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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 21880/S-034
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`Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
`REMS MODIFICATION APPROVAL
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`Celgene Corporation
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`Attention: Katerina Tsironi, MBA
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`Associate Director, Regulatory Affairs
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`400 Connell Drive, Suite 7000
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`Connell Corporate Park
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`Berkeley Heights, NJ 07922
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`Dear Ms. Tsironi:
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`Please refer to your Supplemental New Drug Application (sNDA) dated December 5, 2012,
`received December 5, 2012, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Revlimid® (lenalidomide) capsules 2.5, 5, 10, 15, 20, and 25 mg.
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`We acknowledge receipt of your amendments dated February 15 and 22, 2013; March 15, 21, 26,
`28, and 29, 2013; April 11 (2) 2013, May 9, 16, 29, and 31, 2013, and June 5, 2013 and your risk
`evaluation and mitigation strategy (REMS) assessment dated May 29, 2013.
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`This “Prior Approval” supplemental new drug application provides for a new indication for
`Revlimid® (lenalidomide) capsules in patients with Mantle Cell Lymphoma whose disease has
`relapsed or progressed after two prior therapies, one of which included bortezomib, and a
`proposed modification to the approved REMS to include this new indication. In addition, this
`supplement provides for a new dosage strength in the form of a 20 mg capsule.
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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. In addition, we have found the REMS assessment to be adequate.
`
`We remind you that your NDA is approved under the provisions of 21 CFR 314.520. Marketing
`of this drug product and related activities must adhere to the substance and procedures of the
`referenced regulations (21 CFR 314.550) until you are notified otherwise.
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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
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`Reference ID: 3319577
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`

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` NDA 21880/S-034
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`Page 2
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`of labeling must be identical to the enclosed labeling (text for the package insert and 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 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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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels that are identical to the enclosed carton and
`immediate container labels submitted on May 29, 2013 as soon as they are available, but no more
`than 30 days after they are printed.
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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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`POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
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`UNDER SECTION 506B
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`We remind you of your postmarketing commitment:
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`Reference ID: 3319577
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` NDA 21880/S-034
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`Page 3
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`PMC 2048-1
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`Continue to follow patients enrolled in trial CC-5013-MCL-001 for at
`least 4 years from the date that the last patient enrolled. Submit a report
`to the Agency describing the cumulative efficacy and safety data up to
`this 4 year time point.
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`The timetable you submitted on May 16, 2013, states that you will conduct this trial according to
`the following schedule:
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`Final Protocol Submission: completed
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`Trial Completion:
`03/2016
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`Final Report Submission:
`12/2016
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`Submit clinical protocols to your IND 60100 for this product. Submit nonclinical and chemistry,
`manufacturing, and controls protocols and all postmarketing final reports to this NDA. In
`addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a status
`summary of each commitment in your annual report to this NDA. The status summary should
`include expected summary completion and final report submission dates, any changes in plans
`since the last annual report, and, for clinical studies/trials, number of patients entered into each
`study/trial. All submissions, including supplements, relating to these postmarketing
`commitments should be prominently labeled “Postmarketing Commitment Protocol,”
`“Postmarketing Commitment Final Report,” or “Postmarketing Commitment
`Correspondence.”
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for Revlimid was originally approved on August 3, 2010, and a REMS modification
`was approved on May 9, 2012, and last modified on February 8, 2013. The REMS consists of
`elements to assure safe use, implementation system, and a timetable for submission of
`assessments of the REMS. Your proposed modification to the REMS consists of incorporating
`the new indication for Revlimid® (lenalidomide) capsules for the treatment of patients with
`mantle cell lymphoma whose disease has relapsed or progressed after two prior therapies, one of
`which included bortezomib, and to include a new 20 mg capsule.
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`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
`application with elements to assure safe use from using any element to block or delay approval
`of an application under section 505(b)(2) or (j). A violation of this provision in 505-1(f) could
`result in enforcement action.
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`Your proposed modified REMS, submitted on May 31, 2013, and appended to this letter, is
`approved.
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`The timetable for submission of assessments of the REMS will remain the same as that approved
`on August 3, 2010.
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`There are no changes to the REMS assessment plan described in our February 8, 2013 letter.
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`Reference ID: 3319577
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`Page 4
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`In addition to the assessments submitted according to the timetable included in the approved
`REMS, you must submit a REMS assessment and may propose a modification to the approved
`REMS when you submit a supplemental application for a new indication for use as described in
`section 505-1(g)(2)(A) of the FDCA.
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`If the assessment instruments and methodology for your REMS assessments are not included in
`the REMS supporting document, or if you propose changes to the submitted assessment
`instruments or methodology, you should update the REMS supporting document to include
`specific assessment instrument and methodology information at least 90 days before the
`assessments will be conducted. Updates to the REMS supporting document may be included in a
`new document that references previous REMS supporting document submissions for unchanged
`portions. Alternatively, updates may be made by modifying the complete previous REMS
`supporting document, with all changes marked and highlighted. Prominently identify the
`submission containing the assessment instruments and methodology with the following wording
`in bold capital letters at the top of the first page of the submission:
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`NDA 21880 REMS CORRESPONDENCE
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`(insert concise description of content in bold capital letters, e.g.,
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`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
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`METHODOLOGY
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`An authorized generic drug under this NDA must have an approved REMS prior to marketing.
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`Should you decide to market, sell, or distribute an authorized generic drug under this NDA,
`contact us to discuss what will be required in the authorized generic drug REMS submission.
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`Prominently identify the submission containing the REMS assessments or proposed
`modifications of the REMS with the following wording in bold capital letters at the top of the
`first page of the submission as appropriate:
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`NDA 21880 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 21880
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`PROPOSED REMS MODIFICATION
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 21880
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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`Reference ID: 3319577
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` NDA 21880/S-034
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`Page 5
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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:
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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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`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, call Theresa Carioti, Regulatory Project Manager, at (301) 796-2848.
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`Sincerely,
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`{See appended electronic signature page}
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`Ann T. Farrell, MD
`Director
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`Division of Hematology Products
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Content of Labeling
`Container Labeling
`REMS
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`Reference ID: 3319577
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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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`ANN T FARRELL
`06/05/2013
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`Reference ID: 3319577
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