Moderate to Severe Plaque Psoriasis Efficacy

Study Design

The US Psoriasis Pivotal Trial was a two-part, multicenter, phase 3 study consisting of a 24-week double-blind period followed by a 60-week withdrawal and retreatment period. A total of 652 patients with active but clinically stable plaque psoriasis involving at least 10% of body surface area (BSA) and a minimum Psoriasis Area and Severity Index (PASI) score of 10. Patients were randomized to receive ENBREL 50 mg twice weekly (BIW, n=164), ENBREL 25 mg BIW (n=162), ENBREL 25 mg weekly (QW, n=160), or placebo (n=166) for 12 weeks. After Week 12, patients in the placebo group began blinded treatment with ENBREL 25 mg BIW. ^1,2

At Week 24, patients with 50% PASI improvement from baseline discontinued ENBREL treatment until disease relapse (loss of the 50% PASI improvement that was obtained by Week 24). Upon relapse, patients resumed blinded ENBREL therapy at the same dose they had received from Weeks 13 to 24. ¹

A post hoc analysis was conducted for an open-label extension (OLE), including 439 patients from the US Psoriasis Pivotal Trial after completing a minimum of 60 weeks in the primary study. Patients in the OLE received ENBREL 50 mg QW for the first 12 weeks followed by a dose escalation of 50 mg BIW for patients with an inadequate clinical response. ^3,4

Additional Study Details and Study Schema

• Patients were limited to low- to moderate-strength topical corticosteroids in the axillary, groin, and scalp regions ²
• Primary endpoint: PASI 75 at Week 12 ²
• Select secondary endpoints: PASI 50, PASI 90, percent improvement from baseline PASI, static Physician's Global Assessment (sPGA) of clear or almost clear, and the patient’s global assessment of psoriasis at Weeks 12, 24, 48, and 72 ^2,3
• OLE primary endpoints: The incidence of adverse events, infectious episodes, serious adverse events, serious infectious episodes, injection site reactions, changes from baseline in laboratory values, and presence/absence of an antibody response ¹
• OLE select secondary endpoints: Percent PASI improvement relative to baseline in the parent study ¹

US Psoriasis Pivotal Trial ^2-4 (N=652)

mITT = modified intent-to-treat.

Selected Baseline Demographics ^1,5

Age (mean)	45 years
Male	67%
Caucasian	87%
Weight (mean)	208 lb (86-437 lb)
Body mass index (mean)	31
BSA involvement (mean)	29%
PsO duration (mean)	19 years
PASI (mean)	18

Primary Endpoint

• ~49% of patients achieved a PASI 75 score by Week 12 in the ENBREL 50 mg BIW group (n=164, LOCF) vs 4% with placebo (n=166)

Recapture Results Through 60 Weeks

• For the 50 mg BIW dosing, 91% of the initial change in mean PASI was regained 12 weeks after retreatment ³
• For the 25 mg BIW dosing, 99% of the initial change in mean PASI was regained 12 weeks after retreatment ³

Improvement in Mean PASI in the US Psoriasis Pivotal Trial ^3,6

* Patients who completed 12 weeks of retreatment. ¹

^† Only patients with ≥50% PASI improvement from baseline at Week 24 discontinued ENBREL treatment and were enrolled in this part of the study. ¹

^‡ Last observation carried forward (LOCF).

^§ As observed.

• The mean numerical difference for each patient (primary endpoint) between the PASI score at Week 12 of retreatment and the PASI score at Week 12 of initial treatment in the ENBREL 50 mg BIW group was -1.4 (±0.5) and in the ENBREL 25 mg BIW group was -0.3 (±0.5) ³

Recapture Results Through 132 Weeks

94% of the Week 24 response was recaptured at Week 60 ⁷

Mean % of PASI Improvement From the US Psoriasis Pivotal Trial and the OLE ^3,7

• The following patients were not included in this OLE efficacy analysis:
• Patients (n=37) in the ENBREL 50 mg BIW group after Week 12 during the US Psoriasis Pivotal Trial who were randomized to the 50 mg QW group through 72 weeks of the OLE ⁷
• Patients (n=284) who increased their ENBREL dose to 50 mg BIW after Week 12 during the OLE ⁸
• Patients (n=75) in the ENBREL 50 mg QW continuous arm through 72 weeks who had >30 days off treatment between the US Psoriasis Pivotal Trial and the OLE ⁹
• Patients (n=5) met 2 of these exclusion criteria: received ENBREL 50 mg BIW who had >30 days off treatment
• Patients included in the trial started with placebo, ENBREL 25 mg QW, ENBREL 25 mg BIW, and ENBREL 50 mg BIW for 12 weeks. After 12 weeks, placebo patients were switched to ENBREL 25 mg BIW ³
• OLE results are from post hoc analysis. These results are exploratory and no statistical conclusions can be drawn
• Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. A total of 20 patients (2.2%) had adverse events that led to discontinuation of the study ⁴

