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`ADMINISTRATION
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` NDA 203858/S-024
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`SUPPLEMENT APPROVAL
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` Amryt Pharmaceuticals, Inc.
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` US Agent for Amryt Pharmaceutical DAC
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` Attention: Karla Werre
` Senior Manager, Regulatory Affairs
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`
` 160 Federal Street, 21st floor
` Boston, MA 02110
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`Dear Ms. Werre:
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`Please refer to your supplemental new drug application (sNDA) dated and received
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`May 4, 2022, and your amendments, submitted under section 505(b) of the Federal
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`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
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`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
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`approved effective on the date of this letter, for use as recommended in the enclosed
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`agreed-upon labeling.
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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,
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`and the most recent REMS modification was approved on February 1, 2022. The REMS
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`consists of elements to assure safe use, an implementation system, and a timetable for
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`submission of assessments of the REMS.
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`Your proposed modifications to the REMS consist of:
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`1. A revised Prescription Authorization Form (PAF) consolidated to one page
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`instead of 2 pages, so that the prescriber signature and the drug order are not
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`separated by a page break
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`2. Addition of state-specific pharmacy practice language to increase pharmacy
`usability and reduce necessity of pharmacy intervention on incoming
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`prescriptions in the PAF as follows:
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`“The prescriber shall comply with his/her state-specific prescription
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`requirements such as e-prescribing, state-specific prescription form, fax
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`language, etc., as required. Noncompliance with state-specific
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`requirements could result in pharmacy outreach to the prescriber.”
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`Reference ID: 5000381
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`NDA 203858/S-024
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`Page 2
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`3. Removal of the “scan and email” option from the PAF.
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`4. Updated the Juxtapid (lomitapide) REMS website screenshots to align with
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`changes to the PAF.
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`Your proposed modified REMS, submitted on May 4, 2022, amended and appended to
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`this letter, is approved.
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`The timetable for submission of assessments of the REMS remains the same as that
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`approved on February 1, 2022.
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`There are no changes to the REMS assessment plan described in our
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`February 1, 2022, 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
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`proposed REMS modification for the addition, modification, or removal of any goal or
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`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
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`supplemental application for a new indication for use, as described in section 505-
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`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
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`indication;
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`b) A determination of the implications of a change in the benefit-risk profile for the
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`current REMS;
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`c) If the new indication for use introduces unexpected risks: A description of those
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`risks and an evaluation of whether those risks can be appropriately managed
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`with the currently approved REMS.
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`d) If a REMS assessment was submitted in the 18 months prior to submission of the
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`supplemental application for a new indication for use: A statement about whether
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`the REMS was meeting its goals at the time of that last assessment and if any
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`modifications of the REMS have been proposed since that assessment.
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`e) If a REMS assessment has not been submitted in the 18 months prior to
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`submission of the supplemental application for a new indication for use: Provision
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`of as many of the currently listed assessment plan items as is feasible.
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5000381
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`NDA 203858/S-024
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`Page 3
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`f)
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`If you propose a REMS modification based on a change in the benefit-risk profile
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`or because of the new indication of use, submit an adequate rationale to support
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`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
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`REMS was required, on patient access to the drug, and/or on the burden on the
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`health care delivery system; and other appropriate evidence or data to support
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`the proposed change. Additionally, include any changes to the assessment plan
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`necessary to assess the proposed modified REMS. If you are not proposing
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`REMS modifications, provide a rationale for why the REMS does not need to be
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`modified.
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`If the assessment instruments and methodology for your REMS assessments are not
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`included in the REMS supporting document, or if you propose changes to the submitted
`assessment instruments or methodology, you should update the REMS supporting
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`document to include specific assessment instrument and methodology information at
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`least 90 days before the assessments will be conducted. Updates to the REMS
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`supporting document may be included in a new document that references previous
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`REMS supporting document submission(s) for unchanged portions. Alternatively,
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`updates may be made by modifying the complete previous REMS supporting document,
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`with all changes marked and highlighted.
