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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 021880/S-023
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Celgene Corporation
`Attention: Marion Ceruzzi, Ph.D.
`Director, Regulatory Affairs
`400 Connell Drive, Suite 7000
`Berkeley Heights, NJ 07922
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`Dear Dr. Ceruzzi:
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`Please refer to your Supplemental New Drug Application (sNDA) dated June 30, 2010, received
`July 1, 2010, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA) for REVLIMID (lenalidomide) 2.5 mg, 5 mg, 10 mg, 15 mg, 25 mg Capsules.
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`We acknowledge receipt of your amendments dated August 17, September 30, November 19,
`and 24, December 10, 16, 17, 23, and 29; January 28, March 4, April 12, 19, and 26, June 24,
`October 5, and December 9, 2011.
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`The June 24, 2011, submission constituted a complete response to our April 22, 2011, action
`letter.
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`This “Prior Approval” supplemental new drug application provides for updates to the package
`insert based upon trials CC-5013-MDS-004 “A Multi-Center, Randomized, Double-Blind,
`Placebo-Controlled, 3-Arm Study of the Efficacy and Safety of 2 Doses of Lenalidomide versus
`Placebo in Red Blood Cell (RBC) Transfusion-dependent Subjects with Low or Intermediate-1-
`risk Myelodysplastic Syndromes (MDS) Associated with a Deletion 5q[31] Cytogenetic
`Abnormality” and CC-5013-MDS-003 “A Multicenter, Single-Arm, Open-Label Study of the
`Safety and Efficacy of Lenalidomide Monotherapy in Red Blood Cell Transfusion-Dependent
`Subjects with Myelodysplastic Syndromes associated with a del (5q) Cytogenetic Abnormality.”
`Also, this supplemental new drug application provides for the addition of a 2.5 mg capsule
`dosage strength.
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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.
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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
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`Reference ID: 3061609
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` NDA 021880/S-023
`Page 2
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling, 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 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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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels that are identical to the container labels
`submitted on June 30, 2010, for the 10 mg, 15 mg, and 25 mg labels and the June 24, 2011,
`submission for the 2.5 mg label except with the revisions listed below, as soon as they are
`available, but no more than 30 days after they are printed.
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`The proposed container label for the 2.5 mg strength introduces vulnerability that can lead to
`medication errors because the established name lacks prominence and the strength statement, 2.5
`mg, is not adequately differentiated. We recommend the following:
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`1. As currently presented, placing the strength within a color block does not adequately
`distinguish this strength from the 25 mg strength. We recommend you delete the color
`block and add a box around the strength to clearly differentiate it from the 25 mg
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`strength.
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`2. Revise the presentation of the established name such that it has as much prominence
`commensurate with the proprietary name in accordance with 21 CFR 201.10(g)(2). This
`may include increasing the space between the letters within the established name and
`increasing its font size.
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`Reference ID: 3061609
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` NDA 021880/S-023
`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 that there are postmarketing requirements listed in the June 29, 2006 approval
`letter that are still open.
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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
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`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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`Reference ID: 3061609
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` NDA 021880/S-023
`Page 4
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`If you have any questions, call Amy Baird, Regulatory Project Manager, at (301) 796-4969.
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`Sincerely,
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`{See appended electronic signature page}
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`
`Edvardas Kaminskas, M.D.
`Acting Deputy Director
`Division of Hematology Products
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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`Reference ID: 3061609
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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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`EDVARDAS KAMINSKAS
`12/21/2011
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`Reference ID: 3061609
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