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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 203441-S10
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Shire-NPS Pharmaceuticals, Inc.
`Attention: Linda Mota
`Associate Director
`Global Regulatory Affairs
`300 Shire Way
`Lexington, MA 02421
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`Dear Ms. Mota:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received on
`September 15, 2016, and your amendments, submitted under section 505(b) of the Federal Food,
`Drug, and Cosmetic Act (FDCA) for GATTEX (teduglutide [rDNA origin]), reconstituted
`lyophilized powder for subcutaneous injection, 5 mg.
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`This supplemental application proposes the following modification to the approved risk
`evaluation and mitigation strategy (REMS) for GATTEX: Removal of the communication plan
`as an element of the REMS and placement of the Dear Healthcare Professional Letters issued to
`prescribers who are identified as untrained at 60 days from the date of their initial prescription,
`and again at 12 and 24 months from the date of their initial prescription from communication
`plan into the elements to assure safe use (ETASU). This supplement is in response to our August
`15, 2016 REMS Modification Notification 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
`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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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for GATTEX (teduglutide [rDNA origin]) was originally approved on December 21,
`2012, and the most recent modification was approved on May 27, 2016. The REMS consists of a
`communication plan, elements to assure safe use and a timetable for submission of assessments
`of the REMS. In order to ensure the benefits of GATTEX (teduglutide [rDNA origin]) outweigh
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`Reference ID: 4072641
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`NDA 203441/S-010
`Page 2
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`its risks and to minimize burden on the healthcare delivery system of complying with the REMS,
`we determined that you were required to make the following REMS Modifications: removal of
`the communication plan as an element of the REMS, and to maintain the ongoing distribution of
`the DHCP Letters to prescribers identified as untrained as an activity under the elements to
`assure safe use.
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`Your proposed modified REMS, submitted on September 15, 2016, amended and appended to
`this letter, is approved. The modified REMS consists of elements to assure safe use, and a
`timetable for submission of assessments of the REMS.
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`The timetable for submission of assessments of the REMS remains the same as that approved on
`December 21, 2012.
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`The revised REMS assessment plan must include, but is not limited to, the following:
`1. Date(s) the Dear Healthcare Professional letter mailing(s) were sent and number of
`healthcare professionals that were sent this letter.
`a. Number of mailings returned
`b. Sources of the recipient lists
`2. Number of HCPs who completed the Post-training Knowledge Assessment Questions via
`the Shire REMS website or through mailing. It should be noted these Post-training
`Knowledge Assessment Questions are not a part of the REMS but will help to assess the
`effectiveness of the REMS training and hence are another part of the assessment plan.
`a. Demographics of prescribers (by specialty type) that completed the post-training
`knowledge assessment questions, to the extent possible
`b. Summary of the method used to complete the Post-training Knowledge Assessment
`Questions (on-line, fax/mail)
`c. Number of prescribers who completed each knowledge assessment question correctly
`and the number of prescribers who did not complete each post training knowledge
`assessment question correctly
`3. Number of prescribers identified through specialty pharmacy dispensing data to have
`dispensed a patient prescription who did not complete the Post-training Knowledge
`Assessment Questions (during the reporting period and cumulative).
`a. Number of prescribers who did not complete the Post-training Knowledge
`Assessment Questions who were contacted by Shire, and then who completed the
`Post-training Knowledge Assessment Questions
`4. KAB surveys of prescribers’ and patients’ understanding of the potential risks associated
`with use of GATTEX for Short Bowel Syndrome and their understanding of the
`recommended monitoring during treatment with GATTEX.
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`Reference ID: 4072641
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`NDA 203441/S-010
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`5. Narrative summary of adverse events of interest including the risks of acceleration of
`neoplastic growth and enhancement of colon polyp growth, gastrointestinal obstruction,
`biliary and pancreatic disorders, reporting from spontaneous sources, published literature,
`regulatory agencies, clinical studies and trials (clinical serious adverse events/SAEs) and
`solicited sources for entry into the Shire drug safety database.
`6. The requirements for assessments of an approved REMS under section 505-1(g)(3)
`include, in section 505-1(g)(3)(A), an assessment of the extent to which the elements to
`assure safe use are meeting the goal or goals to mitigate a specific serious risk listed in
`the labeling of the drug, or whether the goal or goals or such elements should be
`modified.
