DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`NDA 021880/S-031
`
`Celgene Corporation
`86 Morris Avenue
`Summit, New Jersey 07901
`
`Attention: Marion Ceruzzi, PhD
`Director, Regulatory Affairs
`
`Dear Dr. Ceruzzi:
`
`Food and Drug Administration
`
`
`Silver Spring MD 20993
`
`SUPPLEMENT APPROVAL
`
`Please refer to your Supplemental New Drug Application (sNDA) dated March 28, 2012,
`received March 29, 2012, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Revlimid® (lenalidomide) capsules 2.5, 5, 10, 15, and 25 mg.
`
`We acknowledge receipt of your amendments dated April 4, April 9, and May 1, 2012 and your
`risk evaluation and mitigation strategy (REMS) assessment dated August 3, 2011.
`
`This “Prior Approval” supplemental new drug application provides for updates to the Medication
`Guide to ensure consistency with the US Package Insert approved in Supplement 28. The
`proposed updates include the addition of the 2.5 mg dose, the risk of second primary
`malignancies, notification for the presence of lactose in Revlimid, and warning of the presence of
`Revlimid in human semen. Your approved Medication Guide will remain part of the REMS.
`In addition, this supplement provides for updates to the Revlimid® Patient-Physician Agreement
`form for adult male and male child regarding the statement that Revlimid® is present in human
`semen. These forms were updated and remain part of the REMS.
`
`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.
`
`CONTENT OF LABELING
`
`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 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.
`
`Reference ID: 3128570
`
`

`

`NDA 021880/S-031
`Page 2
`
`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.
`
`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).
`
`We request that the labeling approved today be available on your website within 10 days of
`receipt of this letter.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`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.
`
`Because none of these criteria apply to your application, you are exempt from this requirement.
`
`POSTMARKETING REQUIREMENTS AND COMMITMENTS SUBJECT TO
`REPORTING REQUIREMENTS UNDER SECTION 506B
`
`We remind you that there is a postmarketing requirement and a postmarketing commitment
`subject to reporting requirements under section 506B listed in the June 29, 2006 approval letter
`that are still open.
`
`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
`
`The REMS for Revlimid® (lenalidomide) capsules was originally approved on August 3, 2010.
`The REMS consists of a Medication Guide, communication plan, elements to assure safe use,
`implementation system, and a timetable for submission of assessments of the REMS. Your
`proposed modifications to the REMS consist of a revised Medication Guide to include
`information about the risk of second primary malignancies, the addition of the 2.5 mg dosage
`form, warning that Revlimid® (lenalidomide) capsules is present in human semen, and
`notification of the presence of lactose in Revlimid® (lenalidomide) capsules.
`
`Your modified REMS, submitted on May 1, 2012, and appended to this letter, is approved.
`
`Reference ID: 3128570
`
`

`

`NDA 021880/S-031
`Page 3
`
`The timetable for submission of assessments of the REMS will remain the same as that approved
`on August 3, 2010.
`
`There are no changes to the REMS assessment plan described in our August 3, 2010 letter.
`
`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 FDCA.
`
`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 submission(s) 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:
`
`NDA 021880 REMS CORRESPONDENCE
`
`(insert concise description of content in bold capital letters, e.g.,
`
`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
`
`METHODOLOGY)
`
`
`An authorized generic drug under this NDA must have an approved REMS prior to marketing.
`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.
`
`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:
`
`NDA 021880 REMS ASSESSMENT
`
`NEW SUPPLEMENT FOR NDA 021880
`PROPOSED REMS MODIFICATION
`REMS ASSESSMENT
`
`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA 021880
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
`
`If you do not submit electronically, please send 5 copies of REMS-related submissions.
`
`Reference ID: 3128570
`
`

`

`NDA 021880/S-031
`Page 4
`
`PROMOTIONAL MATERIALS
`
`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:
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`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/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.
`
`All promotional materials that include representations about your drug product must be promptly
`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
`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
`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
`
`REPORTING REQUIREMENTS
`
`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, call Theresa Ferrara, Regulatory Project Manager, at (301) 796-2848.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Robert C. Kane, M.D.
`Deputy Director for Safety (acting)
`Division of Hematology Products
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
`
`ENCLOSURE:
`Content of Labeling
`REMS
`
`Reference ID: 3128570
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ROBERT C KANE
`05/09/2012
`
`Reference ID: 3128570
`
`