DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 208215/Original 1 NDA APPROVAL Gilead Sciences, Inc. Attention: Erik Berglund, M.D., Ph.D., RAC Associate Director, Regulatory Affairs 333 Lakeside Drive Foster City, CA 94404 Dear Dr. Berglund: Please refer to your New Drug Application (NDA) dated April 6, 2015, received April 7, 2015, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic (b) (4) Act (FDCA) for DESCOVY® (emtricitabine and tenofovir alafenamide), 200/25 mg fixed-dose combination tablets. We also acknowledge receipt of information related to DESCOVY® (emtricitabine, and tenofovir (b) (4) alafenamide), 200/25 mg fixed-dose combination tablets for your Gilead Access Program that was reviewed as part of this application. NDA 208215 provides for the use of DESCOVY® (emtricitabine and tenofovir alafenamide) (b) (4) 200/25 mg fixed-dose combination tablets, in combination with other antiretroviral agents, for treatment of HIV-1 infection in adults and pediatric patients 12 years of age or older. For administrative purposes, we have designated the application as follows: • • NDA 208215/Original 1 – provides for the use of 200/25 mg tablet The subject of this action letter is NDA 208215/Original 1. (b) (4) (b) (4) 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. 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 Reference ID: 3911541 NDA 208215/Original 1 Page 2 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 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. The SPL will be accessible via publicly available labeling repositories. CARTON AND IMMEDIATE CONTAINER LABELS Submit final printed immediate container label that is identical to the enclosed immediate container label, as soon as it is available, but no more than 30 days after it is printed. Please submit this label electronically according to the guidance for industry Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (June 2008). Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on heavy-weight paper or similar material. For administrative purposes, designate this submission “Final Printed Container Label for approved NDA 208215.” Approval of this submission by FDA is not required before the labeling is used. Marketing the product(s) with FPL that is not identical to the approved labeling text may render the product misbranded and an unapproved new drug. ADVISORY COMMITTEE Your application for DESCOVY was not referred to an FDA advisory committee because this drug is not the first in its class; two of the component drugs were previously approved. 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. We are waiving the pediatric study requirement in patients from birth to less than 4 weeks of age because necessary studies are impossible or highly impracticable. This is because the number of patients in this age group is too small. We are deferring submission of your pediatric studies for ages 4 weeks to less than 12 years for this application because this product is ready for approval for use in adults and the pediatric studies have not been completed. Reference ID: 3911541 NDA 208215/Original 1 Page 3 Your deferred pediatric studies required by section 505B(a) of the FDCA are required postmarketing studies. The status of these postmarketing studies must be reported annually according to 21 CFR 314.81 and section 505B(a)(3)(B) of the FDCA. These required studies are listed below. 3041-1 Conduct your deferred pediatric study in HIV-1 infected patients 4 weeks to less than 6 years to assess the pharmacokinetics, safety and tolerability, and antiviral activity of an age-appropriate formulation of emtricitabine and tenofovir alafenamide given in combination as DESCOVY fixed dose combination product. Study participants should be monitored for 24 to 48 weeks to assess safety and durability of antiviral response. Protocol Submission: Study Completion: Final Report Submission: 3041-2 December, 2017 December, 2019 April, 2020 Conduct your deferred pediatric study in HIV-1 infected, virologically suppressed patients 6 years to less than 12 years switching from other nucleoside reverse transcriptase inhibitors (NRTIs) to assess the pharmacokinetics, safety, tolerability and antiviral activity of age-appropriate DESCOVY tablets in combination with an approved third antiretroviral drug. Study participants should be monitored for 48 to 96 weeks to assess safety and durability of antiviral response. Protocol Submission: Study Completion: Final Report Submission: July, 2014 (completed) December, 2017 June, 2018 Reports of these required pediatric postmarketing studies 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. This product is appropriately labeled for use in ages 12 to less than 18 years for this indication. PROMOTIONAL MATERIALS 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 package insert, Medication Guide, and patient PI (as applicable) to: Reference ID: 3911541 NDA 208215/Original 1 Page 4 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 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 ). As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the package insert, 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. REPORTING REQUIREMENTS We remind you that you must comply with reporting requirements for an approved NDA (21 CFR 314.80 and 314.81). PDUFA V APPLICANT INTERVIEW FDA has contracted with Eastern Research Group, Inc. (ERG) to conduct an independent interim and final assessment of the Program for Enhanced Review Transparency and Communication for NME NDAs and Original BLAs under PDUFA V (‘the Program’). The PDUFA V Commitment Letter states that these assessments will include interviews with applicants following FDA action on applications reviewed in the Program. For this purpose, first-cycle actions include approvals, complete responses, and withdrawals after filing. The purpose of the interview is to better understand applicant experiences with the Program and its ability to improve transparency and communication during FDA review. ERG will contact you to schedule a PDUFA V applicant interview and provide specifics about the interview process. Your responses during the interview will be confidential with respect to the FDA review team. ERG has signed a non-disclosure agreement and will not disclose any identifying information to anyone outside their project team. They will report only anonymized results and findings in the interim and final assessments. Members of the FDA review team will be interviewed by ERG separately. While your participation in the interview is voluntary, your feedback will be helpful to these assessments. Reference ID: 3911541 NDA 208215/Original 1 Page 5 FDA BENEFIT-RISK FRAMEWORK APPLICANT INTERVIEW FDA has also contracted with Eastern Research Group, Inc. (ERG) to conduct an assessment of FDA’s initial phase implementation of the Benefit-Risk Framework (BRF) in human drug review. A key element of this evaluation includes interviews with applicants following FDA approval of New Molecular Entity (NME) New Drug Applications (NDAs) and original Biologic License Applications (BLAs). The purpose of the interview is to assess the extent to which the BRF provides applicants with a clear understanding of the reasoning behind FDA’s regulatory decisions for NME NDAs and original BLAs. ERG will contact you to schedule a BRF applicant interview and provide specifics about the interview process. Your responses during the interview will be confidential with respect to the FDA review team. ERG has signed a non-disclosure agreement and will not disclose any identifying information to anyone outside their project team. They will report only anonymized results and findings in the interim and final reports. Members of the FDA review team will be interviewed by ERG separately. While your participation in the interview is voluntary, your feedback will be helpful to this evaluation. If you have any questions, call Myung-Joo Patricia Hong, Senior Regulatory Project Manager, at (301) 796-0807. Sincerely, {See appended electronic signature page} Debra Birnkrant, M.D. Director Division of Antiviral Products Office of Antimicrobial Products Center for Drug Evaluation and Research Enclosures: Content of Labeling Container Labeling Reference ID: 3911541 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JEFFREY S MURRAY 04/04/2016 Reference ID: 3911541