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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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`210875Orig1s000
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`Kynmobi sublingual film
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` Generic or Proper apomorphine
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`Name:
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`Sponsor:
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`Sunovion Pharmaceuticals, Inc.
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` Approval Date: May 21, 2020
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` For the acute, intermittent treatment of “off” episodes in
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` patients with Parkinson’s disease.
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`Indication:
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`CENTER FOR DRUG EVALUATION AND RESEARCH
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`210875Orig1s000
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` CONTENTS
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` Reviews / Information Included in this NDA Review.
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` Approval Letter
` Other Action Letters
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` Labeling
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` REMS
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` Summary Review
`Officer/Employee List
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` Office Director Memo
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` Cross Discipline Team Leader Review
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`Clinical Review(s)
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` Product Quality Review(s)
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` Non-Clinical Review(s)
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`Statistical Review(s)
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` Clinical Microbiology / Virology Review(s)
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` Clinical Pharmacology Review(s)
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` Other Reviews
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` Risk Assessment and Risk Mitigation Review(s)
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` Proprietary Name Review(s)
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` Administrative/Correspondence Document(s)
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`CENTER FOR DRUG EVALUATION AND
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`RESEARCH
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`APPLICATION NUMBER:
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`210875Orig1s000
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`APPROVAL LETTER
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` NDA APPROVAL
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`Sunovion Pharmaceuticals, Inc.
`Attention: Sonya A Roeloffzen Stokowski
`Director, Global Regulatory Affairs
`84 Waterford Drive
`Marlborough, MA 01752
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`Dear Ms. Roeloffzen Stokowski:
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`Please refer to your new drug application (NDA) dated March 29, 2018, received March
`29, 2018, and your amendments, submitted pursuant to section 505(b)(2) of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for Kynmobi (apomorphine) sublingual film.
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`We acknowledge receipt of your amendment dated November 21, 2019, which
`constituted a complete response to our January 29, 2019, action letter.
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`This new drug application provides for the use of Kynmobi (apomorphine) sublingual
`film for the acute, intermittent treatment of “off” episodes in patients with Parkinson’s
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`disease.
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`APPROVAL & LABELING
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`We have completed our review of this application, as amended. It is approved, effective
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`on the date of this letter, for use as recommended in the enclosed agreed-upon
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`labeling.
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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
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`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, Patient Package Insert, and Instructions for Use) as well as
`annual reportable changes not included in the enclosed labeling. Information on
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`submitting SPL files using eLIST may be found in the guidance for industry SPL
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`Standard for Content of Labeling Technical Qs and As.2
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`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.
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`NDA 210875
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`Reference ID: 4612202
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`NDA 210875
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`Page 2
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`The SPL will be accessible via publicly available labeling repositories.
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` CARTON AND CONTAINER LABELING
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`We acknowledge your May 18, 2020, submission containing the final printed carton and
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`container labeling.
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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 (which includes new salts and new fixed combinations), new
`indications, new dosage forms, new dosing regimens, or new routes of administration
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`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.
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`We are waiving the pediatric study requirement for this application because necessary
`studies are impossible or highly impracticable. Parkinson’s disease in the pediatric
`population is extremely rare.
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`POSTMARKETING REQUIREMENTS UNDER 505(o)
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`Section 505(o)(3) of the FDCA authorizes FDA to require holders of approved drug and
`biological product applications to conduct postmarketing studies and clinical trials for
`certain purposes, if FDA makes certain findings required by the statute.
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`We have determined that an analysis of spontaneous postmarketing adverse events
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`reported under subsection 505(k)(1) of the FDCA will not be sufficient to identify an
`unexpected serious risk of drug-drug interactions caused by the norapomorphine
`glucuronide metabolite.
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`Furthermore, the active postmarket risk identification and analysis system as available
`under section 505(k)(3) of the FDCA will not be sufficient to assess this serious risk.
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`Therefore, based on appropriate scientific data, FDA has determined that you are
`required to conduct the following studies:
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`3861-1
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`Conduct in vitro studies to evaluate the drug-drug interaction potential of
`the norapomorphine glucuronide major metabolite from APL-130277 as a
`perpetrator for major CYP enzymes and transporters. Refer to the FDA
`guidance on in vitro drug interaction studies
`(https://www.fda.gov/regulatory-information/search-fda-guidance-
`documents/vitro-drug-interaction-studies-cytochrome-p450-enzyme-and-
`transporter-mediated-drug-interactions).
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
`www.fda.gov
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`Reference ID: 4612202
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`

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`NDA 210875
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`Page 3
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`The timetable you submitted on May 5, 2020, states that you will conduct this study
`according to the following schedule:
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`Completed
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`Study Completion:
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`Final Report Submission: 10/2020
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`Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of
`any study or clinical trial required under this section. This section also requires you to
`periodically report to FDA on the status of any study or clinical trial otherwise
`undertaken to investigate a safety issue. Section 506B of the FDCA, as well as 21 CFR
`314.81(b)(2)(vii) requires you to report annually on the status of any postmarketing
`commitments or required studies or clinical trials.
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`FDA will consider the submission of your annual report under section 506B and
`21 CFR 314.81(b)(2)(vii) to satisfy the periodic reporting requirement under section
`505(o)(3)(E)(ii) provided that you include the elements listed in 505(o) and
`21 CFR 314.81(b)(2)(vii). We remind you that to comply with 505(o), your annual report
`must also include a report on the status of any study or clinical trial otherwise
`undertaken to investigate a safety issue. Failure to submit an annual report for studies
`or clinical trials required under 505(o) on the date required will be considered a violation
`of FDCA section 505(o)(3)(E)(ii) and could result in enforcement action.
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`PROMOTIONAL MATERIALS
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`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-
`Electronic Format—Promotional Labeling and Advertising Materials for Human
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`Prescription Drugs.3
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`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,
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` 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
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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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` 3 For the most recent version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/media/128163/download.
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` 4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
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` 5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
`www.fda.gov
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`Reference ID: 4612202
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`NDA 210875
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`Page 4
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`If you have any questions, please contact Jack Dan, Regulatory Project Manager, at
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`jack.dan@fda.hhs.gov.
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`Sincerely,
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`{See appended electronic signature
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`page}
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` Eric Bastings, MD
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`Director (Acting)
`Division of Neurology 1
`Office of Neuroscience
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
` Content of Labeling
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`o Prescribing Information
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`o Patient Package Insert
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`o
`Instructions for Use
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
`www.fda.gov
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`Reference ID: 4612202
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`Signature Page 1 of 1
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`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/
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`ERIC P BASTINGS
`05/21/2020 09:52:32 AM
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`Reference ID: 4612202
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