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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 205834/S-3
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` NDA 205834/S-5
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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` Gilead Sciences, Inc.
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` Attention: Prachi Shah, MBS, RAC
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` Associate Manager, Regulatory Affairs
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` 333 Lakeside Drive
` Foster City, CA 94404
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`Dear Ms. Shah:
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`Please refer to your Supplemental New Drug Applications (sNDA) dated and received May 15,
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`2015, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Harvoni® (ledipasvir/sofosbuvir), fixed-dose combination tablet, 90 mg/400 mg.
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`These Prior Approval supplemental new drug applications provide for the following changes:
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`NDA 205834/S-3:
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`• To expand the indication to include subjects infected with chronic hepatitis C, genotype 6
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`virus infection based upon the results of the GS-US-337-0122 (ELECTRON-2) study.
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`NDA 205834/S-5:
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`• To expand the indication to include the treatment of subjects with genotype 5, chronic
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`hepatitis C virus infection based upon the results from Study GS-US-337-1119.
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`APPROVAL & LABELING
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`We have completed our review of these supplemental applications, as amended. They are
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`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
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`upon labeling text.
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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
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling (text for the package insert and text for the
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`Reference ID: 3846181
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` NDA 205834/S-3
` NDA 205834/ S-5
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` Page 2
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` patient package insert), with the addition of any labeling changes in pending “Changes Being
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` Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed
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`labeling.
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
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`“SPL Standard for Content of Labeling Technical Qs and As at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
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` CM072392.pdf
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`date(s).
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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
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`We are waiving the pediatric study requirement from birth to less than 3 years because necessary
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`studies are impossible or highly impracticable. This is because spontaneous clearance is possible
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`and very few patients in this age group require treatment.
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`We are deferring submission of your pediatric studies for ages 3 to 17 years for this application
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`because this product is ready for approval for use in adults and the pediatric studies have not
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`been completed.
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`Your deferred pediatric study required by section 505B(a) of the FDCA is a required
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`postmarketing study. The status of the postmarketing study must be reported annually according
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`to 21 CFR 314.81 and section 505B(a)(3)(C) of the FDCA. This required study is listed below.
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`2983-1
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` Conduct a study to evaluate the pharmacokinetics, safety and treatment response (using
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` sustained virologic response) of ledipasvir/sofosbuvir in pediatric subjects 3 through 17
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` years of age with chronic hepatitis C.
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`Reference ID: 3846181
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` NDA 205834/S-3
` NDA 205834/ S-5
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` Page 3
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` Final Protocol Submission: 07/2014 (Completed)
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` 06/2018
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`Study Completion:
` Final Report Submission:
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` 02/2019
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`Reports of required pediatric postmarketing studies must be submitted as a new drug
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`application (NDA) or as a supplement to your approved NDA with the proposed labeling
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`changes that are warranted based on the data derived from the studies. When
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`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
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`the submission.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`OPDP Regulatory Project Manager
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
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`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
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`CM443702.pdf ).
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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` 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: 3846181
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` NDA 205834/S-3
` NDA 205834/ S-5
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` Page 4
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` All promotional materials that include representations about your drug product must be promptly
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` 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
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` 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
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` 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
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` eCTD format, see the draft Guidance for Industry (available at:
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Mammah Sia Borbor, Regulatory Project Manager, at (301) 796­
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`7731.
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`Sincerely,
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`{See appended electronic signature page}
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`Debra Birnkrant, MD
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`Director
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`Division of Antiviral Products
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`Office of Antimicrobial Products
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`Center for Drug Evaluation and Research
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`ENCLOSURE:
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`Content of Labeling
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`Reference ID: 3846181
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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/
`----------------------------------------------------
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`DEBRA B BIRNKRANT
`11/12/2015
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`Reference ID: 3846181
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`(
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