CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`203214Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`PMR/PMC Development Template
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`
`NDA/BLA #
`Product Name:
`PMR Description:
`
`203214
`Tofacitinib
`A randomized withdrawal, double blind, placebo controlled study to
`evaluate the efficacy and safety of tofacitinib in children from 2 to less
`than 18 years of age with polyarticular course of juvenile idiopathic
`arthritis.
`
`Final Protocol Submission:
`Study/Trial Completion:
`Final Report Submission:
`Other:
`
`
` March 2014
` March 2017
` September 2017
`
`
`
`
`PMR Schedule Milestones:
`
`
`
`
`1. During application review, explain why this issue is appropriate for a PMR instead of a pre-approval
`requirement. Check type below and describe.
` Unmet need
` Life-threatening condition
` Long-term data needed
` Only feasible to conduct post-approval
` Prior clinical experience indicates safety
` Small subpopulation affected
` Theoretical concern
`X Other
`
`
`
`FDA has deferred submission of 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.
`
`
`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is
`a FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new
`safety information.”
`
`Tofacitinib has not been studied in children. The goal of the study is to define the risk-benefit
`profile of tofacitinib in children from 2 to less than 18 years of age with juvenile idiopathic
`arthritis (JIA).
`
`PMR/PMC Development Template
`
`Last Updated 10/26/2012
`
`Page 1 of 3
`
`Reference ID: 3209534
`
`

`

`3. If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
` Accelerated Approval (subpart H/E)
` Animal Efficacy Rule
`X Pediatric Research Equity Act
` FDAAA required safety study/clinical trial
`
`
`
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
` Assess a known serious risk related to the use of the drug?
` Assess signals of serious risk related to the use of the drug?
` Identify an unexpected serious risk when available data indicate the potential for a serious
`risk?
`
`
`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
` Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to
`assess or identify a serious risk
`
`
`
` Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the
`FDA is required to establish under section 505(k)(3) has not yet been established and is thus
`not sufficient to assess this known serious risk, or has been established but is nevertheless not
`sufficient to assess or identify a serious risk
`
` Study: all other investigations, such as investigations in humans that are not clinical trials as
`defined below (e.g., observational epidemiologic studies), animal studies, and laboratory
`experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a
`serious risk
`
`
`
`
`
` Clinical trial: any prospective investigation in which the sponsor or investigator determines
`the method of assigning investigational product or other interventions to one or more human
`subjects?
`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the
`study or trial will be performed in a subpopulation, list here.
`A randomized withdrawal, double blind, placebo controlled study to evaluate the efficacy
`and safety of tofacitinib in children from 2 to less than 18 years of age with polyarticular
`course of juvenile idiopathic arthritis.
`
`
`Required
` Observational pharmacoepidemiologic study
` Registry studies
`X Primary safety study or clinical trial
` Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
` Thorough Q-T clinical trial
` Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`
`PMR/PMC Development Template
`
`Last Updated 10/26/2012
`
`Page 2 of 3
`
`Reference ID: 3209534
`
`

`

`Continuation of Question 4
`
`
` Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
` Pharmacokinetic studies or clinical trial
` Drug interaction or bioavailability studies or clinical trials
` Dosing trial
` Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
` Meta-analysis or pooled analysis of previous studies/clinical trials
` Immunogenicity as a marker of safety
` Other (provide explanation)
`
`
`Agreed upon:
` Quality study without a safety endpoint (e.g., manufacturing, stability)
` Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease,
`background rates of adverse events)
` Clinical trials primarily designed to further define efficacy (e.g., in another condition,
`different disease severity, or subgroup) that are NOT required under Subpart H/E
` Dose-response study or clinical trial performed for effectiveness
` Nonclinical study, not safety-related (specify)
`
` Other
`
`
`
`
`
`5. Is the PMR clear, feasible, and appropriate?
`X Does the study/clinical trial meet criteria for PMRs or PMCs?
`X Are the objectives clear from the description of the PMR/PMC?
`X Has the applicant adequately justified the choice of schedule milestone dates?
`X Has the applicant had sufficient time to review the PMRs, ask questions, determine feasibility,
`and contribute to the development process?
`
`
`PMR/PMC Development Coordinator:
`X This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine
`the safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug
`quality.
`
`
`_______________________________________
`(signature line for BLAs)
`
`PMR/PMC Development Template
`
`Last Updated 10/26/2012
`
`Page 3 of 3
`
`Reference ID: 3209534
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`SALLY M SEYMOUR
`10/26/2012
`
`Reference ID: 3209534
`
`