Study Design

The Global Psoriasis Pivotal Trial was a 48-week, multicenter, double-blind, randomized, phase 3 trial of 611 adult patients with active but clinically stable PsO involving at least 10% of BSA and a minimum PASI score of 10. 583 patients received at least one dose of study drug and these were the 583 patients included in the primary analysis. Patients were randomized to receive ENBREL 50 mg (n=194), ENBREL 25 mg (n=196), or placebo (n=193) BIW over 12 weeks. After Week 12, all patients (N=583) received open-label ENBREL 25 mg BIW over 36 weeks. Patients were limited to low- to moderate-strength topical corticosteroids in the axillary, groin, and scalp regions. A post hoc analysis was conducted for an OLE, including 473 patients from the Global Psoriasis Pivotal Trial after completing a minimum of 36 weeks of open-label treatment. Patients in the OLE received ENBREL 50 mg QW. ^4,10,11

Additional Study Details and Study Schema

• Primary endpoint: PASI 75 at Week 12 ¹⁰
• Select secondary endpoints: PASI 50, PASI 90, percent improvement from baseline PASI, sPGA of clear or almost clear, and the patient’s global assessment of psoriasis at Weeks 12, 24, and 48 ⁸
• OLE primary endpoints: The incidence of adverse events, infectious episodes, serious adverse events, serious infectious episodes, injection site reactions, changes from baseline in laboratory values, and presence/absence of an antibody response ³
• OLE select secondary endpoints: Percent PASI improvement relative to baseline in the parent study ³

Global Psoriasis Pivotal Trial ^4,10,11 (N=583)

Selected Baseline Demographics ^9,12

Age (median)	45 years
Male	66%
Caucasian	91%
Weight (mean)	194 lb
Body mass index (mean)	30
BSA involvement (mean)	28%
PsO duration (mean)	20 years
PASI (mean)	19

PASI Results at Week 12

• Primary endpoint: Nearly half (46%) of patients saw 75% skin clearance in their moderate to severe plaque PsO in 12 weeks with ENBREL in the 50 mg BIW group (n=203) vs 3% with placebo (n=204, primary endpoint; intent-to-treat nonresponder imputation [ITT NRI] analysis) ⁶
• 66% mean PASI improvement at Week 12 in the ENBREL 50 mg BIW group (n=194) vs 0.1% with placebo (n=193, mITT LOCF analysis) ¹³

PASI Results Through Week 120

Mean PASI Improvement (%) During the Global Psoriasis
Pivotal Trial and the OLE ^7,10

• The following patients were not included in the OLE efficacy analysis:
• Patients who increased their ENBREL dose to 50 mg BIW after Week 12 during the OLE (n=307) ⁸
• Patients in the ENBREL 50 mg QW continuous arm through 72 weeks who had >30 days of treatment between Global Psoriasis Pivotal Trial and the OLE ⁹
• Patients included in this trial started with placebo, ENBREL 25 mg BIW, or 50 mg BIW for 12 weeks. All patients received ENBREL 25 mg BIW after 12 weeks ¹⁰
• OLE results are from post hoc analysis. These results are exploratory and no statistical conclusions can be drawn
• Consider OLE study limitations when interpreting results. The OLE is not blinded, not controlled, and includes inherent self-selection bias. A total of 20 patients (2.2%) had adverse events that led to discontinuation of the study ⁴

Photos of Patients From the Global Psoriasis Pivotal Trial

• These photos depict only a select area of the patient’s skin involvement. Included below the photos are the patients’ actual PASI scores at baseline, Week 12, and Week 24 ^14,15

Study Design

The Phase 3 Study was a 12-week, randomized, double-blind, placebo-controlled, parallel-group study of 618 patients with active and clinically significant plaque psoriasis involving ≥10% BSA and a minimum PASI score of 10. Patients received ENBREL 50 mg BIW (n=311) or placebo BIW (n=307). ¹⁶

• Primary endpoint: PASI 75 at Week 12 ¹⁷
• Select secondary endpoints: Patient assessment of itching at Week 12, patient assessment of improvement from baseline in skin pain at Week 12, patient-reported outcomes of itching and improvement from baseline in skin pain at Week 12 ¹⁷
• The severity of skin pain and itch was assessed by patients based on a single-item questionnaire * rating it on a scale of 0 (none) to 10 (severe) for pain and 0 (none) to 5 (severe) for itch ¹⁷

* Subjects were asked to rate their skin pain and itch as a component of a psoriasis clinical trial, so it can be reasonably assumed that the subjects answered this question attributing the skin pain and itch to their moderate to severe plaque psoriasis.

Additional Study Details and Study Schema

Primary Endpoint Result

• 47% of patients achieved PASI 75 with ENBREL (mean baseline PASI=18.3) ¹⁶

Itch Scores

58% improvement from baseline in mean itch score ¹⁷

Itch Scores Reported by ENBREL Patients at Baseline and at Week 12 (LOCF) ¹⁷

Pain Scores

68% improvement in mean skin pain score relative to the mean baseline score ¹⁷

Improvement in Mean Skin Pain Score at Week 12 (LOCF) ¹⁷

PSSI Results

• 91% mean PSSI improvement at Week 24 ¹⁸

Mean Percent Improvement in PSSI Score at Weeks 12 and 24 in the ENBREL Scalp Involvement Study ¹⁸*

* ITT analysis with LOCF imputation.

