PF-04965842 (abrocitinib) inhibits JAK1.1-3

Blocking JAK1 can have an effect on multiple cytokines, believed to be important drivers in the pathophysiology of atopic dermatitis.1

JAKs are responsible for producing a signal to initiate a cascade that ultimately affects IL-4– and IL-13–responsive genes, which are associated with reduced keratinocyte differentiation, Th2 cell differentiation, and IgE class switching.4,5

Inhibition of this pathway is thought to modulate cytokines, including IL-4, IL-13, IL-31, and IFNγ, which may be key signals in the atopic dermatitis pathway.1

PF-04965842 (abrocitinib) is a once-daily oral JAK1 inhibitor under investigation in subjects with moderate to severe atopic dermatitis.20-23

aBreakthrough Therapy designation is defined as a drug under investigation with preliminary clinical evidence that indicates the drug may demonstrate substantial improvement over
existing therapies on one or more clinically significant endpoints.1

JAK PATHWAY

JAK inhibition may be a factor in a number of inflammatory diseases, including alopecia areata,
atopic dermatitis, Crohn's disease, non-segmental vitiligo, plaque psoriasis, psoriatic arthritis,
rheumatoid arthritis, systemic lupus erythematosus, and ulcerative colitis.5-15

Figure adapted from Paller AS et al. J Allergy Clin Immunol. 2017;140(3):633-643.

  • Chronic idiopathic inflammatory diseases of the skin and gut are characterized by a hyperactive immune milieu containing upregulated chemokines, proinflammatory cytokines, and infiltration of an assortment of innate and adaptive immune cells5,16-19
  • The Janus kinase-signal transducer and activator of transcription (JAK-STAT) is a signaling pathway by which a number of proinflammatory cytokines (eg, IL-4, IL-13) may transduce their pathophysiologic functions and contribute to immune hyperactivity5,16
  • The binding of a cytokine to its receptor leads to JAK activation, which in turn phosphorylates STATs. STATs then dimerize and translocate to the nucleus, where they may direct expression of a number of genes affecting differentiation of immune cells and lead to upregulated cytokines5,16

EXTENSION STUDY IN ATOPIC DERMATITIS

For adults and adolescents with moderate to severe atopic dermatitis
who completed a qualifying phase 3 study20

PF-04965842 (abrocitinib) is an investigational small molecule that inhibits JAK1 with FDA Breakthrough Therapya designation for atopic dermatitis.1-3

Inhibition of the JAK1 pathway is thought to modulate cytokines, including IL-4, IL-13, IL-31, and IFNy, which may be key signals in the atopic dermatitis pathway.1,5

This is a phase 3, randomized, double-blind, long-term extension trial investigating the efficacy and safety of PF-04965842, with or without topical medications, administered to subjects aged 12 years and older with moderate to severe atopic dermatitis who completed a qualifying phase 3 study.20

Planned countries for recruitment include: Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czech Republic, Germany, Hungary, Israel, Italy, Japan, Latvia, Mexico, Netherlands, Poland, Romania, Russia, Serbia, Slovakia, South Korea, Spain, Taiwan, United Kingdom, and the United States.20

aBreakthrough designation is defined as a drug under investigation with preliminary clinical evidence that indicates the drug may demonstrate
substantial improvement over existing therapies on one or more clinically significant endpoints.1

VIEW STUDY DESIGN OF JADE EXTEND20

VIEW ENDPOINTS OF JADE EXTEND

PRIMARY ENDPOINTS20

  • Incidence of treatment-emergent adverse events up to 96 weeks
  • Incidence of serious adverse events and adverse events leading to discontinuation up to 96 weeks
  • Change from baseline in clinical laboratory values up to 96 weeks
  • Change from baseline in electrocardiogram measurements up to 96 weeks
  • Change from baseline in vital signs up to 96 weeks

KEY SELECTED SECONDARY ENDPOINTS20

  • Percentage of subjects achieving Investigator’s Global Assessment (IGA) score of clear (0) or almost clear (1) (on a 5-point scale) and a reduction from baseline of ≥2 points through week 96 at all scheduled time points
  • Percentage of subjects achieving greater than or equal to 50%, 75%, and 90% improvement from baseline on Eczema Area and Severity Index (EASI) total score through week 96 at all scheduled time points
  • Change from baseline in the percentage body surface area (BSA) affected through week 96 at all scheduled time points
  • Change from baseline in DLQI or CDLQI at all scheduled time points
  • Change from baseline in HADS at all scheduled time points

VIEW ELIGIBILITY CRITERIA OF JADE EXTEND

KEY SELECTED INCLUSION CRITERIA20

  • 12 years of age and older at the time of informed consent with a minimum body weight of 40 kg
  • Must have completed the full treatment period of a qualifying phase 3 study OR must have completed the full rescue treatment period of a qualifying phase 3 study (if applicable)
  • Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