`

`PMR/PMC Development Template
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`
`NDA/BLA #
`Product Name:
`PMR Description:
`
`203214
`Tofacitinib
`A multiple dose pharmacokinetic study in children from 2 to less than
`18 years of age with juvenile idiopathic arthritis (JIA)
`
`Final Protocol Submission:
`Study/Trial Completion:
`Final Report Submission:
`Other:
`
`
` November 2012
` March 2014
` September 2014
`
`.
`
`
`PMR Schedule Milestones:
`
`
`
`
`1. During application review, explain why this issue is appropriate for a PMR instead of a pre-approval
`requirement. Check type below and describe.
` Unmet need
` Life-threatening condition
` Long-term data needed
` Only feasible to conduct post-approval
` Prior clinical experience indicates safety
` Small subpopulation affected
` Theoretical concern
`X Other
`
`
`
`FDA has deferred submission of 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.
`
`
`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is
`a FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new
`safety information.”
`
`Tofacitinib has not been studied in children. The goal of the study is to identify a pediatric dose for
`further study to define the risk-benefit profile of tofacitinib in children from 2 to less than 18
`years of age with juvenile idiopathic arthritis (JIA).
`
`PMR/PMC Development Template
`
`Last Updated 10/26/2012
`
`Page 1 of 3
`
`Reference ID: 3209528
`
`

`

`3. If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
` Accelerated Approval (subpart H/E)
` Animal Efficacy Rule
`X Pediatric Research Equity Act
` FDAAA required safety study/clinical trial
`
`
`
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
` Assess a known serious risk related to the use of the drug?
` Assess signals of serious risk related to the use of the drug?
` Identify an unexpected serious risk when available data indicate the potential for a serious
`risk?
`
`
`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
` Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to
`assess or identify a serious risk
`
`
`
` Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the
`FDA is required to establish under section 505(k)(3) has not yet been established and is thus
`not sufficient to assess this known serious risk, or has been established but is nevertheless not
`sufficient to assess or identify a serious risk
`
` Study: all other investigations, such as investigations in humans that are not clinical trials as
`defined below (e.g., observational epidemiologic studies), animal studies, and laboratory
`experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a
`serious risk
`
`
`
`
`
` Clinical trial: any prospective investigation in which the sponsor or investigator determines
`the method of assigning investigational product or other interventions to one or more human
`subjects?
`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the
`study or trial will be performed in a subpopulation, list here.
`A multiple dose pharmacokinetic study in children from 2 to less than 18 years of age with
`juvenile idiopathic arthritis (JIA).
`
`
`Required
` Observational pharmacoepidemiologic study
` Registry studies
` Primary safety study or clinical trial
` Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
` Thorough Q-T clinical trial
` Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`
`PMR/PMC Development Template
`
`Last Updated 10/26/2012
`
`Page 2 of 3
`
`Reference ID: 3209528
`
`

