Raptiva TM (efalizumab) Efficacy

1. RaptivaTM (efalizumab) Efficacy Lee Kaiser, PhD DirectorClinical Biostatistics Genentech, Inc.

2. Phase III Studies

3. 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

4. Study 2390:Pivotal Phase III Efficacy Study Entrance criteria • Plaque psoriasis ≥ 6 months • BSA ≥ 10% • PASI ≥ 12 • Candidate for, or history of, systemic therapy Placebo (n = 187) Screen Raptiva 1 mg/kg (n = 369) Randomization Day 0 Primary Analysis Week 12 (Day 84)

5. 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%

6. 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

7. Study 2390: Demographics

8. Study 2390: Baseline Characteristics

9. n = 187 n = 369 Significant Effect on the Primary Endpoint:Rate of PASI-75 at Week 12 Study 2390 * * p < 0.001 % of patients with PASI-75 * Fisher’s exact test, Raptiva vs. placebo, ITT analysis

10. A PASI-75 Response Baseline Week 12 PASI = 45 PASI = 2 95% improvement

11. A PASI-50 Response Baseline Week 12 PASI = 14 67% improvement PASI = 43

12. n = 187 n = 369 Significant Effect on Rate of PASI-50 at Week 12 Study 2390 * * p < 0.001 % of patients with PASI-50 * Fisher’s exact test, Raptiva vs. placebo, ITT analysis

13. Significant Effects on Dermatology Life Quality Index at Week 12 Study 2390 * * p < 0.001 Mean DLQI Improvement Note: Mean baseline DLQI = 12 in each treatment group * Wilcoxon rank-sum test, Raptiva vs. placebo

14. Percent of Patients with DLQI Problems Rated ‘A Lot’ or ‘Very Much’ Study 2390 Raptiva 1 mg/kg % of patients Dermatology Life Quality Index Item

15. PASI-75 Rates at Week 12 in Placebo-Controlled Studies: Raptiva Superior to Placebo in Each Study * p < 0.001 * * * * % of patients with PASI-75 2600 (n = 686) 2058 (n = 332) 2059 (n = 354) 2390 (n = 556) Study * Fisher’s exact test, Raptiva vs. placebo, ITT analysis

16. PASI-75 Rates at Week 12 in Placebo-Controlled Studies: Raptiva Superior to Placebo in Each Study * p < 0.001 * * * * * * % of patients with PASI-75 2390 (n = 556) 2600 (n = 686) 2058 (n = 498) 2059 (n = 597) Study * Fisher’s exact test, Raptiva vs. placebo, ITT analysis

17. PASI-50 Rates at Week 12Raptiva Superior to Placebo in Each Study * p < 0.001 * * * * * * % of patients with PASI-50 2390 (n = 556) 2600 (n = 686) 2058 (n = 498) 2059 (n = 597) Study * Fisher’s exact test, Raptiva vs. placebo, ITT analysis

18. 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

19. * * p < 0.001 * * * Mean ± SE % improvement from baseline * Study Week Mean PASI % Improvement Over Time Study 2390 * Hierarchical t-test, Raptiva vs. placebo

20. * p < 0.001 * * * Mean ± SE DLQI improvement Study Week Mean DLQI Improvement Over Time Study 2390 * Hierarchical rank-sum test, Raptiva vs. placebo

21. Conclusions About Raptiva Efficacy • Significant efficacy at Week 12 • Onset of efficacy by Week 4 • Psoriasis returns when Raptivastopped • Significant efficacy on retreatment • Efficacy improves with continuous treatment past 12 weeks

22. Study 2058: First 12 Weeks of Treatment, Observation, and Retreatment Placebo Raptiva Placebo Relapse * Retreatment for 12 weeks Screen Raptiva 1 or 2 mg/kg ObservationPeriod PASI 75 Randomization Day 0 Week 12 (Day 84) * Relapse was the loss of at least half of a patient’s PASI improvement at Week 12 of the treatment period.

23. 0 4 8 12 16 20 24 Time to Relapse for Subjects with PASI-75 Response after 12 Weeks of Treatment Study 2058, Observation Period (n = 107) Proportion Relapsed Weeks Since Last Dose Relapse is the loss of 50% of the PASI improvement at Week 12

24. Raptiva is Effective upon Retreatment PASI Response Rates after 12 weeks of Retreatment in Relapsing Patients with a Previous PASI-75 Response Study 2058, Retreatment Period * p < 0.001 * % of Patients * * Fisher’s exact test, Raptiva vs. placebo, ITT analysis

25. 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

26. Studies 2390 and 2391 Study 2390 Study 2391 Placebo(n = 187) Raptiva 1 mg/kg Screen Raptiva 1 mg/kg (n = 369) Raptiva 1 mg/kg Randomization Day 0 Week 24(Day 168) Week 12(Day 84)

27. Continued Treatment with Raptiva 1 mg/kg:PASI Response Rates at Weeks 12 and 24 Studies 2390 and 2391 PASI Response: * p ≤ 0.002 * 66% 59% % of Patients * 44% 27% Week 12 and 24 rates each based on 369 patients randomized to Raptiva on Day 0 of Study 2390 * McNemar’s test, Week 24 vs. Week 12

28. 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