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`Prominently identify the submission containing the assessment instruments and
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`methodology with the following wording in bold capital letters at the top of the first page
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`of the submission:
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`NDA 203858 REMS ASSESSMENT METHODOLOGY
`(insert concise description of content in bold capital letters, e.g.,
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`ASSESSMENT METHODOLOGY, PROTOCOL, SURVEY METHODOLOGIES,
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`AUDIT PLAN, DRUG USE STUDY)
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`An authorized generic drug under this NDA must have an approved REMS prior to
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`marketing. Should you decide to market, sell, or distribute an authorized generic drug
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`under this NDA, contact us to discuss what will be required in the authorized generic
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`drug REMS submission.
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`We remind you that section 505-1(f)(8) of FDCA prohibits holders of an approved
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`covered application with elements to assure safe use from using any element to block
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`or delay approval of an application under section 505(b)(2) or (j). A violation of this
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`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
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`the first page of the submission as appropriate:
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5000381
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` NDA 203858/S-024
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` Page 4
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` NDA 203858 REMS ASSESSMENT
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` or
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`NEW SUPPLEMENT FOR NDA 203858/S-000
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`CHANGES BEING EFFECTED IN 30 DAYS
`PROPOSED MINOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 203858/S-000
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`PRIOR APPROVAL SUPPLEMENT
`PROPOSED MAJOR REMS MODIFICATION
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`or
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`NEW SUPPLEMENT FOR NDA 203858/S-000
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`PRIOR APPROVAL SUPPLEMENT
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`PROPOSED REMS MODIFICATIONS DUE TO SAFETY LABELING
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`CHANGES SUBMITTED IN SUPPLEMENT XXX
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`or
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 203858/S-000
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`REMS ASSESSMENT
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`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
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`containing the REMS revisions with the following wording in bold capital letters at the
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`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
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`modified REMS and other REMS-related materials in Microsoft Word format. If certain
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`documents, such as enrollment forms, or website screenshots are only in PDF format,
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`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
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`you intend to submit the REMS document in SPL format, as soon as possible, but no
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`later than 14 days from the date of this letter, submit the REMS document in SPL format
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`using the FDA automated drug registration and listing system (eLIST).
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5000381
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` NDA 203858/S-024
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` Page 5
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` For more information on submitting REMS in SPL format, please email
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` FDAREMSwebsite@fda.hhs.gov.
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` PATENT LISTING REQUIREMENTS
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`Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
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`submitted in a supplement require you to submit patent information for listing in the
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`Orange Book upon approval of the supplement. You must submit the patent information
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`required by 21 CFR 314.53(d)(2)(i)(A) through (C) and 314.53(d)(2)(ii)(A) and (C), as
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`applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
`supplement for the patent information to be timely filed (see 21 CFR
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`314.53(c)(2)(ii)). You also must ensure that any changes to your approved NDA that
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`require the submission of a request to remove patent information from the Orange Book
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`are submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
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`314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
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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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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5000381
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`

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`NDA 203858/S-024
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`Page 6
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`If you have any questions, call Ron Picking, Regulatory Project Manager, at
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`240-402-3211.
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`Sincerely,
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`{See appended electronic signature page}
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`
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`Monika Houstoun, Pharm.D., M.P.H.
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`Deputy Director for Safety
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`Division of Diabetes, Lipid Disorders, and Obesity
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`Office of Cardiology, Hematology, Endocrinology,
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`and Nephrology
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`Office of New Drugs
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`Center for Drug Evaluation and Research
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`ENCLOSURES:
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`Juxtapid REMS Document
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`Juxtapid REMS Materials:
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`• Prescriber Enrollment Form
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`• Patient Guide
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`• Prescriber-Patient Acknowledgement Form
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`• Prescription Authorization Form
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`• Pharmacy Enrollment Form
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`• Prescriber Training Module and Knowledge Assessment
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`• Pharmacy Training Module and Knowledge Assessment
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`• Fact Sheet
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`• Website Screenshots
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 5000381
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`

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`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`MONIKA A HOUSTOUN
`06/16/2022 03:53:25 PM
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`Reference ID: 5000381
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`