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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 210455
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA APPROVAL
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`Janssen Products, LP
`Attention: Karen Gerry, BSc.
`Associate Director, Global Regulatory Affairs
`1125 Trenton-Harbourton Road
`Titusville, NJ 08560
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`Dear Ms. Gerry:
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`Please refer to your New Drug Application (NDA) dated and received September 22, 2017, and
`your amendments submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA) for SYMTUZA™ (darunavir, cobicistat, emtricitabine, and tenofovir alafenamide)
`tablets, 800/150/200/10 mg.
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`This new drug application provides for the use of SYMTUZA™ (darunavir, cobicistat,
`emtricitabine, and tenofovir alafenamide) fixed-dose combination tablets for the treatment of
`HIV-1 infection in adults:
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` who have no prior antiretroviral treatment history; or
` who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable
`antiretroviral regimen for at least 6 months and have no known substitutions associated
`with resistance to darunavir or tenofovir.
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`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.
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`WAIVER OF HIGHLIGHTS SECTION
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`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
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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 prescribing information and
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`Reference ID: 4292588
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`NDA 210455
`Page 2
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`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
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`The SPL will be accessible via publicly available labeling repositories.
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed immediate container label that are identical to the immediate container label
`submitted on June 26, 2018, 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 titled
`Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical
`Product Applications and Related Submissions Using the eCTD Specifications (May 2015,
`Revision 3). For administrative purposes, designate this submission “Final Printed Container
`Label for approved NDA 210455.” Approval of this submission by FDA is not required before
`the labeling is used.
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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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`We are waiving the pediatric study requirement in patients from birth to less than 3 years of age
`because the product would be ineffective and/or unsafe in this age group. We are waiving the
`pediatric study requirement in patients 3 years to less than 18 years of age weighing less than 40
`kg because this fixed-dose combination does not represent a meaningful therapeutic benefit over
`existing therapies and is unlikely to be used in a substantial number of patients in this age group
`due to the small number of pediatric patients in this age group.
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`We are deferring submission of your pediatric study for pediatric patients weighing at least 40 kg
`for this application because this product is ready for approval for use in adults and the pediatric
`studies have not been completed.
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`Your deferred pediatric study required by section 505B(a) of the FDCA is a required postmarketing
`study. The status of this postmarketing study must be reported annually according to 21 CFR 314.81
`and section 505B(a)(3)(C) of the FDCA. The required study is listed below.
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`3430-1
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`Conduct your deferred pediatric trial in HIV-1 infected patients weighing at least
`40 kg to assess the pharmacokinetics, safety and tolerability, and antiviral activity
`of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide fixed-dose
`combination (FDC). Study participants should be monitored for 24 weeks to
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`Reference ID: 4292588
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`NDA 210455
`Page 3
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`assess safety and durability of antiviral response. A clinical trial may not be
`required if the dosing recommendation for the FDC tablets can be supported by
`pediatric trials already conducted with the individual components and if the FDC
`produces similar exposures as the individual components.
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`Final Protocol Submission: September, 2020
`Study Completion:
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`January, 2024
`Final Report Submission:
`September, 2024
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`Submit the protocol to your IND 113456 with a cross-reference letter to this NDA.
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`Reports of this required pediatric postmarketing study must be submitted as a new drug
`application (NDA) or as a supplement to your approved NDA with the proposed labeling
`changes you believe are warranted based on the data derived from this study. When submitting
`the reports, please clearly mark your submission "SUBMISSION OF REQUIRED
`PEDIATRIC ASSESSMENTS" in large font, bolded type at the beginning of the cover letter of
`the submission.
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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, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the prescribing
`information, Medication Guide, and patient PI (as applicable) to:
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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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, accompanied by a
`Form FDA 2253. Form 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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`Reference ID: 4292588
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`

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`NDA 210455
`Page 4
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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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`If you have any questions, call Myung-Joo Patricia Hong, Senior Regulatory Project Manager, at
`(301) 796-0806.
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`Sincerely,
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`{See appended electronic signature page}
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`Debra Birnkrant, M.D.
`Director
`Division of Antiviral Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
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`Enclosures:
`Content of Labeling
`Container Labeling
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`Reference ID: 4292588
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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.
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`/s/
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`DEBRA B BIRNKRANT
`07/17/2018
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`Reference ID: 4292588
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