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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA 208341/S-1
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`SUPPLEMENT APPROVAL
`FULFILLMENT OF POSTMARKETING
`REQUIREMENT
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`
`Gilead Sciences, Inc.
`Attention: Grace Gill, PharmD
`Associate Manager, Regulatory Affairs
`333 Lakeside Drive
`Foster City, CA 94404
`
`
`Dear Dr. Gill:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated October 3, 2016,
`received October 3, 2016, and your amendments, submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for EPCLUSA® (sofosbuvir and velpatasvir) tablet,
`400/100 mg.
`
`This Prior Approval supplemental new drug application proposes the following changes:
`
`
`• To expand the patient population to include treatment of chronic hepatitis C virus
`infection in patient coinfected with HIV based upon the data from study GS-US-342-
`1202 (ASTRAL-5)
`
`• To update the NONCLINICAL TOXICOLOGY, section of the labeling with the results
`from the mouse carcinogenicity study.
`
`
`APPROVAL & LABELING
`
`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
`text.
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`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
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`Reference ID: 4133087
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`

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`NDA 208341/S-1
`Page 2
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`the patient package insert), 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.
`
`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/
`UCM072392.pdf.
`
`The SPL will be accessible from publicly available labeling repositories.
`
`Also within 14 days, amend all pending supplemental applications that include 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).
`
`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(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
`
`Because none of these criteria apply to your application, you are exempt from this requirement.
`
`FULFILLMENT OF POSTMARKETING REQUIREMENT
`
`We have received your submission dated October 3, 2016, containing the final report for the
`following postmarketing requirement listed in the June 28, 2016 approval letter.
`
`3092-4
`
`Submit the final clinical report and datasets for the ongoing trial GS-US-342-1202
`(ASTRAL-5), titled “A Phase 3, Open-label Study to Investigate the Efficacy and
`Safety of Sofosbuvir/GS-5816 Fixed Dose Combination for 12 weeks in Subjects
`with Chronic Hepatitis C Virus (HCV) and Human immunodeficiency Virus
`(HIV)-1 Coinfection,” to provide safety data in HIV-1/HCV co-infected subjects
`receiving sofosbuvir and velpatasvir concurrently with HIV antiretroviral therapy.
`
`
`We have reviewed your submission and conclude that the above requirement was fulfilled.
`
`We remind you that there are postmarketing requirements and a postmarketing commitment
`listed in the June 28, 2016 approval letter that are still open.
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`Reference ID: 4133087
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`

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`NDA 208341/S-1
`Page 3
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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:
`
`
`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`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/Guidance
`s/UCM443702.pdf ).
`
`You must submit final promotional materials and package insert(s), accompanied by a Form
`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. 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.
`
`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or
`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/Guidance
`s/UCM443702.pdf ).
`
`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).
`
`
`Reference ID: 4133087
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`

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`NDA 208341/S-1
`Page 4
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`If you have any questions, call Linda C. Onaga, MPH, Regulatory Project Manager, at (301)
`796-0759.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Debra Birnkrant, MD
`Director
`Division of Antiviral Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE(S):
`Content of Labeling
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`Reference ID: 4133087
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`

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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/
`----------------------------------------------------
`
`DEBRA B BIRNKRANT
`08/01/2017
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`Reference ID: 4133087
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