`
`CENTER FOR DRUG EVALUATION AND RESEARCH
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`Approval Package for:
`
`APPLICATION NUMBER:
`
`214324Orig1s000
`
`
` Tyvaso DPI inhalation powder
`Trade Name:
`Treprostinil
`Generic or Proper
`Name:
`United Therapeutics Corp.
`
`Sponsor:
`
`May 23, 2022
`Approval Date:
`
`Tyvaso DPI is a prostacyclin mimetic indicated for the
`Indication:
`
`treatment of:
` Pulmonary arterial hypertension (PAH; WHO
`Group 1) to improve exercise ability. Studies with
`Tyvaso establishing effectiveness predominately
`included patients with NYHA Functional Class III
`symptoms and etiologies of idiopathic or heritable
`PAH (56%) or PAH associated with connective
`tissue diseases (33%).
`
` Pulmonary hypertension associated with interstitial
`lung disease (PH-ILD; WHO Group 3) to improve
`exercise ability. The study with Tyvaso establishing
`effectiveness predominately included patients with
`etiologies of idiopathic interstitial pneumonia (IIP)
`(45%) inclusive of idiopathic pulmonary fibrosis
`(IPF), combined pulmonary fibrosis and emphysema
`(CPFE) (25%), and WHO Group 3 connective tissue
`disease (22%).
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`2143240rig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
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`X X X
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`0
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`Administrative/Correspondence Document(s
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`‘
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`Office Director Memo
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`Cross Discipline Team Leader Review
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`Clinical Microbiolog
`
`DY
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`

`

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`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`214324Orig1s000
`
`
`APPROVAL LETTER
`
`

`

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`NDA 214324
`
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`NDA APPROVAL
`
`
`United Therapeutics Corp.
`Attention: Sarah Gemberling, PhD, RAC
`Manager, Regulatory Affairs
`55 TW Alexander Drive, PO Box 14186
`Research Triangle Park, NC 27709
`
`
`Dear Dr. Gemberling:
`
`Please refer to your new drug application (NDA) dated April 16, 2021, received
`April 16, 2021, and your amendments, submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for Tyvaso DPI (treprostinil) inhalation powder.
`
`We acknowledge receipt of your amendment dated December 23, 2021, which
`constituted a complete response to our October 15, 2021, action letter.
`
`We acknowledge receipt of your major amendment dated February 18, 2022, which
`extended the goal date by three months.
`
`This NDA provides for the use of Tyvaso DPI (treprostinil) inhalation powder for the
`treatment of pulmonary arterial hypertension (PAH; WHO Group I) and pulmonary
`hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3), to
`improve exercise ability.
`
`APPROVAL & LABELING
`
`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.
`
`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
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
`Prescribing Information, and Instructions for Use) as well as annual reportable changes
`not included in the enclosed labeling. Information on submitting SPL files using eLIST
`
`1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`
`Reference ID: 4987774
`
`

`

`NDA 214324
`Page 2
`
`
`may be found in the guidance for industry SPL Standard for Content of Labeling
`Technical Qs and As.2
`
`The SPL will be accessible via publicly available labeling repositories.
`
`CARTON AND CONTAINER LABELING
`
`Submit final printed carton and container labeling that are identical to the enclosed
`carton and container labeling , as soon as they are available, but no more than 30 days
`after they are printed. Please submit these labeling electronically according to the
`guidance for industry Providing Regulatory Submissions in Electronic Format — Certain
`Human Pharmaceutical Product Applications and Related Submissions Using the eCTD
`Specifications. For administrative purposes, designate this submission “Final Printed
`Carton and Container Labeling for approved NDA 214324.” Approval of this
`submission by FDA is not required before the labeling is used.
`
`DATING PERIOD
`
`Based on the stability data submitted to date, the expiry dating period for Tyvaso DPI
`(treprostinil) inhalation powder shall be 18 months from the date of manufacture when
`stored at 2°C to 8°C (36°F to 46°F).
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`new active ingredients (which includes new salts and new fixed combinations), 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 has an orphan drug designation for the treatment of PAH,
`you are exempt from this requirement for the PAH indication only.
`
`We are waiving the pediatric study requirement for the treatment of PH-ILD because
`necessary studies are impossible or highly impracticable considering the number of
`pediatric patients with PH-ILD is extremely rare.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information about submitting promotional materials, see the
`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
`
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4987774
`
`

`

`NDA 214324
`Page 3
`
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`Electronic Format—Promotional Labeling and Advertising Materials for Human
`Prescription Drugs.3
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials,
`and the Prescribing Information, at the time of initial dissemination or publication,
`accompanied by a Form FDA 2253. Form FDA 2253 is available at FDA.gov.4
`Information and Instructions for completing the form can be found at FDA.gov.5
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`Your product is a Part 3 combination product (21 CFR 3.2(e)); therefore, you must also
`comply with postmarketing safety reporting requirements for an approved combination
`product (21 CFR 4, Subpart B). Additional information on combination product
`postmarketing safety reporting is available at FDA.gov.6
`
`If you have any questions, please call Brian Cooney, Regulatory Project Manager, at
`(301) 796-0886.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Norman Stockbridge, MD, PhD
`Director
`Division of Cardiology and Nephrology
`Office of Cardiology, Hematology, Endocrinology, and
`Nephrology
`Office of New Drugs
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE(S):
`• Content of Labeling
`o Prescribing Information
`Instructions for Use
`o
`• Carton and Container Labeling
`
`
`
`
`3 For the most recent version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/media/128163/download.
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`6 https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-
`reporting-combination-products
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4987774
`
`

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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/
`------------------------------------------------------------
`
`NORMAN L STOCKBRIDGE
`05/23/2022 08:55:05 AM
`
`Reference ID: 4987774
`
`(b)
`(4)
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