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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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` Silver Spring MD 20993
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` NDA 021880/S-035
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` SUPPLEMENT APPROVAL
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` REMS ASSESSMENT ACKNOWLEDGMENT
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`REMS ASSESSMENT PLAN REVISION
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`Celgene Corporation
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`Attention: Marion Ceruzzi, PhD
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`Senior Director, Regulatory Affairs
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`400 Connell Drive, Suite 7000
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`Connell Corporate Park
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`Berkley Heights, NJ 07922
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`Dear Dr. Ceruzzi:
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`Please refer to your Supplemental New Drug Application (sNDA) dated May 17, 2013, received
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`May 17, 2013, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
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`(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 June 19, July 22, September 16,
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`October 30, 2013, and your risk evaluation and mitigation strategy (REMS) assessment dated
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`August 2, 2013. We have found the REMS assessment to be complete.
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`This “Prior Approval” supplemental new drug application (S-035) provides for proposed
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`modifications to the REMS to continue the harmonization of the REMS for Thalomid®
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`(thalidomide), Revlimid® (lenalidomide), and Pomalyst® (pomalidomide) capsules, that began
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`with the February 8, 2013 approval of the REMS modifications for Revlimid® (lenalidomide)
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`and Thalomid® (thalidomide) capsules, and the approval of the REMS for Pomalyst®
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`(pomalidomide) capsules.
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`APPROVAL
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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. Your proposed modified REMS, submitted on
` October 30, 2013, and appended to this letter, is approved.
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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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`Reference ID: 3408088
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` NDA 021880/S-035
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` Page 2
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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 none of these criteria apply to your application, you are exempt from this requirement.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for Revlimid® (lenalidomide) capsules was originally approved on August 3, 2010,
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`and REMS modifications were approved on May 9, 2012, February 8, 2013, and last modified on
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`June 5, 2013. The REMS consists of elements to assure safe use, implementation system, and a
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`timetable for submission of assessments of the REMS. Your proposed modifications to the
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`REMS consist of the addition and implementation of a pharmacy portal to facilitate pharmacy
`activity within the REMS, and to harmonize the REMS with the Thalomid® (thalidomide)
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`capsules and Pomalyst® (pomalidomide) capsules REMS. In addition, the REMS assessment
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`plan will now include implementation of a survey of contraceptive use in females of reproductive
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`potential and a survey of knowledge for pharmacists.
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`Your proposed modified REMS, submitted on October 30, 2013, 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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`Our February 8, 2013 REMS modification approval letter described the REMS assessment plan.
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`The REMS assessment plan should be revised to include the results from the new Pharmacist
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`Risk Assessment Survey Protocol of pharmacist understanding of the serious risks and safe-use
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`conditions, and the results from the Adult Female of Reproductive Potential (AFRP)
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`Contraception Choice Survey Protocol regarding contraceptive use.
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`The revised REMS assessment plan should include, but is not limited to, the following:
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`1. Pregnancies:
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`a. Number of pregnancies reported during the REMS assessment reporting period and
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`annually for each REMS reporting period
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`b. Outcome of each pregnancy
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`c. Follow-up of outstanding pregnancy reports from previous assessment reporting
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`period
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`d. Root cause analysis of each reported pregnancy
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`e. Link to most recent Periodic Safety Update Report (PSUR) or Periodic Benefit-Risk
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`Evaluation Report (PBRER) that provides information on worldwide pregnancies.
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`Discussion of any new information provided in the PSUR or PBRER regarding
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`pregnancy
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`Reference ID: 3408088
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` NDA 021880/S-035
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` Page 3
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` 2. Reporting on the restricted distribution program:
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` a. The number of pharmacies and physicians certified, and patients enrolled during
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` the current REMS assessment reporting period and during each previous REMS
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`assessment reporting period
` b. Patient demographics for the current REMS assessment reporting period and for
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` previous REMS assessment reporting periods to include gender, age, diagnosis,
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` females of reproductive potential (FRP)
` c. Number of female patients for whom pregnancy testing can be discontinued
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` because menopause has been documented by follicle-stimulating
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` reporting period and for previous REMS assessment reporting periods
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` 3. Documentation of safe use conditions
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` Based on information collected through patient enrollment and mandatory surveys that are
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` used to document safe use conditions, provide information on:
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` a. Flagged prescriptions/documentations of safe use of particular interest include
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` those that have the potential of allowing pregnant patients access to the drug, and
` those that result in a delay or interruption of treatment. Provide the following,
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` relative to flagged prescriptions/documentation of safe use:
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` i. A summary of identified flags, the reasons for the flags, and the actions
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` taken to correct. Provide for the reporting period; and summarize findings
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` from each previous assessment report.
` ii. The number and proportion of flagged prescriptions intended for an FRP
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` due to lack of documentation of a negative pregnancy test, positive
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` pregnancy test, and/or a delay in obtaining a pregnancy test.
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` iii. The number and proportion of flags that caused a delay in treatment
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` initiation or a gap in therapy for patients. The time to resolution of flags
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` (mean, minimum, maximum) and include a graph of time to resolution
` versus numbers of prescriptions (or number of mandatory surveys
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` conducted to document safe use conditions) for the reporting period and
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`4. Results of pharmacist survey of knowledge regarding the serious risks and safe-use
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` conditions.
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`5. Using patient survey data, documentation of choice of contraception (information from
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`patients of method/use), and of changes to methods used (numbers of FRP using method at
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`entry and ongoing): numbers/proportions using highly effective form of birth control;
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`number/proportions using other less effective forms of birth control.
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`Reference ID: 3408088
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` NDA 021880/S-035
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` Page 4
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` The requirements for assessments of an approved REMS under section 505-1(g)(3) include, with
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` respect to each goal included in the strategy, an assessment of the extent to which the approved
` strategy, including each element of the strategy, is meeting the goal or whether one or more such
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` goals or such elements should be modified.
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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
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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
` 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
` 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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`(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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`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
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`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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`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,
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`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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`Reference ID: 3408088
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` NDA 021880/S-035
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` Page 5
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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
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`(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
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`promotional materials to the Office of Prescription Drug Promotion (OPDP), see
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`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
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`(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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`Robert C. Kane, MD
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`Deputy Director of Safety
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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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`ENCLOSURE:
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`REMS
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`Reference ID: 3408088
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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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`ROBERT C KANE
`11/15/2013
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`Reference ID: 3408088
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