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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 203858/S-001
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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` Aegerion Pharmaceuticals, Inc.
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` Attention: Martha J. Carter
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` Chief Regulatory Officer and Senior Vice President
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` 101 Main Street, Suite 1850
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` Cambridge, MA 02142
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`Dear Ms. Carter:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received
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`February 7, 2013, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
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`(FDCA) for Juxtapid (lomitapide) capsules 5 mg, 10 mg, and 20 mg.
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`We acknowledge receipt of your amendments dated July 2 and August 5 and 7, 2013, and your
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`risk evaluation and mitigation strategy (REMS) assessment dated June 19, 2013.
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`This Prior Approval supplemental new drug application modifies the existing REMS to allow
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`prescribers to complete the REMS-required training and enrollment online.
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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.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for Juxtapid (lomitapide) was originally approved on December 21, 2012. The
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`REMS consists of elements to assure safe use, an implementation system, and a timetable for
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`submission of assessments of the REMS. Your proposed modification to the REMS allows
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`prescribers to complete the REMS-required training and enrollment online.
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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 December 21, 2012.
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`The revised REMS assessment plan should include, but is not limited to, the following:
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`1. A survey study to evaluate healthcare providers’ knowledge of the risk of hepatotoxicity
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`associated with the use of Juxtapid (lomitapide), the need to monitor liver-related
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`laboratory tests before and during treatment with Juxtapid (lomitapide) as described in
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`product labeling, and prescribers’ knowledge that FDA’s determination of the safety and
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`Reference ID: 3356376
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` NDA 203858/S-001
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` Page 2
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` efficacy of Juxtapid (lomitapide) is limited to patients diagnosed with homozygous
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` familial hypercholesterolemia.
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`a. The target level of healthcare provider knowledge for each educational goal of the
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`REMS
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`b. If the target levels for healthcare provider knowledge are not met, provide
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`possible causes for the deficiencies and proposed measures to improve
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`knowledge.
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`2. An assessment of enrollment in the Juxtapid (lomitapide) REMS Program, including the
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`following:
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`3. Metrics regarding Juxtapid (lomitapide) distribution and dispensing to assess pharmacy
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`compliance with the Juxtapid REMS:
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`a. Number of healthcare providers certified during the reporting period and
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`cumulatively.
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`i. Prescriber information, including degree, specialty, and practice setting
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`(i.e., type of practice, geographic location)
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`ii. Volume of prescriptions for each prescriber and each specialty
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`iii. A summary of the method prescribers used to enroll (fax, email, online);
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`and
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`b. Number of pharmacies certified during the reporting period and cumulatively.
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`c. Number of healthcare providers and pharmacies that had their certification
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`revoked during the reporting period and cumulatively and the reason for the
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`revocation.
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`a. The number of Juxtapid (lomitapide) orders shipped to pharmacies during the
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`reporting period and cumulatively, including number of bottles, bottle size, and
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`dosage strength.
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`b. Pharmacy compliance with Juxtapid (lomitapide) REMS Program requirements
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`(e.g., shipped to a Juxtapid (lomitapide) REMS certified pharmacy versus a non-
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`certified pharmacy).
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`c. The number of prescriptions dispensed for Juxtapid (lomitapide), including
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`quantity of tablets (mean, minimum, maximum) and dosage strength during the
`reporting period and cumulatively, overall and subset by compliance with the
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`Juxtapid (lomitapide) REMS Program requirements (e.g., received from Juxtapid
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`REMS certified versus non-certified healthcare providers, number of initial
`prescriptions dispensed without a signed attestation on the Juxtapid Prescription
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`Authorization Form). Dispensing details are to be obtained from the pharmacies.
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`Reference ID: 3356376
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` NDA 203858/S-001
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` Page 3
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` d. The number and demographics (e.g., gender, age, geographic location) of patients
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` who received Juxtapid (lomitapide) during the reporting period and annually. The
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` number is to be calculated by reconciling orders dispensed to unique patients.
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`e. Duration of therapy for patients (mean, median, range).
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`f. Report of number, length, and reasons for shipment delays to patients.
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`g. Detailed description of root cause of noncompliance with Juxtapid (lomitapide)
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`REMS Program-required dispensing and any corrective and/or preventive actions
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`taken to address noncompliance during the reporting period and cumulatively.
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`4. Summary of issues and complaints received by Juxtapid (lomitapide) REMS call center;
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`summary of resolution of the issues and complaints.
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`The requirements for assessments of an approved REMS under section 505-1(g)(3) include, with
`respect to each goal included in the strategy, an assessment of the extent to which the approved
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`strategy, including each element of the strategy, is meeting the goal or whether 1 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
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`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
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`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
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`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
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`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 203858 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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`An authorized generic drug under this NDA must have an approved REMS prior to marketing.
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`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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`Reference ID: 3356376
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` NDA 203858/S-001
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` Page 4
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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 203858 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 203858
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`PROPOSED REMS MODIFICATION
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 203858
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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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`Reference ID: 3356376
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` NDA 203858/S-001
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` Page 5
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` If you have any questions, call Kati Johnson, 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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`Amy G. Egan, MD, MPH
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`Deputy Director for Safety
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`Division of Metabolism and Endocrinology Products
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`Office of Drug Evaluation II
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`Center for Drug Evaluation and Research
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`Enclosure: REMS
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`Reference ID: 3356376
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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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`AMY G EGAN
`08/13/2013
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`Reference ID: 3356376
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