires therapeutic intervention but cannot be curatively resected.
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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 and required patient labeling.
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`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
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`Reference ID: 3181856
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`

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` NDA 22334/S-18
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`Page 2
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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
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`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). Information on submitting SPL files using eLIST may be found in the
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`guidance for industry titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible via 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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`POSTMARKETING REQUIREMENTS
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`We remind you of your postmarketing requirements and commitments as stated in the October
`29, 2010 approval 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 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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`Reference ID: 3181856
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`

`

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` NDA 22334/S-18
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`Page 3
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` PROMOTIONAL MATERIALS
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`Under 21 CFR 314.550, you are required to submit, during the application pre-approval review
`period, all promotional materials, including promotional labeling and advertisements, that you
`intend to use in the first 120 days following marketing approval (i.e., your launch campaign). If
`you have not already met this requirement, you must immediately contact the Office of
`Prescription Drug Promotion (OPDP) at (301) 796-1200. Please ask to speak to a regulatory
`project manager or the appropriate reviewer to discuss this issue.
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`As further required by 21 CFR 314.550, submit all promotional materials that you intend to use
`after the 120 days following marketing approval (i.e., your post-launch materials) at least 30
`days before the intended time of initial dissemination of labeling or initial publication of the
`advertisement. We ask that each submission include a detailed cover letter together with three
`copies each of the promotional materials, annotated references, and approved package insert
`(PI)/Medication Guide/patient PI (as applicable).
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`Send each submission directly to:
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`OPDP Regulatory Project Manager
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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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`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, call Vaishali Jarral, Regulatory Project Manager, at (301) 796-4248.
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`Sincerely,
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`{See appended electronic signature page}
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`
`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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`ENCLOSURES:
`Content of Labeling
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`Reference ID: 3181856
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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
`08/29/2012
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`Reference ID: 3181856
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`