KEY SELECTED EXCLUSION CRITERIA20

  • Other non-atopic dermatitis inflammatory skin diseases or conditions affecting skin
  • Discontinued treatment (or rescue treatment period) early in a qualifying phase 3 study OR triggered discontinuation criteria during the qualifying phase 3 study OR meets exclusion criteria of the qualifying phase 3 study
  • Ongoing adverse event in the qualifying phase 3 study, which in the opinion of the investigator or sponsor is an ongoing safety concern OR the subject is currently triggering safety monitoring criteria in the qualifying phase 3 study

For more information, visit

NOW ENROLLING IN ATOPIC DERMATITIS

For adolescents with moderate to severe atopic dermatitis21

PF-04965842 (abrocitinib) is an investigational small molecule that inhibits JAK1 with FDA Breakthrough Therapya designation for atopic dermatitis.1-3

Inhibition of the JAK1 pathway is thought to modulate cytokines, including IL-4, IL-13, IL-31, and IFNy, which may be key signals in the atopic dermatitis pathway.1,5

This is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial to investigate the efficacy and safety of PF-04965842 co-administered with background medicated topical therapy in subjects aged 12 to 17 years who have moderate to severe atopic dermatitis. The efficacy and safety of 2 dosage strengths of PF-04965842, 100 mg and 200 mg, taken once daily will be evaluated relative to placebo over 12 weeks, with background therapy applied twice daily for the duration of the treatment period.21

Planned countries for recruitment include: Australia, China, Czech Republic, Hungary, Japan, Latvia, and the United States.21

aBreakthrough designation is defined as a drug under investigation with preliminary clinical evidence that indicates the drug may demonstrate
substantial improvement over existing therapies on one or more clinically significant endpoints.1

VIEW STUDY DESIGN OF JADE TEEN21

VIEW ENDPOINTS OF JADE TEEN

PRIMARY ENDPOINTS21

  • Percentage of subjects achieving an Investigator's Global Assessment (IGA) score of clear (0) or almost clear (1) (on a 5-point scale) and a reduction from baseline of ≥2 points at week 12
  • Percentage of subjects achieving a ≥75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) at week 12

KEY SELECTED SECONDARY ENDPOINTS21

  • Percentage of subjects achieving a ≥4-point improvement in pruritus from baseline on the Numeric Rating Scale (NRS) at days 2-14 and weeks 2, 4, 8, 12 (or time of early termination), and 16
  • Change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) total score at week 12 or the time of early termination
  • Time to achieve a ≥4-point improvement in pruritus from baseline on the NRS at days 2-15
  • Percentage of subjects achieving a ≥75% improvement from baseline on the EASI-75 at weeks 2, 4, 8, and 16
  • Percentage of subjects achieving an IGA score of clear or almost clear and a reduction from baseline of ≥2 points at weeks 2, 4, 8, and 16

VIEW ELIGIBILITY CRITERIA OF JADE TEEN

KEY SELECTED INCLUSION CRITERIA21

  • 12 to 17 years of age with a minimum body weight of 40 kg
  • Diagnosis of atopic dermatitis for at least 1 year and current status of moderate to severe disease (≥ the following scores: body surface area (BSA) 10%, IGA 3, EASI 16, Pruritus NRS 4)

KEY SELECTED EXCLUSION CRITERIA21

  • Acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation
  • Unwilling to discontinue current atopic dermatitis medications prior to the study or require treatment with prohibited medications during the study
  • Prior treatment with JAK inhibitors
  • Other active non-atopic dermatitis inflammatory skin diseases or conditions affecting skin

For more information, visit

NOW ENROLLING IN ATOPIC DERMATITIS

For adults with moderate to severe atopic dermatitis
on background topical therapy22

PF-04965842 (abrocitinib) is an investigational small molecule that inhibits JAK1 with FDA Breakthrough Therapya designation for atopic dermatitis.1-3

Inhibition of the JAK1 pathway is thought to modulate cytokines, including IL-4, IL-13, IL-31, and IFNy, which may be key signals in the atopic dermatitis pathway.1,5

This is a phase 3, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study investigating the efficacy and safety of PF-04965842 and dupilumab in comparison with those of placebo in adult subjects with moderate to severe atopic dermatitis on background topical therapy.22

Planned countries for recruitment include: Australia, Bulgaria, Canada, Chile, Czech Republic, France, Germany, Hungary, Italy, Japan, Latvia, Mexico, Poland, Slovakia, South Korea, Spain, Taiwan, the United Kingdom, and the United States.22

aBreakthrough designation is defined as a drug under investigation with preliminary clinical evidence that indicates the drug may demonstrate
substantial improvement over existing therapies on one or more clinically significant endpoints.1

VIEW STUDY DESIGN OF JADE COMPARE22

VIEW ENDPOINTS OF JADE COMPARE

PRIMARY ENDPOINTS22

  • Percentage of subjects achieving an Investigator's Global Assessment (IGA) score of clear (0) or almost clear (1) (on a 5-point scale) and a reduction from baseline of ≥2 points at week 12
  • Percentage of subjects achieving a ≥75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) at week 12

