DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 208246 NDA APPROVAL Pfizer, Inc. 445 Eastern Point Road Groton, CT, 06340 Attention: Gary F. Perry, BS Director, Worldwide Safety and Regulatory Dear Mr. Perry: Please refer to your New Drug Application (NDA) dated April 24, 2015, received April 24, 2015, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Xeljanz (tofacitinib) Extended Release (XR) Tablets, 11 mg. This new drug application provides for the use of Xeljanz XR (tofacitinib extended release tablets), for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate, to be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). 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. EXPIRATION DATING PERIOD A 24-month expiration dating period is granted for the proposed strength of Xeljanz XR. 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 and text for the Medication Guide). 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. Reference ID: 3891137 NDA 208246 Page 2 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, as soon as they are available, but no more than 30 days after they are printed. 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 208246.” 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. 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 studies requirement for ages under the age of 2 years because necessary studies are impossible or highly impracticable. This is because Juvenile Idiopathic Arthritis (JIA) is rarely diagnosed in ages less than 2 years of age. We are deferring submission of your pediatric studies for ages 2 through 17 years for this application because this product is ready for approval for use in adults and the pediatric studies have not been completed. 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)(C) of the FDCA. These required studies are listed below: 3045-1: Conduct a study in adult healthy volunteers to assess the pharmacokinetics and bioavailability of multiple age-appropriate tofacitinib XR formulations compared to the tofacitinib IR formulation. Final Protocol Submission: Study Completion: Final Report Submission: Reference ID: 3891137 12/2016 04/2017 09/2017 NDA 208246 Page 3 3045-2: Conduct a pharmacokinetic study in adult healthy volunteers comparing multiple tofacitinib XR formulations to the tofacitinib IR formulations to select a suitable age-appropriate tofacitinib XR formulation that meets the target pharmacokinetic profile. Final Protocol Submission: Study Completion: Final Report Submission: 3045-3: 03/2018 08/2018 01/2019 Conduct a pharmacokinetic study in adult healthy volunteers to establish the equivalence of AUC and similarity in other pharmacokinetic parameters between the proposed commercial age-appropriate tofacitinib XR formulation and tofacitinib IR formulation. Final Protocol Submission: Study Completion: Final Report Submission: 07/2019 12/2019 05/2020 Submit the protocols to your IND 117389, with a cross-reference letter to this NDA. 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 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 the submission. 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: 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: Reference ID: 3891137 NDA 208246 Page 4 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). If you have any questions, call Sadaf Nabavian, Regulatory Project Manager, at (301) 796-2777. Sincerely, {See appended electronic signature page} Badrul A. Chowdhury, MD, PhD 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: 3891137 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------SARAH K YIM 02/23/2016 Signing for Badrul Chowdhury, M.D., Ph.D. Reference ID: 3891137