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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 021825/S-003
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`Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
`FULFILLMENT OF POSTMARKETING
`REQUIREMENTS
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`
`ApoPharma Inc.
`c/o Cato Research Ltd.
`
`Attention: Lynda Sutton
`Chief Regulatory Officer
`4364 South Alston Avenue
`Durham, NC 27713-2220
`
`
`Dear Ms. Sutton:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated August 28, 2014,
`received August 28, 2014, submitted under section 505(b) of the Federal Food, Drug, and
`
` Cosmetic Act (FDCA) for Ferriprox® (deferiprone) tablets.
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`We acknowledge receipt of your amendment dated January 28 and February 13, 2015.
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` This “Prior Approval” supplemental new drug application proposes updates to the US
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`Prescribing Information (USPI) regarding QT/QTc prolongation and renal and hepatic
`impairment.
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`APPROVAL & LABELING
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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, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert and Medication
`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
`supplements, as well as annual reportable changes not included in the enclosed labeling.
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`Reference ID: 3706686
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`NDA 021825/S-003
`Page 2
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
`“SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that includes labeling changes
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
`should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
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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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`FULFILLMENT OF POSTMARKETING REQUIREMENTS
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`We have received your submissions dated July 31, 2014 (PMR 1828-4) and April 15, 2014
`(PMR 1828-5), containing the final reports for the following postmarketing requirements listed
`in the October 14, 2011 approval letter.
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`PMR 1828-4 Conduct a pharmacokinetic trial of both deferiprone and its primary 3-O
`glucuronide metabolite in subjects with hepatic impairment. This pharmacokinetic
`trial should be conducted in a population with mild to severe hepatic insufficiency
`and the number of patients enrolled in the trial should be sufficient to detect PK
`differences. The subjects enrolled in this trial should have demographics that are
`representative of the indicated population (e.g., age, weight, gender, race). Submit
`the protocol for review and concurrence prior to commencing.
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`Final Protocol Submission: September 2012
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`Trial Completion:
`February 2014
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`Final Report Submission:
`July 2014
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`Reference ID: 3706686
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`NDA 021825/S-003
`Page 3
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`PMR 1828-5 Conduct a pharmacokinetic trial of both deferiprone and its primary 3-O
`glucuronide metabolite in subjects with renal impairment. This pharmacokinetic
`trial should be conducted in a population with mild to severe renal insufficiency
`and the number of patients enrolled in the trial should be sufficient to detect PK
`differences. The subjects enrolled in this trial should have demographics that
`represent the indicated population (e.g., age, weight, gender, race) to the extent
`possible. Submit the protocol for review and concurrence prior to commencing.
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`
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`Final Protocol Submission: September 2012
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`Trial Completion:
`February 2014
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`Final Report Submission:
`July 2014
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`We have reviewed your submission and conclude that the above requirements were fulfilled.
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`We remind you that there are postmarketing requirements listed in the October 14, 2011
`approval letter that are still open.
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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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`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/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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`Reference ID: 3706686
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`NDA 021825/S-003
`Page 4
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`If you have any questions, call Amy Chi, Regulatory Project Manager, at (240) 402-0992.
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`Sincerely,
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`{See appended electronic signature page}
`
`
` Ann T. Farrell, MD
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` Director
` Division of Hematology Products
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` Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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` Medication Guide
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`Reference ID: 3706686
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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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`ANN T FARRELL
`02/24/2015
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`Reference ID: 3706686
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