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`We remind you that in addition to the REMS assessments submitted according to the timetable in
`the approved REMS, you must include an adequate rationale to support a proposed REMS
`modification for the addition, modification, or removal of any goal or element of the REMS, as
`described in section 505-1(g)(4) of the FDCA.
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`We also remind you that you must submit a REMS assessment when you submit a supplemental
`application for a new indication for use as described in section 505-1(g)(2)(A) of the FDCA.
`This assessment should include:
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`a) An evaluation of how the benefit-risk profile will or will not change with the new
`indication.
`b) A determination of the implications of a change in the benefit-risk profile for the current
`REMS.
`c) If the new indication for use introduces unexpected risks: A description of those risks
`and an evaluation of whether those risks can be appropriately managed with the currently
`approved REMS.
`d) If a REMS assessment was submitted in the 18 months prior to submission of the
`supplemental application for a new indication for use: A statement about whether the
`REMS was meeting its goals at the time of that last assessment and if any modifications
`of the REMS have been proposed since that assessment.
`e) If a REMS assessment has not been submitted in the 18 months prior to submission of the
`supplemental application for a new indication for use: Provision of as many of the
`currently listed assessment plan items as is feasible.
`f) If you propose a REMS modification based on a change in the benefit-risk profile or
`because of the new indication of use, submit an adequate rationale to support the
`modification, including: Provision of the reason(s) why the proposed REMS
`modification is necessary, the potential effect on the serious risk(s) for which the REMS
`was required, on patient access to the drug, and/or on the burden on the health care
`delivery system; and other appropriate evidence or data to support the proposed change.
`Additionally, include any changes to the assessment plan necessary to assess the
`proposed modified REMS. If you are not proposing REMS modifications, provide a
`rationale for why the REMS does not need to be modified.
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`Reference ID: 4072641
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`NDA 203441/S-010
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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
`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:
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`NDA 203441 REMS CORRESPONDENCE
`(insert concise description of content in bold capital letters, e.g.,
`UPDATE TO REMS SUPPORTING DOCUMENT - ASSESSMENT
`METHODOLOGY
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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,
`contact us to discuss what will be required in the authorized generic drug REMS submission.
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`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved covered
`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
`result in enforcement action.
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`Prominently identify any 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:
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`NDA 203441 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 203441/S-000
`CHANGES BEING EFFECTED IN 30 DAYS
`PROPOSED MINOR REMS MODIFICATION
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`NEW SUPPLEMENT FOR NDA 203441/S-000
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED MAJOR REMS MODIFICATION
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`or
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`or
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`Reference ID: 4072641
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`NDA 203441/S-010
`Page 5
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`NEW SUPPLEMENT FOR NDA 203441/S-000
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
`SUBMITTED IN SUPPLEMENT XXX
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`or
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA 203441/S-000
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
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`REMS REVISIONS FOR NDA 203441
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`Should you choose to submit a REMS revision, prominently identify the submission containing
`the REMS revisions with the following wording in bold capital letters at the top of the first page
`of the submission:
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`To facilitate review of your submission, we request that you submit your proposed modified
`REMS and other REMS-related materials in Microsoft Word format. If certain documents, such
`as enrollment forms, are only in PDF format, they may be submitted as such, but the preference
`is to include as many as possible in Word format.
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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
`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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`OPDP Regulatory Project Manager
`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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`Alternatively, you may submit a request for advisory comments 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/Guidance
`s/UCM443702.pdf).
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`Reference ID: 4072641
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`NDA 203441/S-010
`Page 6
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`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/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found
`at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf.
`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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`If you have any questions, contact Benjamin Vali, Regulatory Project Manager, at (301) 796-
`4261 or by email at benjamin.vali@fda.hhs.gov.
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`Sincerely,
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`{See appended electronic signature page}
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`Joyce Korvick, M.D., M.P.H.
`Deputy Director for Safety
`Division of Gastroenterology and Inborn Errors
`Products
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`REMS
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`Reference ID: 4072641
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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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`JOYCE A KORVICK
`03/21/2017
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`Reference ID: 4072641
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