DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 207925 NDA APPROVAL Vertex Pharmaceuticals 50 Northern Avenue Boston, MA 02210 Attention: Alissa Minkoff, MS Senior Associate Global Regulatory Affairs Dear Ms. Minkoff: Please refer to your New Drug Application (NDA) dated September 17, 2014, received September 17, 2014, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Kalydeco (ivacaftor) oral granules. We acknowledge receipt of your amendments dated November 13, and 21, and December 10, 15, and 17, 2014, and January 26, and February 19, and 27, and March 10, 16, and 17, 2015. This new drug application provides for the use of Kalydeco (ivacaftor) oral granules for treatment of cystic fibrosis patients 2 years and older who have one of the following mutations in CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, and R117H. 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 agreed-upon labeling text and with the minor editorial revision listed below and shown in the enclosed labeling. Section 12.3 Pharmacokinetics, pg 8. “Potential for Other Drugs to Affect Ivacaftor…” “[see Dosage and Administration (2.3)” should read “[see Dosage and Administration (2.6)” 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). 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 Reference ID: 3717344 NDA 207925 Page 2 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 carton and immediate container labels that are identical to the enclosed carton and immediate container labels except with the agreed revisions to relocate the statement “Mfd for… to the bottom of the label, and substitute “oral granules” in place of “Oral Granules”, as soon as they are available. The labeling without this change may be used until the current supply is exhausted. Please submit these labels 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 Carton and Container Labels for approved NDA 207925.” Approval of this submission by FDA is not required before the labeling is used. Marketing the product with FPL that is not identical to the approved labeling text may render the product misbranded and an unapproved new drug. 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 this drug product for this indication has an orphan drug designation, you are exempt from this requirement. 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 to: Food and Drug Administration Center for Drug Evaluation and Research Office of Prescription Drug Promotion 5901-B Ammendale Road Beltsville, MD 20705-1266 Reference ID: 3717344 NDA 207925 Page 3 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). If you have any questions, call Angela Ramsey, Senior Program Management Officer, at (301) 796-2284. Sincerely, {See appended electronic signature page} Badrul A. Chowdhury, M.D., Ph.D. Director Division of Pulmonary, Allergy, and Rheumatology Products Office of Drug Evaluation II Center for Drug Evaluation and Research Enclosure(s): Content of Labeling Carton and Container Labeling Reference ID: 3717344 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------BADRUL A CHOWDHURY 03/17/2015 Reference ID: 3717344