Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Abrocitinib
PF-04965842 · 17 trials · 15 indications
The difference in percentage of responders based on vIGA at Week 12 in participants with moderate-to-severe AD treated with abrocitinib versus placebo.
The difference in percentage of responders based on EASI-75 at Week 12 in participants with moderate-to-severe AD treated with abrocitinib versus placebo
The number of the treatment emergent adverse events, serious adverse events and adverse events leading to discontinuation among patients with moderate-to-severe disease treated with abrocitinib regardless of discontinuation from study treatment.
The difference in proportion of responders based on EASI-75 at Week 12 in patients with moderate-to-severe AD treated with abrocitinib versus placebo
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic or other situations where medical or scientific judgement should be exercised by investigator. AEs included SAEs and all non-SAEs.
The severity of itch (pruritus) due to atopic dermatitis (AD) was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
EASI quantifies severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.
The IGA of Atopic Dermatitis (AD) was scored on a 5-point scale (0-4), reflecting a global consideration of the erythema, induration and scaling. The overall severity of AD was assessed according to the 5-point scale: 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, and 4=Severe. Participants who withdrew from the study were counted as non-responder.
The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD. Participants who withdrew from the study were counted as non-responder.
IGA assessed severity of atopic dermatitis (AD) on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded scalp, palms and sole.
EASI evaluates severity of participants with AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
IGA assesses severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded soles, palms and scalp.
EASI evaluates severity of participants AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\] and lower limbs \[including buttocks\] on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
Percentage of participants with loss of response requiring rescue treatment during double blind period was determined. Loss of response denoted as flare and was define as a loss of at least 50% of EASI total score at Week 12 and with an IGA score of 2 or higher. EASI quantifies severity of participant's atopic dermatitis (AD) based on both severity of lesion clinical signs and % of body surface area (BSA) affected. EASI is a composite scoring by AD clinical evaluator of degree of erythema, induration/papulation, excoriation, and lichenification for each of 4 body regions. EASI total score range from 0.0 to 72.0, with higher scores representing greater severity of AD. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores = more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate and 4 = severe.
Time (in days) to loss of response based on achieving IGA \>=2 was measured from date of first dose of randomized treatment until last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) and based on EASI, loss of at least 50% of EASI response at Week 12 and IGA score of 2 or higher. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores=more severity), reflecting global consideration of erythema, induration and scaling with scores 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. EASI composite score evaluates degree of erythema, induration/papulation, excoriation, and lichenification.
The incidence of treatment emergent adverse events
The incidence of serious adverse events and adverse events leading to discontinuation
IGA assesses severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded sole, palms and scalp.
EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
The percentage body surface area (BSA) involvement by GA after 6 months of treatment with abrocitinib 200 mg daily in 10 patients with moderate to severe GA affecting at least 5% body surface area (BSA).
Improvement in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) after 6 months of abrocitinib therapy. CSAMI is a validated clinical scoring tool for cutaneous sarcoidosis activity and severity. Scores range from 0 to 165. Higher score is worse.
Mean fold-changes from baseline at Week 12 in the biomarkers for general inflammation (Matrix Metallopeptidase \[MMP\]12), hyperplasia (Keratin \[KRT\]16), Th2 immune response (C-C motif chemokine ligand \[CCL\]17, CCL18, CCL26), and Th22 immune response (S100 calcium binding protein A \[S100A\]8, S100A9, S100A12), in lesional (LS) and non-lesional (NL) skin tissues, respectively. Expression levels from RT-PCR are normalized to the housekeeping gene RPLP0 by negatively transforming the Ct values to -dCt.
The IGA score quantifies the severity of participants' atopic dermatitis (AD). Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate and severe, respectively).
Maximum observed plasma PF-04965842 concentration.
Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time.
Maximum observed plasma concentration for active metabolite, PF-06471658 (M1).
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1).
Maximum observed plasma concentration for active metabolite, PF-07055087 (M2).
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2).
AUCinf is area under the concentration-time curve (AUC) from time 0 (pre-dose) extrapolated to infinite time.
