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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 203858/S-018
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Aegerion Pharmaceuticals
`Attention: Cathy L. Walker
`Associate Director, Regulatory Affairs
`One Main Street, Suite 800
`Cambridge, MA 02142
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`Dear Ms. Walker:
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`Please refer to your supplemental New Drug Application (sNDA) dated and received
`April 5, 2018, and your amendment, submitted under section 505(b) of the Federal Food, Drug,
`and Cosmetic Act (FDCA) for JUXTAPID (lomitapide) capsules.
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`This “Changes Being Effected” sNDA provides for proposed modifications to the approved
`JUXTAPID (lomitapide) risk evaluation and mitigation strategy (REMS).
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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.
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`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENTS
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`The REMS for JUXTAPID (lomitapide) was originally approved on December 21, 2012, and the
`most recent REMS modification was approved on January 3, 2017. The REMS consists of
`elements to assure safe use, an implementation system, and a timetable for submission of
`assessments of the REMS.
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`Your proposed modifications to the REMS consist of removal of the option of emailing
`completed Patient-Prescriber Authorization Forms (PPAFs) for protection of patient information,
`requiring patients reaching age 18 to sign a PPAF (previously signed by a parent), adding
`language on the website to clarify the order of actions for prescriber participation in the REMS,
`establishing an all-electronic process for submission of the certificate of completion of training
`and knowledge assessment, streamlining of the process for completion of the prescriber
`enrollment form (use of auto-completion of the form using prescriber information already
`submitted), addition of text to the REMS website requesting pharmacies to contact Aegerion
`before attempting to certify, updating of font colors on REMS forms to enhance readability, and
`addition of clarifying language on the Prescription Authorization Form (PAF) regarding how to
`submit a prescription.
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`Reference ID: 4272001
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`NDA 203858/S-018
`Page 2
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`In accordance with section 505-1 of the FDCA, we have determined that the REMS
`modifications are necessary to minimize burden on the healthcare delivery system of complying
`with the REMS.
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`Your proposed modified REMS, submitted on April 5, 2018, amended and appended to this
`letter, is approved.
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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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`There are no changes to the REMS assessment plan described in our January 3, 2017, letter.
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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: 4272001
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`NDA 203858/S-018
`Page 3
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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 203858 REMS 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 203858 REMS ASSESSMENT
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`or
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`or
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`NEW SUPPLEMENT FOR NDA 203858
`CHANGES BEING EFFECTED IN 30 DAYS
`PROPOSED MINOR REMS MODIFICATION
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`NEW SUPPLEMENT FOR NDA 203858
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED MAJOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 203858
`PRIOR APPROVAL SUPPLEMENT
`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABEL CHANGES
`SUBMITTED IN SUPPLEMENT XXX
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`Reference ID: 4272001
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`NDA 203858/S-018
`Page 4
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`or
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA 203858
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
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`REMS REVISIONS FOR NDA 203858
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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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`
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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, or website screenshots are only in PDF format, they may be submitted as
`such, but Word format is preferred.
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`SUBMISSION OF REMS DOCUMENT IN SPL FORMAT
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`FDA can accept the REMS document in Structured Product Labeling (SPL) format. If you
`intend to submit the REMS document in SPL format, as soon as possible, but no later than
`14 days from the date of this letter, submit the REMS document in SPL format using the FDA
`automated drug registration and listing system (eLIST).
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`For more information on submitting REMS in SPL format, please email
`REMS_Website@fda.hhs.gov.
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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, call Kati Johnson, Senior Regulatory Project Manager, at
`(301) 796-1234.
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`Sincerely,
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`{See appended electronic signature page}
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`Jennifer Rodriguez Pippins, M.D. M.P.H.
`Deputy Director for Safety
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`Reference ID: 4272001
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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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`JENNIFER R PIPPINS
`06/04/2018
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`Reference ID: 4272001
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`(b)
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