`

`Continuation of Question 4
`
`
` Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
`X Pharmacokinetic studies or clinical trial
` Drug interaction or bioavailability studies or clinical trials
`X Dosing trial
` Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
` Meta-analysis or pooled analysis of previous studies/clinical trials
` Immunogenicity as a marker of safety
` Other (provide explanation)
`
`
`Agreed upon:
` Quality study without a safety endpoint (e.g., manufacturing, stability)
` Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease,
`background rates of adverse events)
` Clinical trials primarily designed to further define efficacy (e.g., in another condition,
`different disease severity, or subgroup) that are NOT required under Subpart H/E
` Dose-response study or clinical trial performed for effectiveness
` Nonclinical study, not safety-related (specify)
`
` Other
`
`
`
`
`
`5. Is the PMR clear, feasible, and appropriate?
`X Does the study/clinical trial meet criteria for PMRs or PMCs?
`X Are the objectives clear from the description of the PMR/PMC?
`X Has the applicant adequately justified the choice of schedule milestone dates?
`X Has the applicant had sufficient time to review the PMRs, ask questions, determine feasibility,
`and contribute to the development process?
`
`
`PMR/PMC Development Coordinator:
`X This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine
`the safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug
`quality.
`
`
`_______________________________________
`(signature line for BLAs)
`
`PMR/PMC Development Template
`
`Last Updated 10/26/2012
`
`Page 3 of 3
`
`Reference ID: 3209528
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`SALLY M SEYMOUR
`10/26/2012
`
`Reference ID: 3209528
`
`

`

`PMR/PMC Development Template
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`
`NDA/BLA #
`Product Name:
`PMR Description:
`
`203214
`Tofacitinib
`Randomized controlled clinical trial to evaluate the long term safety of
`tofacitinib in patients with rheumatoid arthritis. The trial will include
`two doses of tofacitinib and an active comparator. The trial will be of
`sufficient size and duration to evaluate safety events of interest,
`including cardiovascular adverse events, opportunistic infections, and
`malignancy.
`
`Final Protocol Submission:
`Study/Trial Completion:
`Final Report Submission:
`Other:
`
`
` March 2013
` December 2019
` June 2020
`
`
`
`
`PMR Schedule Milestones:
`
`
`
`
`1. During application review, explain why this issue is appropriate for a PMR instead of a pre-approval
`requirement. Check type below and describe.
` Unmet need
` Life-threatening condition
`X Long-term data needed
` Only feasible to conduct post-approval
` Prior clinical experience indicates safety
` Small subpopulation affected
`X Theoretical concern of long-term cardiovascular morbidity and mortality resulting from
`tofacitinib-induced elevations in total and LDL cholesterol
` Other
`
`
`
`The review has determined a favorable risk benefit profile of tofacitinib for approval based on the
`available data. However, the use of tofacitinib was associated with a potential safety signal of
`malignancy and serious infections and with laboratory abnormalities to include elevations in total
`and LDL cholesterol. To better define the long-term safety profile of tofacitinib as a new molecular
`entity, we have determined that only a clinical trial (rather than a nonclinical or observational study)
`will be sufficient to assess a signal of a serious risk of cardiovascular events, serious infections, and
`malignancy as a required post-marketing trial.
`
`
`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is
`a FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new
`safety information.”
`
`PMR/PMC Development Template
`
`Last Updated 10/26/2012
`
`Page 1 of 3
`
`Reference ID: 3209521
`
`

`

`The goal of the trial will be to address the risk of major adverse cardiovascular events, malignancy
`and opportunistic infections.
`
`3. If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
` Accelerated Approval (subpart H/E)
` Animal Efficacy Rule
` Pediatric Research Equity Act
`X FDAAA required safety study/clinical trial
`
`
`
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
`X Assess a known serious risk related to the use of the drug?
`X Assess signals of serious risk related to the use of the drug?
` Identify an unexpected serious risk when available data indicate the potential for a serious
`risk?
`
`
`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
` Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to
`assess or identify a serious risk
`
`
`
`
`
` Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the
`FDA is required to establish under section 505(k)(3) has not yet been established and is thus
`not sufficient to assess this known serious risk, or has been established but is nevertheless not
`sufficient to assess or identify a serious risk
`
` Study: all other investigations, such as investigations in humans that are not clinical trials as
`defined below (e.g., observational epidemiologic studies), animal studies, and laboratory
`experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a
`serious risk
`
` X
`
` Clinical trial: any prospective investigation in which the sponsor or investigator determines the
`method of assigning investigational product or other interventions to one or more human
`subjects?
`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the
`study or trial will be performed in a subpopulation, list here.
`Randomized controlled clinical trial to evaluate safety events of interest, including
`cardiovascular adverse events, opportunistic infections, and malignancy in patients with
`rheumatoid arthritis. The trial should include two doses of tofacitinib and an active
`comparator.
`
`PMR/PMC Development Template
`
`Last Updated 10/26/2012
`
`Page 2 of 3
`
`Reference ID: 3209521
`
`

