raptiva tm (efalizumab) efficacy
DESCRIPTION
Raptiva TM (efalizumab) Efficacy. Lee Kaiser, PhD Director Clinical Biostatistics Genentech, Inc. Phase III Studies. Conclusions About Raptiva Efficacy. Significant efficacy at Week 12 Onset of efficacy by Week 4 Psoriasis returns when Raptiva stopped Significant efficacy on retreatment - PowerPoint PPT PresentationTRANSCRIPT
1C-EFF-
RaptivaTM (efalizumab) Efficacy
Lee Kaiser, PhD
DirectorClinical Biostatistics
Genentech, Inc.
2C-EFF-
Phase III Studies
StudyNumber Study Design
Number ofPatients
Randomized
2390 Placebo-controlled Double-blind Randomized 556
2600 Placebo-controlled Double-blind Randomized 686
2058 Placebo-controlled Double-blind Randomized 498
2059 Placebo-controlled Double-blind Randomized 597
3C-EFF-
Conclusions About Raptiva Efficacy
• Significant efficacy at Week 12
• Onset of efficacy by Week 4
• Psoriasis returns when Raptiva stopped
• Significant efficacy on retreatment
• Efficacy improves with continuous treatment past 12 weeks
4C-EFF-
Study 2390:Pivotal Phase III Efficacy Study
RandomizationDay 0
Screen
Primary AnalysisWeek 12 (Day 84)
Placebo (n = 187)
Raptiva 1 mg/kg (n = 369)
Entrance criteria• Plaque psoriasis ≥ 6 months• BSA ≥ 10%• PASI ≥ 12• Candidate for, or history of, systemic therapy
5C-EFF-
Study 2390: Primary Efficacy Variable, the Psoriasis Area and Severity Index
• Physician-performed assessment • Extent of psoriasis and the degree of plaque
erythema, thickness, and scaling• Index ranges from 0 to 72, higher scores worse
Primary analysis based on rate of PASI-75 response
• PASI-75 responder: A patient with a PASI percent improvement from baseline of ≥ 75%
• PASI-75 nonresponder: A patient with a PASI percent improvement from baseline of < 75%
6C-EFF-
Study 2390: Secondary Efficacy Endpoints
• Physician-derived assessments– PASI-50– PASI % improvement from baseline– Physician’s Global Assessments as given in
briefing book• Patient-reported assessments
– DLQI: Dermatology Life Quality Index• 10 items, each rated 0=Not at All, 1=A Little,
2=A Lot, 3=Very Much, or Not Relevant – Others as given in briefing book
7C-EFF-
Placebo(n = 187)
Raptiva 1 mg/kg(n = 369)
Age, mean (range), yr 45 (20-75) 45 (18-75)
≥ 65 yrs 7% 6%
Sex Male 71% 68%Female 29% 32%
Race White 89% 90%
Nonwhite 11% 10%
Study 2390: Demographics
8C-EFF-
Placebo(n = 187)
Raptiva 1 mg/kg(n = 369)
Duration of psoriasis, mean sd, yr 19 11 19 12
History of systemic therapy 59% 60%
Baseline PASI, mean sd 19 7 19 8
Baseline BSA, mean sd, % 27 16 28 17
Study 2390: Baseline Characteristics
9C-EFF-
4
27
0
5
10
15
20
25
30
35Placebo Raptiva 1 mg/kg
% o
f pat
ient
s w
ith P
AS
I-75
Study 2390
*
n = 187 n = 369
Significant Effect on the Primary Endpoint:Rate of PASI-75 at Week 12
* Fisher’s exact test, Raptiva vs. placebo, ITT analysis
* p < 0.001
10C-EFF-
PASI = 45 PASI = 295% improvement
Baseline Week 12
A PASI-75 Response
11C-EFF-
A PASI-50 Response
PASI = 43 PASI = 1467% improvement
Baseline Week 12
12C-EFF-
14
59
01020304050607080
Placebo Raptiva 1 mg/kg
% o
f pat
ient
s w
ith P
AS
I-50
*
n = 187 n = 369
Study 2390
Significant Effect on Rate of PASI-50 at Week 12
* Fisher’s exact test, Raptiva vs. placebo, ITT analysis
* p < 0.001
13C-EFF-
1.6
5.6
0
1
2
3
4
5
6
7Placebo Raptiva 1 mg/kg
Mea
n D
LQI I
mpr
ovem
ent
*
Study 2390
* Wilcoxon rank-sum test, Raptiva vs. placebo
Significant Effects on Dermatology Life Quality Index at Week 12
Note: Mean baseline DLQI = 12 in each treatment group
* p < 0.001
14C-EFF-
0
20
40
60
80Baseline Week 12Raptiva 1 mg/kg
Dermatology Life Quality Index Item
% o
f pat
ient
sPercent of Patients with DLQI Problems Rated ‘A Lot’ or ‘Very Much’Study 2390
15C-EFF-
Study
PASI-75 Rates at Week 12 in Placebo-Controlled Studies: Raptiva Superior to Placebo in Each Study
4 3 2 5
2724
39
22
0
10
20
30
40
50Placebo Raptiva 1 mg/kg
% o
f pat
ient
s w
ith P
AS
I-75
*
***
* Fisher’s exact test, Raptiva vs. placebo, ITT analysis
