(PsA) Arthritis Advisory Committee

123 Pages·2017·2.1 MB·English

Author: Nancy McKay Ready for QC
RevInie QwCe d
QC Complete
Source: SME, see author
Date
30 July 2017
25 July 2017
Slide Coordinators Reviewed
(Carol Connell/Ann Wouters)
Graphics
Ready for QC
(Crystal Huntoon)
In QC
QC Coordinator
(Ann Fairbank/Laura Brown) Date
Graphics
QC Edits
(Crystal Huntoon)
XELJANZ® (tofacitinib)
QC Complete
QC Coordinator
(Ann Fairbank/Laura Brown) Date for the Treatment of Psoriatic Arthritis (PsA)
Graphics
(Crystal Huntoon)
Arthritis Advisory Committee (AAC)
QC Coordinator In RE-QC August 3, 2017
(Ann Fairbank/Laura Brown) Date
FDA White Oak Campus
Silver Spring, MD
MA-1
Author: Nancy McKay
ReaInd yQ Cfo r QC
Reviewed
Source: SME, see author
QC CDoamtep lete
25 July 2017
30 July 2017
Introduction
Nancy McKay
Director, Regulatory Affairs
Pfizer Inc
MA-2
Author: Nancy McKay RReeavideyIwn fQeodCr QC
Source: QC CoDmaptele te
30 2J5u Jlyu l2y 0210717
Overview of Presentation
Topic Presenter
Nancy McKay
Introduction Director, Regulatory Affairs
Pfizer Inc
Philip Mease, MD, MACR
Psoriatic Arthritis:
Director, Rheumatology Research, Swedish-Providence-St.
A Physician’s Perspective/ Joseph Health Systems
Unmet Medical Need Clinical Professor, University of Washington School of Medicine,
Seattle, WA
Keith Kanik, MD, FACR
Tofacitinib PsA Development
Senior Director, Global Clinical Lead PsA
Program and Efficacy Inflammation and Immunology
Pfizer Inc
Daniela Graham, MD
Clinician, PsA Development Program
Tofacitinib PsA Safety
Inflammation and Immunology
Pfizer Inc
Thomas Jones, MD
Risk Management Senior Director, Safety Risk Management
Pfizer Inc
Michael Corbo, PhD
Senior VP, Chief Development Officer
Benefit:Risk and Conclusions
Inflammation and Immunology
Pfizer Inc
MA-3
Author: Jim Clark
Ready for QC
RevIine QwCe d
Source: Flanagan ME et al, J
QC CDoamtep lete
Med Chem 2010; 53:8468-8484
3 205 J Juullyy 22001177
Tofacitinib is an Oral, Small Molecule JAK Inhibitor
 JAK inhibition is partial
and reversible and interferes
Tofacitinib
with signaling of cytokines
important in psoriatic arthritis
H
N
N
 Effective oral drug with
manageable safety profile
N
and efficacy similar to
TNF-inhibitors O
N
CN
 Provides an oral option to
N
address unmet needs for
the treatment of patients
with active PsA
Flanagan ME et al, J Med Chem 2010; 53:8468-8484.
MA-4
JAK=Janus Kinase; TNF=Tumor Necrosis Factor
Author: Nancy McKay
Ready for QC
RevieIwn QedC
Source: QQCC CCoommpplleettee
In RE-QC
Date
Cumulative: Safety Data XELJANZ® (tofacitinib) Development Program 0310 AJuulgy 22001177
2051 J uAluy g20 17
Table–T. Jones; 9 years
2017
exposure: Mike Corbo
and Clinical Experience
Post Marketing: Andrea
Shapiro – as of 6 May
2016; To be updated.
PsA Safety: SCS  Xeljanz studied extensively with Phase 3 clinical development programs
– Including rheumatoid arthritis, psoriasis, psoriatic arthritis, and
ulcerative colitis

 Cumulatively, 22,132 patients have participated in the tofacitinib clinical
development program with patients exposed for up to 9 years

 The total estimated post-marketing exposure is in excess of 83,000
patient-years (PY)

 The safety of tofacitinib for the treatment of PsA is based on a clinical
development program that consists of
– 783 PsA patients that have been exposed to tofacitinib
– 775 patient-years of tofacitinib exposure as of May 10, 2016
MA-5
Ready for QC
ReviIenw QeCd
QC CoDmatep l ete
302 5J uJulyly 22001177
Author: Nancy McKay
Source: PEARL researched by
Sheila Santos and Gary Perry XELJANZ® (tofacitinib) Regulatory History
 Rheumatoid Arthritis (RA)
– Adult RA 5 mg BID IR NDA Approved – November 6, 2012
– Adult RA 11 mg QD XR NDA Approved – February 23, 2016

– Tofacitinib tablets are approved for RA in more than 80 countries;
including US, Canada, EU countries and Japan

 Other Indications
– PsO sNDA CRL – October 9, 2015 / sNDA Withdrawn – July 26, 2016
– PsA sNDAs (IR and XR) Submitted – February 22, 2017
– UC sNDA Submitted – May 4, 2017

BID=twice daily; CRL=Complete Response Letter; IR=Immediate Release; mg=milligram; NDA=New Drug Application;
MA-6
PsO=Psoriasis; QD=once daily; sNDA=supplemental New Drug Application; UC=Ulcerative Colitis; XR=Extended Release
Author: Nancy McKay
Source:
Ready for QC
ReviIenw QeCd
QC CoDmatep l ete
302 5J uJulyly 22001177
Tofacitinib for the Treatment of PsA
 5 mg BID of tofacitinib in PsA has shown efficacy consistent with
bDMARDs in TNFi-naïve patients, while also demonstrating similar
efficacy in TNFi-Inadequate Responders (IR)
 The safety profile of tofacitinib, including that in PsA patients, is well
characterized, stable and manageable. It is informed by a large and
growing safety database, with consistency between real world and
clinical safety data
 The benefit:risk profile of tofacitinib 5 mg BID for PsA is positive and is
based on substantial clinical evidence
MA-7
bDMARD=biologic Disease-Modifying Anti-Rheumatic Drug; TNFi=Tumor Necrosis Factor inhibitor
Author: Nancy McKay
Ready for QC
ReviIenw QeCd
Source: Proposed USPI
QC CoDmatep l ete
XELJANZ® (tofacitinib) for PsA
302 5J uJulyly 22001177
Proposed USPI: Indication and Dosage
Proposed Indication in sNDA
(1. INDICATIONS AND USAGE)
XELJANZ is indicated for the treatment of
adult patients with active psoriatic arthritis
Proposed Dosage in sNDA
(2. DOSAGE AND ADMINISTRATION)
The recommended dose of XELJANZ is 5 mg
twice daily used in combination with
conventional synthetic DMARDs
MA-8
USPI=United States Package Insert
Author: Nancy McKay
Source: RReeavInide yQw fCeo dr QC
QC Complete
26 July
30 July 2017
2017
Overview of Presentation
Topic Presenter
Nancy McKay
Introduction Director, Regulatory Affairs
Pfizer Inc
Philip Mease, MD, MACR
Psoriatic Arthritis:
Director, Rheumatology Research, Swedish-Providence-St.
A Physician’s Perspective/ Joseph Health Systems
Unmet Medical Need Clinical Professor, University of Washington School of Medicine,
Seattle, WA
Keith Kanik, MD, FACR
Tofacitinib PsA Development
Senior Director, Global Clinical Lead PsA
Program and Efficacy Inflammation and Immunology
Pfizer Inc
Daniela Graham, MD
Clinician, PsA Development Program
Tofacitinib PsA Safety
Inflammation and Immunology
Pfizer Inc
Thomas Jones, MD
Risk Management Senior Director, Safety Risk Management
Pfizer Inc
Michael Corbo, PhD
Senior VP, Chief Development Officer
Benefit:Risk and Conclusions
Inflammation and Immunology
Pfizer Inc
MA-9
Author: Thijs Hendriks
Ready for QC
Source: SME, see author QRCe vCIinoe wmQepCdl e te
27 July
31 July 2017
2017
Psoriatic Arthritis:
A Physician’s Perspective/
Unmet Medical Need
Philip Mease, MD, MACR
Director, Rheumatology Research, Swedish-Providence-St. Joseph
Health Systems
Clinical Professor of Medicine, University of Washington School of
Medicine, Seattle, WA
MA-10