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Raptiva™ (efalizumab) Benefit:Risk Assessment

Charles Johnson, MB, ChB

Senior DirectorHead of Specialty Biotherapeutics

Genentech, Inc.

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A Significant Unmet Medical Need Exists

• Psoriasis is a chronic life-long disease with QOL impact similar to other major diseases(arthritis, diabetes, cancer, cardiovascular disease)

• Common physical symptoms of chronic psoriasis include skin pain, itching, and bleeding; these physical symptoms impair quality of life

• Topical medications are insufficient to treat moderate to severe disease

• Currently approved therapies for moderate to severe disease are effective, but have significant safety limitations and accessibility issues

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Characteristics of Raptiva in Psoriasis

• Dosed once weekly as a single SC injection

• Has an early onset of action

• Effective at 12 weeks

– 27% of patients achieve PASI-75 (12 weeks)

– 59% of patients achieve PASI-50 (12 weeks)

• Extended treatment improves response at 24 weeks

– 44% of patients achieve PASI-75 (24 weeks)

– 66% of patients achieve PASI-50 (24 weeks)

• Response maintained with one year continuous therapy

– 45% of patients achieve PASI-75

• Therefore best used as continuous therapy

• Safe and well tolerated

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Raptiva Improves Plaque Psoriasis

Day 0PASI 50.4

Day 91PASI 2.1PGA Excellent

Before Treatment After Treatment

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Quality of Life Improves Quickly

* Hierarchical rank-sum test, Raptiva vs. placebo

Study 2390

Study Week

0

2

4

6

8

0 4 8 12

Placebo Raptiva 1 mg/kg

*

* *

Me

an

± S

E D

LQ

I im

pro

ve

me

nt

* p < 0.001

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Key Safety Outcomes

• Extensive safety database: 2762 treated patients

• Most common adverse events are mild flu-like symptoms following first 2 Raptiva injections

• Favorable overall adverse event profile, including infection and malignancy

• Psoriasis adverse events are infrequent and manageable

• Infrequent cases of reversible thrombocytopenia

• No evidence of renal or hepatic dysfunction

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Raptiva is Safe and Effective

• Meaningful clinical benefit has been demonstrated in patients with moderate-to-severe plaque psoriasis

• Ongoing therapy with Raptiva provides extended benefit, with no increase in adverse events as exposure is prolonged

• Frequency of psoriasis adverse events is mitigated by:

– Continued therapy in responders

– Limiting dose to 1 mg/kg

– Transition in non-responders (12 weeks)

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Benefit:Risk Conclusions

• Based on the robust efficacy and reasonable safety, Raptiva should be available as a therapeutic option for patients with moderate to severe plaque psoriasis

• Post approval surveillance will further clarify the long term safety of Raptiva

Raptiva™ Proposed Indication

Raptiva™ is indicated for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis.