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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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`Silver Spring MD 20993
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`ACCELERATED APPROVAL
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`NDA 22334/S-17
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`Novartis Pharmaceuticals Corporation
`Attention: Yanina Gutman, PharmD
`Associate Director, Drug Regulatory Affairs
`One Health Plaza
`East Hanover, NJ 07936
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`Dear Dr. Gutman:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated December 19. 2011,
`received December 19, 2011, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Afinitor (everolimus) Tablets 2.5 mg, 5 mg, 7.5 mg, and 10 mg
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`tablets.
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`We acknowledge receipt of your amendments dated February 24, March 29, and April 5, 13, 16,
`19, 23, and 24, 2012.
`
`This “Prior Approval” supplemental new drug application provides for the treatment of adults
`with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate
`surgery.
`
`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
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`
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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
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`patient package insert, Medication Guide), 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.
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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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`
`
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`Reference ID: 3122590
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`

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` NDA 22334/S-17
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`Page 2
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`The SPL will be accessible from publicly available labeling repositories.
`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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`ACCELERATED APPROVAL REQUIREMENTS
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`Products approved under the accelerated approval regulations, 21 CFR 314.510, require further
`adequate and well-controlled studies/clinical trials to verify and describe clinical benefit.
`Therefore, you are required to conduct the following:
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`PMR #1892-1
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`To complete the ongoing clinical trial CRAD001M2302 entitled “A
`Randomized, Double-blind, Placebo-controlled Study of RAD001 in the
`Treatment of Angiomyolipoma in Patients with either Tuberous Sclerosis
`Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)” to
`further verify and describe the ultimate clinical outcomes of the duration
`of objective responses, incidence of nephrectomy and of renal
`embolization four years after randomization of the last patient in the study,
`as specified in the original protocol. You will submit the final
`comprehensive clinical study report, inclusive of all data collected in the
`clinical trial, as described in ICH E3.
`
`
`The timetable you submitted on April 23, 2012, states you will conduct this trial according
`to the following schedule:
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`June 10, 2010
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`Final Protocol Submission:
`January 2015
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`Study/Trial Completion:
`Final Report Submission: August 2015
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`
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`Submit final reports to this NDA as a supplemental application. For administrative purposes, all
`submissions relating to this postmarketing requirement must be clearly designated “Subpart H
`Postmarketing Requirement.”
`
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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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`
`
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`Reference ID: 3122590
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`

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` NDA 22334/S-17
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`Page 3
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`Because your request for orphan drug designation was granted, you are exempt from this
`requirement.
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`PROMOTIONAL MATERIALS
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`As required by 21 CFR 314.550, submit all promotional materials at least 30 days before the
`intended time of initial distribution of labeling or initial publication of the advertisement. Send
`two copies of all promotional materials directly to:
`
`
`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion
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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).
`
`If you have any questions, please call Ms. Sharon Sickafuse, Senior Regulatory Health Project
`Manager, at (301) 796-2320.
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`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`Patricia Keegan, M.D.
`Director
`
`Division of Oncology Products 2
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`
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`ENCLOSURE:
`Content of Labeling
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`
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`
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`Reference ID: 3122590
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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/
`----------------------------------------------------
`
`PATRICIA KEEGAN
`04/26/2012
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`Reference ID: 3122590
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`