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`Trade Name:
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`Generic Name:
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`CENTER FOR DRUG EVALUATION AND RESEARCH
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`Approval Package for:
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`APPLICATION NUMBER:
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`203496Orig1s000
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` Orenitram Extended Release Tablets, 0.125 mg, 0.25 mg,
`1mg, and 2.5 mg.
`
`Treprostinil
`
`United Therapeutics Corporation
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`December 20, 2013
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`Treatment of pulmonary arterial hypertension (PAH)
`(WHO Group 1) to improve exercise capacity.
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`Sponsor:
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`Approval Date:
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`Indications:
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`CENTER FOR DRUG EVALUATION AND RESEARCH
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`203496Orig1s000
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`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology / Virology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`X
`X
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`X
`X
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`X
`X
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`X
`X
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`X
`X
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`X
`X
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`
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`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`203496Orig1s000
`APPROVAL LETTER
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 203496
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA APPROVAL
`
`
`United Therapeutics Corporation
`Attention: Dean Bunce, RAC
`Executive Vice President,
`Regulatory Affairs and Compliance
`55T. W. Alexander Drive
`P.O. Box 14186
`Research Triangle Park, NC 27709
`
`Dear Mr. Bunce:
`
`Please refer to your New Drug Application (NDA) dated December 23, 2011, received
`December 27, 2011, resubmitted January 31 and August 16, 2013, under section 505(b)(1) of the
`Federal Food, Drug, and Cosmetic Act (FDCA), for Orenitram (Treprostinil) Extended Release
`Tablets, 0.125 mg, 0.25 mg, 1mg, and 2.5 mg.
`
`We acknowledge receipt of your amendments dated August 16, 20, September 13, October 8, 29,
`November 27, and December 18, 2013.
`
`The August 16, 2013, submission constituted a complete response to our March 22, 2013, action
`letter.
`
`This new drug application provides for the use of Orenitram (Treprostrinil) Extended Release
`Tablets, 0.125 mg, 0.25 mg, 1mg, and 2.5 mg for treatment of pulmonary arterial hypertension
`(PAH) (WHO Group 1) to improve exercise capacity.
`
`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
`
`CONTENT OF LABELING
`
`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, text for the
`patient package insert). Information on submitting SPL files using eLIST may be found in the
`guidance for industry SPL Standard for Content of Labeling Technical Qs and As, available at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`
`Reference ID: 3426495
`
`
`
`NDA 203496
`Page 2
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`The SPL will be accessible via publicly available labeling repositories.
`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`We acknowledge your October 29, 2013, submission containing final printed carton and
`container labels.
`
`Please submit final printed carton and immediate container labels that are identical to the carton
`and immediate container labels submitted on October 29, 2013, as soon as they are available, but
`no more than 30 days after they are printed. Please submit these labels electronically according
`to the guidance for industry Providing Regulatory Submissions in Electronic Format – Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(June 2008). Alternatively, you may submit 12 paper copies, with 6 of the copies individually
`mounted on heavy-weight paper or similar material. For administrative purposes, designate this
`submission “Final Printed Carton and Container Labels for approved NDA 203496.”
`Approval of this submission by FDA is not required before the labeling is used.
`
`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`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 in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
`
`Because this drug product for this indication has an orphan drug designation, you are exempt
`from this requirement.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`
`Reference ID: 3426495
`
`
`
`NDA 203496
`Page 3
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`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. 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.
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`If you have any questions, please call Wayne Amchin, Regulatory Project Manager, at (301)
`796-0421.
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Norman Stockbridge, MD, PhD
`Director
`Division of Cardiovascular and Renal
`Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
`
`
`
`Enclosures:
`Content of Labeling
`Carton and Container Labeling
`
`Reference ID: 3426495
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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/
`----------------------------------------------------
`
`NORMAN L STOCKBRIDGE
`12/20/2013
`
`Reference ID: 3426495
`
`