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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 21880/S-052
`NDA 21880/S-053
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Celgene
`Attention: Lisa Suttner, MS, RAC
`Director, Regulatory Affairs
`86 Morris Ave
`Summit, NJ 07901
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`Dear Ms. Suttner:
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`Please refer to your Supplemental New Drug Applications (S-052) dated
`November 1, 2017, received November 2, 2017, (S-053) dated November 3, 2017, received
`November 3, 2017 and your amendments, 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 also refer to our letter dated October 12, 2017, notifying you, under Section 505(o)(4) of the
`FDCA, of new safety information that we believe should be included in the labeling for
`thalidomide-analogue immunomodulatory agents. This information pertains to the risk of
`increased mortality with the addition of pembrolizumab, a programmed death receptor-1 (PD-1)
`blocking monoclonal antibody, to standard multiple myeloma treatment with a thalidomide
`analogue and dexamethasone.
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`Supplemental new drug application S-052 provides for revisions to the labeling for Revlimid,
`consistent with our October 12, 2017 Safety Labeling Change Notification letter.
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`Supplemental new drug application S-053 provides for the addition of information regarding
`solid organ transplant rejection to Section 6 ADVERSE REACTIONS, subsection 6.2
`Postmarketing Experience of the Prescriber Information.
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`APPROVAL & LABELING
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`We have completed our review of these supplemental applications, as amended. They are
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling text.
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`We note that your November 29, 2017, submission includes final printed labeling (FPL) for your
`package insert, and Medication Guide. We have not reviewed this FPL. You are responsible for
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`Reference ID: 4188381
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`NDA 21880/S-052/S-053
`Page 2
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`assuring that the wording in this printed labeling is identical to that of the approved content of
`labeling in the structured product labeling (SPL) format.
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`WAIVER OF HIGHLIGHTS SECTION
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`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.
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`CONTENT OF LABELING
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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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`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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`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, by fax to 301-847-8444, or
`electronically in eCTD format. For more information about submitting promotional materials in
`eCTD format, see the draft guidance for industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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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: 4188381
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`NDA 21880/S-052/S-053
`Page 3
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`If you have any questions, call Ms. Diane Leaman, Safety Regulatory Project Manager, at
`(301) 796-1424.
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`Sincerely,
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`{See appended electronic signature page}
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`Barry W. Miller
`Deputy Director for Safety (acting)
`Division of Hematology Products
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 4188381
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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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`BARRY W MILLER
`11/30/2017
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`Reference ID: 4188381
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