| Arm | Type | Description |
|---|---|---|
| Abrocitinib | EXPERIMENTAL | Participants will receive liquid oral suspension of Abrocitinib. |
| Matching Placebo | PLACEBO_COMPARATOR | Participants will receive liquid oral suspension of matching placebo. |
| Extension | EXPERIMENTAL | Patients who have completed other abrocitinib studies |
| De novo | EXPERIMENTAL | Patients who have not participated other abrocitinib studies |
| Abrocitinib 100 mg | EXPERIMENTAL | Participants will receive abrocitinib 100 mg by mouth (QD). |
| Abrocitinib 200 mg | EXPERIMENTAL | Participants will receive abrocitinib 200 mg QD. |
| Abrocitinib 200 mg plus placebo injection | EXPERIMENTAL | Abrocitinib 200 mg daily through Week 26, plus placebo injections every other week through Week 24 |
| Dupilumab 300 mg plus placebo tablets | ACTIVE_COMPARATOR | Dupilumab 300 mg every other week (2 injections on Day 1) through Week 24, plus placebo tablets daily through Week 26 |
| Placebo | PLACEBO_COMPARATOR | Placebo |
| PF-04965842 100 mg QD | EXPERIMENTAL | active |
| PF-04965842 200 mg QD | EXPERIMENTAL | active |
| PF-04965842 100 mg + Placebo Inj followed by PF-04965842 100mg | EXPERIMENTAL | Once-daily oral PF-04965842 100 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 100 mg from Week 16 to Week 20 |
| PF-04965842 200 mg + Placebo Inj followed by PF-04965842 200mg | EXPERIMENTAL | Once-daily oral PF-04965842 200 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 200 mg from Week 16 to Week 20 |
| Dupilumab Injection + Oral Placebo followed by Oral Placebo | ACTIVE_COMPARATOR | Dupilumab injected subcutaneously once every 2 weeks + once-daily oral Placebo from Day 1 until Week 16 followed by once-daily oral Placebo from Week 16 to Week 20 |
| Oral Placebo + Placebo Inj followed by 100 mg PF-04965842 | PLACEBO_COMPARATOR | Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 100 mg PF-04965842 from Week 16 to Week 20 |
| Oral Placebo + Placebo Inj followed by 200 mg PF-04965842 | PLACEBO_COMPARATOR | Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 200 mg PF-04965842 from Week 16 to Week 20 |
| PF-04965842 100 mg | EXPERIMENTAL | - |
| PF-04965842 200 mg | EXPERIMENTAL | - |
| Placebo QD | PLACEBO_COMPARATOR | Double-blind randomized treatment following open label run-in period. |
| Abrocitinib 200 mg daily | EXPERIMENTAL | 6 months of treatment with abrocitinib 200 mg daily |
| Cohort 1 | EXPERIMENTAL | 10 mg of PF-04965842 QD |
| Cohort 2 | EXPERIMENTAL | 30 mg of PF-04965842 QD |
| Cohort 3 | EXPERIMENTAL | 100 mg of PF-04965842 QD |
| Cohort 4 | EXPERIMENTAL | 200 mg of PF-04965842 QD |
| Cohort 5 | PLACEBO_COMPARATOR | placebo QD |
| PF-04965842 | EXPERIMENTAL | PF 04965842 is an oral selevtive janus kinase (JAK) 1 inhibitor |
| Name | Type | Description |
|---|---|---|
| Abrocitinib | DRUG | Administered orally |
| Placebo | DRUG | Administered orally |
| Abrocitinib 100 mg | DRUG | Orally administered, abrocitinib 100 mg tablets QD |
| Abrocitinib 200 mg | DRUG | Orally administered, abrocitinib 200 mg tablets QD. |
| Dupilumab 300 mg | COMBINATION_PRODUCT | Dupilumab 300 mg administered as a single subcutaneous injection every other week for 24 weeks (2 injections on day 1). Placebo tablets will be administered daily. |
| PF-04965842 | DRUG | 100 mg QD |
| PF04965842 | DRUG | 200 mg QD |
| PF-04965842 100 mg | DRUG | PF-04965842 100 mg, administered as two tablets to be taken orally once daily as follows: 1. In the arm "PF-04965842 100 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 100 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20; 2. In the arm "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" subjects take PF-04965842 100 mg from Week 16 to Week 20. |
| PF-04965842 200 mg | DRUG | PF-04965842 200 mg, administered as two tablets to be taken orally once daily as follows: 1. In the arm "PF-04965842 200 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 200 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20; 2. In the arm "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842" subjects take PF-04965842 200 mg from Week 16 to Week 20. |
| Dupilumab | DRUG | Two subcutaneous injections of Dupilumab 300 mg as a loading dose administered on Day 1 (for a total of 600 mg) followed by one injection once every two weeks (q2w) until Week 16. |
| Oral Placebo | DRUG | Oral placebo (for PF-04965842) administered as two tablets to be taken orally once daily as follows: 1. In the arm "Dupilumab Injection + Oral Placebo followed by Oral Placebo," the Oral Placebo is taken together with Dupilumab from Day 1 until Week 16, then by itself to Week 20; 2. In the arms "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" and "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842," subjects, take Oral Placebo from Day 1 until Week 16. |
| Injectable Placebo | DRUG | Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16. |
Inclusion Criteria: • Children aged 2 to \<6 years at the time of informed consent /assent. Disease Characteristics: * All participants must meet all of the following criteria: * A documented diagnosis of chronic AD for at least 1 year prior to screening and confirmed at screening and baseline vi...
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PF-04965842 is an investigational oral small molecule being developed for moderate-to-severe atopic dermatitis, a form of eczema. It has also been studied in dermatitis, hepatic impairment, and renal impairment. It is not yet approved and remains in clinical development.
PF-04965842 targets JAK1, a kinase enzyme involved in inflammatory signaling. By inhibiting JAK1, the drug is designed to reduce the immune pathways that drive atopic dermatitis. JAK1 belongs to the Janus kinase family of kinases.
PF-04965842 is being developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. Pfizer is the sponsor of the clinical program evaluating the drug in atopic dermatitis and related conditions.
PF-04965842 is in Phase 3 clinical development. Five trials have been completed, including Phase 1, Phase 2, and Phase 3 studies, with no active trials currently listed. The drug is investigational and has not been approved by the FDA.
Completed trials include NCT03915496, a Phase 2 mechanism-of-action study in atopic dermatitis; NCT03796676, a Phase 3 study in adolescents with atopic dermatitis; NCT03720470, a Phase 3 study comparing PF-04965842 with dupilumab in adults; and NCT03660241, a Phase 1 renal impairment study.