^† P<0.0001 vs placebo.

• Among PSSI 75 achievers, the median time to PSSI 50 and PSSI 75 was approximately 4 weeks and approximately 8 weeks, respectively ²⁰

PASI Results

78% mean PASI improvement at Week 24 ¹⁹

Mean Percent Improvement in PASI Score at Weeks 12 and 24 in the ENBREL Scalp Involvement Study ^18,19*

* ITT analysis with LOCF imputation.

Photos of Patients in Scalp Involvement Study

• These are actual photos from ENBREL clinical trial patients and depict only a select area of the patients' scalp involvement. Included below the photos are the patients' actual PSSI scores at baseline, Week 12, and Week 24 ²¹

Scalp Itch Scores

Patients experienced less scalp itch with ENBREL

• The severity of scalp itch was assessed by patients based on a single-item questionnaire rating it on a scale of 0 (none) to 5 (severe) ¹⁹
• Scalp itch was assessed as an exploratory endpoint in this study and no statistical conclusions can be drawn ¹⁹

Improvement in Mean Itch Score Through Week 24 ¹⁹*^†

* Subjects were asked to rate their scalp itch as a component of a psoriasis clinical trial, so it can be reasonably assumed that the subjects answered this question attributing the scalp itch to their moderate to severe plaque psoriasis.

^† ITT analysis with LOCF imputation.

Scalp Pain Scores

Patients experienced less scalp pain with ENBREL

• The severity of scalp pain was assessed by patients on a scale of 0 (none) to 10 (severe) ¹⁹
• Scalp pain was assessed as an exploratory endpoint in this study and no statistical conclusions can be drawn ¹⁹

Improvement in Mean Pain Score Through Week 24 ¹⁹*^†

* Subjects were asked to rate their scalp pain as a component of a psoriasis clinical trial, so it can be reasonably assumed that the subjects answered this question attributing the scalp pain to their moderate to severe plaque psoriasis.

^† ITT analysis with LOCF imputation.

Primary Endpoint and Additional Efficacy Results

• Primary endpoint: 57% of patients achieved PASI 75 with ENBREL vs 11% with placebo (P<0.001) at Week 12 ²⁴
• 52% of patients treated with ENBREL had an sPGA of clear or almost clear vs 13% of patients treated with placebo at Week 12 ⁶
• Prespecified exploratory endpoint: 69% mean PASI improvement with ENBREL vs 32% with placebo at Week 12 ²⁸
• OLE primary endpoint: Long-term safety profile for up to 264 additional weeks was assessed in an open-label extension study; no new safety signals were identified ⁶

PASI Results Through 36 Weeks

• 23%, 11%, and 7% of patients treated with placebo achieved PASI 50, PASI 75, and PASI 90, respectively, at 12 weeks (n=105) ²⁸
• 86%, 65%, and 38% of patients who switched from placebo to ENBREL achieved PASI 50, PASI 75, and PASI 90, respectively, at 36 weeks (Weeks 0-12: n=105; Weeks 16-36: n=103) ²⁴

* Open-label period or incomplete-responder arm; patients could enter the incomplete-responder arm at Week 24 or Week 36.

^† ITT NRI analysis.

PASI Results Through 312 Weeks

Results through 312 weeks in the combined primary study and open-label extension

* Patients were treated and evaluated for 5 years or until they turned 18, whichever came last. Seven patients discontinued due to disease progression (3.8%). ²⁹

Consider OLE study limitations when interpreting the above results. The OLE study is not blinded, not controlled, and includes inherent self-selection bias. A total of 6 patients (3.3%) had adverse events that led to discontinuation of ENBREL and 5 patients (2.7%) had adverse events that led to discontinuation of the study. ²⁸

sPGA Results Through 36 Weeks

• Approximately half of pediatric ENBREL patients were clear or almost clear at 12 through 36 weeks ²⁴

* ENBREL: n=106 through Week 12 and n=105 through Week 36. Placebo/ENBREL: n=105 through Week 12 and n=103 through Week 36.

52% of patients were clear or almost clear with ENBREL vs 13% with placebo at 12 weeks ⁶

sPGA Results Through 312 Weeks

Results through 312 weeks in the combined primary study and open-label extension

• ~4 out of 10 patients treated with ENBREL consistently experienced clear or almost clear skin through 312 weeks ³⁰*

Consider OLE study limitations when interpreting the above results. The OLE study is not blinded, not controlled, and includes inherent self-selection bias. A total of 6 patients (3.3%) had adverse events that led to discontinuation of ENBREL and 5 patients (2.7%) had adverse events that led to discontinuation of the study. ²⁸

Results by BMI Post Hoc Analysis

* Healthy weight = body mass index (BMI) 5th-84th percentile; overweight = BMI 85th-94th percentile; obese = BMI ≥95th percentile. ³²

• Post hoc analysis is exploratory and no statistical conclusions can be drawn