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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 22334/S-35
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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
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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:
`
`Please refer to your supplemental New Drug Application (sNDA) dated August 24, 2015,
`received August 24, 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 inclusion of the ultimate
`outcome based on four years of additional follow-up that confirms the clinical benefit of
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`AFINITOR for the treatment of adults with renal angiomyolipoma and tuberous sclerosis
`complex (TSC), not requiring immediate surgery, approved on April 26, 2012, under the
`provisions of 21 CFR 314.510. The INDICATIONS AND USAGE, Renal Angiomyolipoma
`with Tuberous Sclerosis Complex (TSC) subsection has been revised to remove the following
`language (italicized): The effectiveness of AFINITOR in the treatment of renal angiomyolipoma
`is based on an analysis of durable objective responses in patients treated for a median of 8.3
`months. Further follow-up of patients is required to determine long-term outcomes. In addition,
`the ADVERSE REACTIONS and CLINICAL STUDIES sections of labeling have been revised
`to include the long-term follow-up data in this population.
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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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`Reference ID: 3887777
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`NDA 22334/S-35
`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 and text for the
`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.
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`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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`We request that the labeling approved today be available on your website within 10 days of
`receipt of this letter.
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`SUBPART H FULFILLED
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`We approved NDA 22334/S-17 under the regulations at 21 CFR 314 Subpart H for accelerated
`approval of new drugs for serious or life-threatening illnesses. Approval of NDA
`22334/S-35 fulfills the below post marketing requirement (PMR #1892-1) made under 21 CFR
`314.510.
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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 responses, incidence of nephrectomy and of renal embolization four
`years after randomization of the last patient in the study, as specified in the
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`original protocol.
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`
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`Reference ID: 3887777
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`NDA 22334/S-35
`Page 3
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`We remind you that there are postmarketing requirements listed in the July 20, 2012, approval
`letter that are still open.
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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:
`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
`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: 3887777
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`NDA 22334/S-35
`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 Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3887777
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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
`02/18/2016
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`Reference ID: 3887777
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