`

`
`Required
` Observational pharmacoepidemiologic study
` Registry studies
`X Primary safety study or clinical trial
` Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
` Thorough Q-T clinical trial
` Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`Continuation of Question 4
`
`
` Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
` Pharmacokinetic studies or clinical trials
` Drug interaction or bioavailability studies or clinical trials
` Dosing trials
` Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
` Meta-analysis or pooled analysis of previous studies/clinical trials
` Immunogenicity as a marker of safety
` Other (provide explanation)
`
`
`Agreed upon:
` Quality study without a safety endpoint (e.g., manufacturing, stability)
` Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease,
`background rates of adverse events)
` Clinical trials primarily designed to further define efficacy (e.g., in another condition,
`different disease severity, or subgroup) that are NOT required under Subpart H/E
` Dose-response study or clinical trial performed for effectiveness
` Nonclinical study, not safety-related (specify)
`
` Other
`
`
`
`
`
`5. Is the PMR clear, feasible, and appropriate?
`X Does the study/clinical trial meet criteria for PMRs or PMCs?
`X Are the objectives clear from the description of the PMR/PMC?
`X Has the applicant adequately justified the choice of schedule milestone dates?
`X Has the applicant had sufficient time to review the PMRs, ask questions, determine feasibility,
`and contribute to the development process?
`
`
`PMR/PMC Development Coordinator:
`X This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine
`the safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug
`quality.
`
`
`_______________________________________
`(signature line for BLAs)
`
`PMR/PMC Development Template
`
`Last Updated 10/26/2012
`
`Page 3 of 3
`
`Reference ID: 3209521
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`SALLY M SEYMOUR
`10/26/2012
`
`Reference ID: 3209521
`
`

`

`
`
`STUDY ENDPOINT REVIEW
`
`
`
`
`
`
`SEALD TRACKING NUMBER AT 2012-116
`
`
`APPLICATION NUMBER NDA 203214
`
`
`
`
`
`
`
`
`DATE OF CONSULT REQUEST October 10, 2012
`
`
`REVIEW COMPLETION DATE October 22, 2012
`
`
`
`
`
`
`
`
`
`
`SEALD REVIEWER
`Elektra Papadopoulos
`
`
`SEALD DIRECTOR
`Laurie Burke
`
`
`DPARP MEDICAL OFFICER Nikolay Nikolov
`
`
`DPARP PROJECT MANAGER
`Philantha Bowen
`
`
`SPONSOR
`Pfizer
`
`
`DRUG
`Tofacitinib
`
`
`
`
`CLINICAL OUTCOME ASSESSMENT TYPE
`PRO
`
`
` Generic health status
`
`
`
`SF-36 Version 2 (one week recall period)
`
`
`
`
`
`
`
`
`
`Patients with moderately to severely active
`rheumatoid arthritis
`
`
`
`
`ENDPOINT(S) CONCEPT(S)
`
`MEASURE(S)
`
`INTENDED POPULATION(S)
`
`
`
`
`
`Reference ID: 3206546
`
`