KEY SELECTED SECONDARY ENDPOINTS22

  • Percentage of subjects achieving a ≥4-point improvement in pruritus from baseline on the Numeric Rating Scale (NRS) at all scheduled time points through week 24
  • Percentage of subjects achieving an IGA score of clear or almost clear and a reduction from baseline of ≥2 points at all scheduled time points, excluding week 12, through week 24
  • Percentage of subjects achieving a ≥75% improvement from baseline on the EASI-75 at all scheduled time points, excluding week 12, through week 24
  • Percentage of subjects achieving a ≥50%, ≥90%, and 100% improvement from baseline on the EASI-50, EASI-95, and EASI-100 at all scheduled time points through week 24
  • Time to achieve a ≥4-point improvement in pruritus from baseline on the NRS

VIEW ELIGIBILITY CRITERIA OF JADE COMPARE

KEY SELECTED INCLUSION CRITERIA22

  • 18 years of age or older at the time of informed consent
  • Diagnosis of atopic dermatitis for at least 1 year and current status of moderate to severe disease (≥ the following scores: body surface area (BSA) 10%, IGA 3, EASI 16, Pruritus NRS 4)
  • Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with medicated topical therapy for atopic dermatitis for at least 4 weeks or who have required systemic therapies for disease control
  • If receiving concomitant medications for any reason other than atopic dermatitis, must be on a stable regimen prior to day 1 and through the duration of the study

KEY SELECTED EXCLUSION CRITERIA22

  • Unwilling to discontinue current atopic dermatitis medications prior to the study or require treatment with prohibited medications during the study
  • Other active non-atopic dermatitis inflammatory skin diseases or conditions affecting skin
  • Prior treatment with JAK inhibitors
  • Previous treatment with dupilumab

For more information, visit

NOW ENROLLING IN ATOPIC DERMATITIS

For adults and adolescents with moderate to severe atopic dermatitis22

PF-04965842 (abrocitinib) is an investigational small molecule that inhibits JAK1 with FDA Breakthrough Therapya designation for atopic dermatitis.1-3

Inhibition of the JAK1 pathway is thought to modulate cytokines, including IL-4, IL-13, IL-31, and IFNy, which may be key signals in the atopic dermatitis pathway.1,5

This is a phase 3, randomized withdrawal, double-blind, placebo-controlled, multicenter study investigating the efficacy and safety of PF-04965842 in subjects aged 12 years and older with moderate to severe atopic dermatitis with the option of rescue treatment in flaring subjects.23

Planned countries for recruitment include: Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, China, Germany, Israel, Italy, Latvia, Mexico, Netherlands, Poland, Romania, Russia, Serbia, Slovakia, Spain, Taiwan, and the United States.23

aBreakthrough designation is defined as a drug under investigation with preliminary clinical evidence that indicates the drug may demonstrate
substantial improvement over existing therapies on one or more clinically significant endpoints.1

VIEW STUDY DESIGN OF JADE REGIMEN

VIEW ENDPOINTS OF JADE REGIMEN

PRIMARY ENDPOINTS23

  • Loss of response, denoted as flare and defined as a loss of ≥50% of the Eczema Area and Severity Index (EASI) response at week 12 and an Investigator’s Global Assessment (IGA) score of ≥2, requiring rescue treatment during the blinded treatment period

KEY SELECTED SECONDARY ENDPOINTS23

  • IGA score at all scheduled time points
  • EASI total score at all scheduled time points
  • Percentage of subjects achieving achieving a ≥4-point improvement in pruritus from baseline on the Numeric Rating Scale (NRS) at all scheduled time points
  • Change from relevant baseline in percent body surface area (BSA) at all scheduled time points
  • Proportion of subjects achieving a ≥50% and ≥75% improvement in SCORing Atopic Dermatitis (SCORAD) subjective assessments (SCORAD-50 and SCORAD-75) from relevant baseline at all scheduled time points

VIEW ELIGIBILITY CRITERIA OF JADE REGIMEN

KEY SELECTED INCLUSION CRITERIA23

  • 12 years of age or older with a minimum body weight of 40 kg
  • Diagnosis of atopic dermatitis for at least 1 year and current status of moderate to severe disease (≥ the following scores: BSA 10%, IGA 3, EASI 16, Pruritus NRS 4)
  • Recent history of inadequate response or inability to tolerate topical atopic dermatitis treatments or require systemic treatments for atopic dermatitis control

KEY SELECTED EXCLUSION CRITERIA23

  • Unwilling to discontinue current atopic dermatitis medications prior to the study or require treatment with prohibited medications during the study
  • Prior treatment with JAK inhibitors
  • Other active non-atopic dermatitis inflammatory skin diseases or conditions affecting skin

For more information, visit