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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 021880/S-041
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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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`REMS MODIFICATION
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`Celgene Corporation
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`Attention: Maricel Fong, PharmD
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`Senior Manager, Regulatory Affairs
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`400 Connell Drive, Suite 7000
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`Berkeley Heights, NJ 07922
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`Dear Dr. Fong:
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`Please refer to your Supplemental New Drug Application (sNDA) dated April 22, 2014, received
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`April 22, 2014, 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 May 19; June 11 and 20; July 15; August 21
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`and 26; September 2, 15, 23, and 29; October 13, 16, 20, 21, 24, and 28; November 5 and 11,
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`2014; January 30; and February 11, 2015; and your risk evaluation and mitigation strategy
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`(REMS) assessment dated April 22, 2014.
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`This “Prior Approval” supplemental new drug application proposes to expand the indication for
`Revlimid® (lenalidomide) to include: Revlimid® (lenalidomide) in combination with
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`dexamethasone is indicated for the treatment of patients with multiple myeloma. This
`supplement also proposes a modification to the approved Revlimid® (lenalidomide) REMS
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`materials, which are a part of the REMS.
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`APPROVAL & LABELING
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` We have completed our review of this supplemental application, as amended. It is approved,
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` 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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`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
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`labeling unless we notify you otherwise.
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`Reference ID: 3703234
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` NDA 021880/S-041
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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
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` http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling (text for the package insert and Medication
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`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
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`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
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`“SPL Standard for Content of Labeling Technical Qs and As” at
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`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
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`date(s).
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`We request that the labeling approved today be available on your website within 10 days of
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`receipt of this 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
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`Because this drug product for this indication has an orphan drug designation, you are exempt
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`from this requirement.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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` The REMS for Revlimid® (lenalidomide) was originally approved on August 3, 2010 and REMS
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` modifications were approved on May 9, 2012; February 8, 2013; June 5, 2013; November 15,
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` 2013, and the REMS was last modified on September 12, 2014. The REMS consists of elements
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`Reference ID: 3703234
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` NDA 021880/S-041
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` Page 3
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` to assure safe use, an implementation system, and a timetable for submission of assessments of
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` the REMS.
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`Your proposed modification to the REMS includes incorporating the new proposed indication for
`Revlimid® (lenalidomide) in combination with dexamethasone for the treatment of multiple
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`myeloma. The following REMS materials contain an indication statement and have been
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`modified to include the new indication:
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`1. Prescriber Guide to the Revlimid REMS Program
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`2. Revlimid Risk Evaluation and Mitigation Strategy (REMS) Program Education and
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`Safety Kit
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`3. Revlimid REMS website
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`4. Welcome Letter
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`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
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`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
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`result in enforcement action.
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`Your proposed modified REMS, submitted on October 28, 2014, and appended to this letter, is
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`approved.
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`The timetable for submission of assessments of the REMS will remain the same as that approved
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`on August 3, 2010.
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`There are no changes to the REMS assessment plan described in our November 15, 2013, letter.
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`In addition to the assessments submitted according to the timetable included in the approved
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`REMS, you must submit a REMS assessment when you submit a supplemental application for a
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`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
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`the REMS supporting document, or if you propose changes to the submitted assessment
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`instruments or methodology, you should update the REMS supporting document to include
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`specific assessment instrument and methodology information at least 90 days before the
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`assessments will be conducted. Updates to the REMS supporting document may be included in a
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`new document that references previous REMS supporting document submission(s) for
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`unchanged portions. Alternatively, updates may be made by modifying the complete previous
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`REMS supporting document, with all changes marked and highlighted. Prominently identify the
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`submission containing the assessment instruments and methodology with the following wording
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`in bold capital letters at the top of the first page of the submission:
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`NDA 021880 REMS CORRESPONDENCE
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`Reference ID: 3703234
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` NDA 021880/S-041
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` Page 4
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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
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`modifications of the REMS with the following wording in bold capital letters at the top of the
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`first page of the submission as appropriate:
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`NDA 021880 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 021880
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`PROPOSED REMS MODIFICATION
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 021880
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`REMS ASSESSMENT
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`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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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`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
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
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`Information and Instructions for completing the form can be found at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`Reference ID: 3703234
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` NDA 021880/S-041
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` Page 5
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` All promotional materials that include representations about your drug product must be promptly
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` revised to be consistent with the labeling changes approved in this supplement, including any
` new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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` should include prominent disclosure of the important new safety information that appears in the
` revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
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` to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Laura Wall, Regulatory Project Manager, at (301) 796-2237.
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`Sincerely,
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`{See appended electronic signature page}
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`Ann T. Farrell, MD
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`Director
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`Division of Hematology Products
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`Office of Hematology and Oncology Products
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`Center for Drug Evaluation and Research
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`ENCLOSURES:
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`Content of Labeling
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`REMS
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`Reference ID: 3703234
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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
`02/17/2015
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`Reference ID: 3703234
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