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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 205395
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`Food and Drug Administration
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` Silver Spring MD 20993
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`NDA APPROVAL
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` Janssen Products, LP
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` Attention: Karen Gerry, BSc
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` Manager, Global Regulatory Affairs
` 1125 Trenton-Harbourton Road
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` Titusville, NJ 08560
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`Dear Ms. Gerry:
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`Please refer to your New Drug Application (NDA) dated March 31, 2014 and received
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`March 31, 2014, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
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`(FDCA), for Prezcobix™ (darunavir and cobicistat) tablet, 800 mg/150 mg for oral use.
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`We also refer to our approval letter dated January 29, 2015 which contained the following errors:
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`1. The Table numbers in the Prescribing Information were incorrect.
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`This replacement approval letter incorporates the correction of the errors. The effective approval
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`date will remain January 29, 2015 the date of the original approval letter.
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`We acknowledge receipt of your amendments dated:
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`April 11, 2014
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`April 23, 2014
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`May 6, 2014
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`June 2, 2014
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`June 24, 2014
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`June 27, 2014
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`June 30, 2014
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`July 8, 2014
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`July 14, 2014
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`August 4, 2014
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`This new drug application provides for the use of Prezcobix™ (darunavir and cobicistat) in
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`combination with other antiretroviral agents for treatment of HIV-1 infection.
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`APPROVAL & LABELING
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`August 4, 2014
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`August 8, 2014
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`August 11, 2014
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`August 13, 2014
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`September 12, 2014
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`October 1, 2014
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`October 15, 2014
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`October 17, 2014
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`November 24, 2014
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`November 25, 2014
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`November 26, 2014
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`December 16, 2014
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`December 18, 2014
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`December 22, 2014
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`January 7, 2015
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`January 12, 2015
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`January 14, 2015
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`January 21, 2015
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`January 26, 2015
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`January 28, 2015
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`Reference ID: 3694997
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` NDA 205395
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` Page 2
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` We have completed our review of this application, as amended. It is approved, effective on the
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` date of this letter, for use as recommended in the enclosed agreed-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
` 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, text for the
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`patient information). Information on submitting SPL files using eLIST may be found in the
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`guidance for industry SPL Standard for Content of Labeling Technical Qs and As, available at
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`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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`IMMEDIATE CONTAINER LABEL
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`Submit the final printed immediate container label that is identical to the enclosed immediate
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`container label, as soon as it is available, but no more than 30 days after it is printed. Please
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`submit the label electronically according to the guidance for industry Providing Regulatory
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`Submissions in Electronic Format – Human Pharmaceutical Product Applications and Related
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`Submissions Using the eCTD Specifications (June 2008). Alternatively, you may submit 12
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`paper copies, with 6 of the copies individually mounted on heavy-weight paper or similar
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`material. For administrative purposes, designate this submission “Final Printed Container
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`Label for approved NDA 205395.” Approval of this submission by FDA is not required before
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`the labeling is used.
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`Marketing the product with FPL that is not identical to the approved labeling text may render the
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`product misbranded and an unapproved new drug.
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`MARKET PACKAGE
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`Please submit one market package of the drug product when it is available to the following
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`address:
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`Nina Mani
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`White Oak Building 22, Room: 6317
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`10903 New Hampshire Avenue
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`Silver Spring, Maryland
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`Use zip code 20903 if shipping via United States Postal Service (USPS).
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`Use zip code 20993 if sending via any carrier other than USPS (e.g., UPS, DHL, FedEx).
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`Reference ID: 3694997
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` NDA 205395
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` Page 3
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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 for ages, birth to less than 3 years of age because
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`there is evidence strongly suggesting that the drug product would be unsafe in this pediatric
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`group. Use of darunavir, a component of the fixed dose combination (FDC) product, is not
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`appropriate in pediatric patients < 3 years of age. This decision is based on the results of juvenile
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`rat toxicology studies that provide evidence of potential safety risk as a result of accumulation of
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`drug in the brain.
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`We are also waiving the pediatric studies requirement for children ages 3 years to less than 18
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`years weighing less than 15 kilograms (kg) because this product does not represent a meaningful
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`therapeutic benefit over existing therapies for pediatric patients in this age and weight group. In
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`addition, multiple FDC formulations would be required to be developed to accommodate the
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`various weight bands in the small number of pediatric patients below 15 kg.