`

`SEALD Review
`Elektra J. Papadopoulos, MD, MPH
`NDA 203214
`SF-36 (generic health status) for the indication rheumatoid arthritis
`
`
`This abbreviated Study Endpoints and Labeling Development (SEALD) review is provided as a
`response to a request for consultation by the Division of Pulmonary, Allergy, and Rheumatology
`Products (DPARP) regarding NDA 203214 for tofacitinib for the treatment of adult patients with
`moderately to severely active rheumatoid arthritis (RA).
`
`DPARP included the following questions to SEALD:
`
`
`(1) Is the SF-36 PCS or MCS acceptable for inclusion in the Clinical Studies section of
`tofacitinib labeling? If not, provide the rationale.
`
`
`(2) If any domains of the SF-36 (e.g. PF10) are considered acceptable, please provide a
`rationale for use of the domain score for labeling claims in RA.
`
`
`SEALD response:
`
`The SF-36 Version 2 Acute is a self-reported (1 week recall period), thirty-six item generic
`health status instrument that assesses eight dimensions of health: physical functioning; role-
`physical; bodily pain; general health; vitality; social functioning; role-emotional; and mental
`health. In addition to measuring the eight health domains, a physical component summary score
`(PCS) and mental component summary score (MCS) can be obtained. A single overall score for
`the SF-36 does not exist. A copy of the instrument version used in the clinical trials is appended.
`
`The SF-36 PCS combines weighted scores across the following four domains: physical
`functioning (i.e., SF-36 PF10); role-physical; bodily pain; and general health, but the score also
`has contributions from the remaining four domains (i.e., the “mental domains”). The SF-36 MCS
`combines weighted scores across the following four domains: vitality; social functioning; role-
`emotional; and mental health, but also has contributions from the remaining four domains (i.e.,
`the “physical domains”). Therefore, neither the PCS nor the MCS should be referenced in
`labeling because the actual concepts measured are undefined and cannot be described in a way
`that is meaningful. (See also the SF-36 measurement model appended to this review.)
`
`The physical functioning domain (SF-36 PF-10) includes 10 items. The SF-36 PF-10, as a
`generic instrument, includes lower limb activities such as walking and climbing stairs, upper
`limb activities such as carrying groceries, and small joint activities (limitations with bathing and
`dressing). Therefore, the SF-36 PF-10 assesses “patient perceived limitations in physical
`activities” in patients with RA in whom both large and small joints are typically affected.
`
`At face value, the SF-36 PF-10 appears to target patient-reported limitations in specified physical
`activities. The PF-10 does not ask the patient whether or not the activity was actually performed.
`Furthermore, it does not adequately cover important aspects of physical functioning that are
`relevant to RA patients (e.g., typing, opening jars). Therefore, the SF-36 PF-10 would not
`support a “physical functioning” claim in RA, but rather a claim of “perceived limitations in
`
`
`
`Reference ID: 3206546
`
`2
`
`
`
`
`
`

`

`SEALD Review
`Elektra J. Papadopoulos, MD, MPH
`NDA 203214
`SF-36 (generic health status) for the indication rheumatoid arthritis
`
`
`physical activities.” A clinically meaningful and statistically robust treatment effect on the SF-36
`PF-10 domain score might be described in product labeling as follows.
`
`
`Drug A-treated patients achieved greater improvements from baseline than placebo-treated
`patients [or active comparator] in self-reported limitations in physical activities as
`measured by a 10-item subscale (PF-10) of the SF-36, a generic health status instrument.
`
`We also recommend exploratory analysis of all PF-10 items individually to make sure that there
`is no decrement in any of the 10 items contributing to the PF-10 total score.
`
`
`
`Reference ID: 3206546
`
`3
`
`
`
`
`
`

`

`SEALD Review
`Elektra J. Papadopoulos, MD, MPH
`NDA 203214
`SF-36 (generic health status) for the indication rheumatoid arthritis
`
`
`APPENDICES
`
`
`
`
`Reference ID: 3206546
`
`4
`
`
`
`
`
`

