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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 205834/S-7
`NDA 205834/S-8
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`NDA 205834/S-9
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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
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`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 August 26, 2015,
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`received August 26, 2015, and your amendments, submitted under section 505(b) of the Federal
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` Food, Drug, and Cosmetic Act (FDCA) for Harvoni® (ledipasvir and sofosbuvir), fixed-dose
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` 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-7
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` • To expand the patient population to include subjects with genotype 1, chronic hepatitis C
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` virus infection who are liver transplant recipients
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`NDA 205834/S-8
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` • To expand the patient population to include subjects with genotype 4, chronic hepatitis C
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` virus infection who are liver transplant recipients without cirrhosis, or with compensated
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` cirrhosis
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`NDA 205834/S-9
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`• To expand the patient population to include subjects with decompensated cirrhosis who
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` have genotype 1, chronic hepatitis C virus infection.
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` APPROVAL & LABELING
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`We have completed our review of the 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-
`upon labeling text.
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`Reference ID: 3886967
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`NDA 205834/S-7
`NDA 205834/S-8
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`NDA 205834/S-9
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` Page 2
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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
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` 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
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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
`of labeling must be identical to the enclosed labeling text for the package insert and for the
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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
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`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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`Because none of these criteria apply to the current applications, you are exempt from this
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`requirement specifically in relation to the current applications.
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`Reference ID: 3886967
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`NDA 205834/S-7
`NDA 205834/S-8
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`NDA 205834/S-9
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` Page 3
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` POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
`UNDER SECTION 506B
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` We remind you of your postmarketing commitment:
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`3035-1
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`Collect, analyze, and submit data on subjects with cirrhosis including
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`decompensated cirrhosis who achieve sustained virologic response following
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`treatment with a sofosbuvir-based regimen to evaluate durability of virologic
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`response and to characterize clinical outcomes such as progression or regression
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`of liver disease, liver-related mortality, occurrence of hepatocellular carcinoma, or
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`liver failure requiring liver transplantation. Data collected should include 5 years
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`of follow-up.
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`The timetable you submitted on January 22, 2016, states that you will conduct this study
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`according to the following schedule:
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`Final Protocol Submission: 08/15 (Completed)
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`Study Completion:
`10/21
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`Final Report Submission:
`10/22
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`Submit clinical protocols to your IND 115268 for this product. Submit nonclinical and
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`chemistry, manufacturing, and controls protocols and all postmarketing final reports to this
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`NDA. In addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a
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`status summary of each commitment in your annual report to this NDA. The status summary
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`should include expected summary completion and final report submission dates, any changes in
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`plans since the last annual report, and, for clinical studies/trials, number of patients entered into
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`each study/trial. All submissions, including supplements, relating to these postmarketing
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`commitments should be prominently labeled “Postmarketing Commitment Protocol,”
`“Postmarketing Commitment Final Report,” or “Postmarketing Commitment
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`Correspondence.”
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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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`Reference ID: 3886967
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`NDA 205834/S-7
`NDA 205834/S-8
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`NDA 205834/S-9
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` Page 4
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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
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` Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`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
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`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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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 Christian Yoder, Regulatory Project Manager, at (240) 402-9990,
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`or (301) 796-1500.
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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: 3886967
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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
`02/12/2016
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`Reference ID: 3886967
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`(b
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