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`We are deferring submission of your pediatric studies for children ages 3 years to less than 18
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`years of age and who weigh 15 kg or more for this application because the product is ready for
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` approval in adults and the pediatric studies have not been completed.
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` Your deferred pediatric studies required by section 505B(a) of the FDCA are required
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` postmarketing studies. The status of these postmarketing studies must be reported annually
` according to 21 CFR 314.81 and section 505B(a)(3)(C) of the FDCA. These required studies are
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` listed below.
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` Evaluate the pharmacokinetics, safety, and antiviral activity (efficacy) of
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` darunavir and cobicistat fixed dose combination (FDC) age-appropriate
` formulation in HIV-infected pediatric subjects 3 years to less than 6 years of age
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` and weighing at least 15 kg. The safety and antiviral activity (efficacy) of
` darunavir and cobicistat FDC age-appropriate formulation in pediatric subjects
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` should be evaluated for a minimum of 24 weeks. A clinical trial in children ages 3
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` years to less than 6 years may not be required if the dosing recommendation for
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` the FDC age-appropriate formulation can be supported by pediatric trials already
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` conducted with the individual drug products and if the age-appropriate FDC
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` produces similar exposures as the individual components.
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`Final Protocol Submission: 03/31/2020
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`12/31/2020
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`Study Completion:
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`Final Report Submission:
`12/31/2021
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` 2845-1
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`Reference ID: 3694997
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` NDA 205395
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` Page 4
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` 2845-2
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`2845-3
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` Evaluate the pharmacokinetics, safety, and antiviral activity (efficacy) of
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` darunavir and cobicistat fixed dose combination (FDC) age-appropriate
` formulation in HIV-infected pediatric subjects 6 years to less than 12 years of age
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` and weighing at least 15 kg. The safety and antiviral activity (efficacy) of
` darunavir and cobicistat FDC age-appropriate formulation in pediatric subjects
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` should be evaluated for a minimum of 24 weeks. A clinical trial in children ages 6
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` years to less than 12 years may not be required if the dosing recommendation for
` the FDC age-appropriate formulation can be supported by pediatric trials already
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` conducted with the individual drug products and if the age-appropriate FDC
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` produces similar exposures as the individual components.
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`Final Protocol Submission: 03/31/2020
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`12/31/2020
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`Study Completion:
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`Final Report Submission:
`12/31/2021
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`Evaluate the pharmacokinetics, safety, and antiviral activity (efficacy) of
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`darunavir and cobicistat fixed-dose combination (FDC) tablets in HIV-infected
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`pediatric subjects 12 years to less than 18 years of age. The safety and antiviral
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`activity (efficacy) of darunavir and cobicistat FDC tablets in pediatric subjects
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`should be evaluated for a minimum of 24 weeks. A clinical trial in children 12
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`years to less than 18 years of age may not be required if the dosing
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`recommendation for the FDC tablets can be supported by pediatric trials already
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`conducted with the individual drug products and if the FDC produces similar
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`exposures as the individual components.
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`Final Protocol Submission: 03/31/2020
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`12/31/2020
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`Study Completion:
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`Final Report Submission:
`12/31/2021
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`Submit the protocols to your IND 113198, with a cross-reference letter to this NDA.
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`Reports of these 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 you believe are warranted based on the data derived from these studies. 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
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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, in triplicate, a cover letter requesting advisory comments, the
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`proposed materials in draft or mock-up form with annotated references, and the package insert
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`to:
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`Reference ID: 3694997
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` NDA 205395
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` Page 5
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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
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` 5901-B Ammendale Road
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` Beltsville, MD 20705-1266
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
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`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
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`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
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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 Nina Mani, Regulatory Project Manager, at (240) 402-0333.
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`Sincerely,
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`{See appended electronic signature page}
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`Jeffrey S. Murray, MD, MPH
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`Deputy 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(s):
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`Content of Labeling
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`Container Labeling
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`Reference ID: 3694997
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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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`JEFFREY S MURRAY
`01/29/2015
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`Reference ID: 3694997
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