`

`SEALD Review
`
`Elektra J. Papadopoulos, 1W), MPH
`NDA 203214
`
`SF-36 (generic health status) for the indication rheumatoid arthritis
`
`Figue 2.1
`
`Short Fonn Health Status Measurement Model
`
` ‘ \
`
`Nate. Item numbers cmopond toSF-36v2 item numbers. 8F-12v2 itemmindicoted hfifll health
`dumainncaluoonm’bmemthoacofingofbodlmel’hydcdandMennlComponentSummarymm.$:ales
`muibufingmonmthewaflngofhxmmrymmmmhdicamdhyammfinzmfid line(—).Scale¢
`cmflibufingmmemhgofmesummuymeammmalumdegmeminficaedbyadomdfim(------).
`J
`
`Reference ID: 3206546
`
`

`

`SEALD Review
`
`Elektra J. Papadopoulos, MD, MPH
`NDA 203214
`
`SF-36 (generic health status) for the indication rheumatoid arthritis
`
`CP-690,550
`A3921045
`Final Protocol Amendment 2, 12 March 2010
`
`
`
`Appendix 9. SF-36 Version 2 (Acute)
`
`Reference ID: 3206546
`
`PFIZER CONFIDENTIAL
`
`Page 78 of 157
`Page 78
`
`

`

`SEALD Review
`
`Elektra J. Papadopoulos, MD, MPH
`NDA 203214
`
`SF-36 (generic health status) for the indication rheumatoid arthritis
`
`CP—690,550
`A392 1045
`Final Protocol Amendment 2, 12 March 2010
`
`
`
`Reference ID: 3206546
`
`PFIZER CONFDDENTIAL
`Page 79 of 157
`Page 79
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`

`

`SEALD Review
`
`Elektra J. Papadopoulos, MD, MPH
`NDA 203214
`
`SF-36 (generic health status) for the indication rheumatoid arthritis
`
`CP-690.550
`A3921045
`Final Protocol Amendment 2, 12 March 2010
`
`
`
`Reference ID: 3206546
`
`PFIZER CONFIDENTIAL
`Page 80 of 157
`Page 80
`
`

`

`SEALD Review
`
`Elektra J. Papadopoulos, MD, MPH
`NDA 203214
`
`SF-36 (generic health status) for the indication rheumatoid arthritis
`
`
`
`SF-3»6v2'm Health Survey @1996. 2000 by QualityMetric Incorporated and Medical Outcomes Trust. Ml
`Rights Reserved.
`SF-36® is a registered trademark of Medical Outcomes Trust.
`(SF-36v2 Acute, US Version 2.0)
`
`THANK YOU FOR COMPLETING THESE QUESTIONS!
`
`Reference ID: 3206546
`
`PFIZER CONFIDENTIAL
`Page 81 of 157
`Page 81
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ELEKTRA J PAPADOPOULOS
`10/22/2012
`
`LAURIE B BURKE
`10/22/2012
`
`Reference ID: 3206546
`
`