2390 (n = 556)
2059 (n = 354)
2058 (n = 332)
2600 (n = 686)
* p < 0.001
16C-EFF-
Study
PASI-75 Rates at Week 12 in Placebo-Controlled Studies: Raptiva Superior to Placebo in Each Study
4 3 2 5
2724
39
2227 28
0
10
20
30
40
50Placebo Raptiva 1 mg/kg Raptiva 2 mg/kg
% o
f pat
ient
s w
ith P
AS
I-75
*
* ** * *
2390 (n = 556)
2059 (n = 597)
2058 (n = 498)
2600 (n = 686)
* Fisher’s exact test, Raptiva vs. placebo, ITT analysis
* p < 0.001
17C-EFF-
PASI-50 Rates at Week 12Raptiva Superior to Placebo in Each Study
14 14 15 16
5952
615251
57
0
20
40
60
80Placebo Raptiva 1 mg/kg Raptiva 2 mg/kg
% o
f pat
ient
s w
ith P
AS
I-50
** ** **
2390 (n = 556)
2059 (n = 597)
2058 (n = 498)
2600 (n = 686)
* Fisher’s exact test, Raptiva vs. placebo, ITT analysis
Study
* p < 0.001
18C-EFF-
Conclusions About Raptiva Efficacy
• Significant efficacy at Week 12
• Onset of efficacy by Week 4
• Psoriasis returns when Raptiva stopped
• Significant efficacy on retreatment
• Efficacy improves with continuous treatment past 12 weeks
19C-EFF-
Study 2390
* Hierarchical t-test, Raptiva vs. placebo
Mean PASI % Improvement Over Time
Study Week
0
10
20
30
40
50
60
0 2 4 6 8 10 12
Placebo Raptiva 1 mg/kg
*
**
* *
Mea
n ±
SE %
impr
ovem
ent
from
bas
elin
e
* p < 0.001
20C-EFF-
* Hierarchical rank-sum test, Raptiva vs. placebo
Mean DLQI Improvement Over TimeStudy 2390
Study Week
0
2
4
6
8
0 4 8 12
Placebo Raptiva 1 mg/kg
*
* *
Mea
n ±
SE D
LQI i
mpr
ovem
ent
* p < 0.001
21C-EFF-
Conclusions About Raptiva Efficacy
• Significant efficacy at Week 12
• Onset of efficacy by Week 4
• Psoriasis returns when Raptiva stopped
• Significant efficacy on retreatment
• Efficacy improves with continuous treatment past 12 weeks
22C-EFF-
RandomizationDay 0
Study 2058: First 12 Weeks of Treatment, Observation, and Retreatment
Week 12 (Day 84)
ScreenPlacebo
Raptiva 1 or 2 mg/kg
ObservationPeriod
PASI 75
Placebo
Raptiva
Retreatment for 12 weeks
Relapse *
* Relapse was the loss of at least half of a patient’s PASI improvement at Week 12 of the treatment period.
23C-EFF-
Time to Relapse for Subjects with PASI-75 Response after 12 Weeks of Treatment
0.0
0.2
0.4
0.6
0.8
1.0
0 84 12 242016Weeks Since Last Dose
Pro
porti
on R
elap
sed
Study 2058, Observation Period (n = 107)
Relapse is the loss of 50% of the PASI improvement at Week 12
24C-EFF-
Raptiva is Effective upon Retreatment PASI Response Rates after 12 weeks of Retreatment in Relapsing Patients with a Previous PASI-75 Response
0
1931
67
0
20
40
60
80
100
PASI-75 Response PASI-50 Response
Placebo (n = 27) Raptiva (n = 55)
% o
f Pat
ient
s
*
** p < 0.001
* Fisher’s exact test, Raptiva vs. placebo, ITT analysis
Study 2058, Retreatment Period
25C-EFF-
Conclusions About Raptiva Efficacy
• Significant efficacy at Week 12
• Onset of efficacy by Week 4
• Psoriasis returns when Raptiva stopped
• Significant efficacy on retreatment
• Efficacy improves with continuous treatment past 12 weeks
26C-EFF-
RandomizationDay 0
Screen
Week 12(Day 84)
Placebo(n = 187)
Raptiva 1 mg/kg (n = 369)
Studies 2390 and 2391
Raptiva 1 mg/kg
Raptiva 1 mg/kg
Week 24(Day 168)
Study 2390 Study 2391
27C-EFF-
% o
f Pat
ient
s
0
20
40
60
80
100
Week 12 Week 24
≥75 50-75
59%
44%
66%
27%
Week 12 and 24 rates each based on 369 patients randomized to Raptiva on Day 0 of Study 2390
PASI Response:
Studies 2390 and 2391
Continued Treatment with Raptiva 1 mg/kg:PASI Response Rates at Weeks 12 and 24
*
*
* McNemar’s test, Week 24 vs. Week 12
* p ≤ 0.002
28C-EFF-
Efficacy of Raptiva - Summary
• Significant efficacy of Raptiva at 1 mg/kg for 12 weeks– PASI-75 response rate of 27% – PASI-50 response rate of 59% – Quality of life and patient-reported symptoms improved
• Efficacy demonstrated at 4 weeks
• Median time to relapse approximately 2 months
• Raptiva is effective on retreatment
• Improved efficacy with continuous treatment past 12 weeks– PASI-75 response rate of 44% at Week 24