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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 22334/S-40
`NDA 203985/S-13
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Novartis Pharmaceuticals Corporation
`Attention: Yanina Katz, PharmD
`Director, Regulatory Affairs
`One Health Plaza
`East Hanover, NJ 07936
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`Dear Dr. Katz:
`
`Please refer to your supplemental New Drug Applications (sNDAs) dated March 10, 2017,
`received March 10, 2017, and your amendments, submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act (FDCA), for AFINITOR (everolimus) tablets and AFINITOR
`DISPERZ (everolimus tables for oral suspension).
`
`We acknowledge receipt of your major amendment dated November 17, 2017, which extended
`the goal date by three months.
`
`The Prior Approval supplemental new drug application for NDA 203985/S-13 provides for a
`new indication for AFINITOR DISPERZ for the adjunctive treatment of adult and pediatric
`patients age 2 years and older with tuberous sclerosis complex (TSC)-associated partial-onset
`seizures. In addition, the WARNINGS AND PRECAUTIONS, Infections (5.2) subsection was
`updated to provide information on the incidence of serious infections in patients < 6 years of age
`and the USE IN SPECIFIC POPULATIONS, Pediatric Use (8.4) subsection was updated to
`describe safety and efficacy in pediatric patients in the indicated population.
`
`The Prior Approval supplemental new drug application for NDA 22334/S-40 revises the
`WARNINGS AND PRECAUTIONS, Infections (5.2) subsection to provide information on the
`incidence of serious infections in patients < 6 years of age and revises the USE IN SPECIFIC
`POPULATIONS, Pediatric Use (8.4) subsection to describe safety and efficacy in pediatric
`patients with TSC-associated partial-onset seizures.
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`In addition, the package insert for AFINITOR/AFINITOR DISPERZ was revised to comply with
`current regulations and guidances and for clarity, including re-organization of information in the
`DOSAGE AND ADMINISTRATION (2) section, deletion of the OVERDOSAGE (10) section,
`and moving existing information to new or alternative sections of labeling.
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`Reference ID: 4246867
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`

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`NDA 22334/S-40
`NDA 203985/S-13
`Page 2
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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
`text.
`
`WAIVER OF HIGHLIGHTS SECTION
`
`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.
`
`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, patient package
`insert, and the Instructions for Use, 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 include 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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`Reference ID: 4246867
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`

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`NDA 22334/S-40
`NDA 203985/S-13
`Page 3
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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
`UNDER SECTION 506B
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`We remind you of your postmarketing commitment:
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`PMC #3355-1:
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`Submit the clinical report and datasets once all patients have completed
`the Extension phase of Trial M2304, entitled “A Three-Arm,
`Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy
`and Safety of Two Trough-Ranges of Everolimus as Adjunctive Therapy
`in Patients with Tuberous Sclerosis Complex (TSC) Who Have
`Refractory Partial-Onset Seizures”, to provide additional data regarding
`the activity of everolimus as an anti-seizure medication in patients with
`TSC.
`
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`The timetable you submitted on March 13, 2018, states that you will conduct this study
`according to the following schedule:
`
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`Final Report Submission: August 2018
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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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`
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`Reference ID: 4246867
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`

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`NDA 22334/S-40
`NDA 203985/S-13
`Page 4
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`You must submit final promotional materials and package insert(s), accompanied by a Form
`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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`If you have any questions, please call Ms. Sharon Sickafuse, Senior Regulatory Health Project
`Manager, at (301) 796-2320.
`
`
`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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`ENCLOSURE:
`Content of Labeling
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`
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`Reference ID: 4246867
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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
`04/10/2018
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`Reference ID: 4246867
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