`

`
`
`
`
`Philantha Montgomery Bowen, Regulatory Project Manager
`Division of Pulmonary, Allergy, and Rheumatology Products
`(DPARP)
`
`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`Memorandum
`
`Date:
`October 2, 2012
`
`
`To:
`
`
`
`
`
`
`From:
`
`
`
`
`
`
`
`
`CC:
`
`
`
`Subject:
`
`
`
`
`OPDP has reviewed the proposed Package Insert (PI), Medication Guide, and
`Carton and Container Labeling for Xeljanz submitted for consult on November
`10, 2011. We offer the following comments on the proposed labeling.
`
`OPDP’s comments on the PI are based on the proposed draft labeling titled
`“NDA 203214 – DPARP draft Label (9-18-12).doc” that was sent via email from
`DPARP to OPDP on September 18, 2012. OPDP’s comments on the PI are
`provided directly in the marked-up document attached (see below).
`
`OPDP’s comments on the Medication Guide are based on the proposed draft
`labeling titled “tofacitinib (XELJANZ) 203214 DMPP MG Sep-2012 clean.doc”
`that was sent via email from DMPP to DPARP on September 27, 2012 and to
`OPDP on October 1, 2012.
`
`OPDP’s comments on the Medication Guide are provided directly in the marked-
`up document attached (see below).
`
`Matthew Falter, Pharm.D., Regulatory Review Officer, Division of
`Consumer Drug Promotion (DCDP), Office of Prescription Drug
`Promotion (OPDP)
`
`Roberta Szydlo, R.Ph., Regulatory Review Officer, Division of
`Professional Drug Promotion (DPDP), OPDP
`
`Lisa Hubbard, Group Leader, DPDP, OPDP
`Twyla Thompson, Acting Group Leader, DCDP, OPDP
`
`
`NDA 203214
`OPDP labeling comments for XELJANZ® (tofacitinib) tablets for oral
`administration (Xeljanz)
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3198158
`
`1
`
`

`

`
`
`
`
`
`\\cdsesub1\EVSPROD\NDA203214\\0038\m1\us\contain-tofa10180.pdf
`\\cdsesub1\EVSPROD\NDA203214\\0038\m1\us\contain-tofa1060.pdf
`\\cdsesub1\EVSPROD\NDA203214\\0038\m1\us\contain-tofa5180.pdf
`\\cdsesub1\EVSPROD\NDA203214\\0038\m1\us\contain-tofa560.pdf
`
`OPDP has also reviewed the proposed carton and container labeling submitted
`by the sponsor on August 14, 2011, and located in the EDR at:
`
`
`
`OPDP has no comments at this time on the proposed carton and container
`labeling.
`
`Thank you for the opportunity to comment on the proposed labeling.
`
`If you have any questions regarding patient labeling please contact Matt Falter at
`(301) 796-2287 or matthew.falter@fda.hhs.gov.
`
`If you have any questions regarding professional labeling please contact Roberta
`Szydlo at (301) 796-5389 or roberta.szydlo@fda.hhs.gov.
`
`
`
`
`
`Reference ID: 3198158
`
`2
`
`46 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this
`page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ROBERTA T SZYDLO
`10/02/2012
`
`MATTHEW J FALTER
`10/02/2012
`
`Reference ID: 3198158
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Medical Policy Initiatives
`Division of Medical Policy Programs
`
`PATIENT LABELING REVIEW
`September 27, 2012
`
`Badrul Chowdhury, MD,
`Director
`Division of Pulmonary, Allergy, Rheumatology Products
`(DPARP)
`LaShawn Griffiths, MSHS-PH, BSN, RN
`Associate Director for Patient Labeling
`Division of Medical Policy Programs (DMPP)
`
`Melissa Hulett, RN, BSN, MSBA
`Team Leader, Patient Labeling Team
`Division of Medical Policy Programs (DMPP)
`
`Sharon W. Williams, RN, BSN, MSN
`Patient Labeling Reviewer
`Division of Medical Policy Programs (DMPP)
`DMPP Review of Patient Labeling: Medication Guide (MG)
`
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`Drug Name (established
`name):
`
`XELJANZ (tofacitinib)
`
`Dosage Form and Route: Tablets
`
`
`NDA 203214
`
`Application
`Type/Number:
`
`
`Applicant:
`
`
`
`
`
`
`
`Pfizer Inc.
`
`
`
`
`
`Reference ID: 3195309
`
`1
`
`

`

`1
`
`INTRODUCTION
`On October 21, 2011, Pfizer Inc. submitted an original New Drug Application
`indicated for the treatment of adult patients with moderately to severely active
`rheumatoid arthritis who have had an inadequate response to methotrexate.
`On November 10, 2011 the Division of Pulmonary, Allergy, and Rheumatology
`Products (DPARP) requested