# Presentation: 763041

## Agenda

**Overview**
**Burt Adelman MD**
**Efficacy and Pharmacodynamics**
**Akshay Vaishnaw MD, PhD**
**Safety**
**Gloria Vigliani MD**
**Alefacept Risk Benefit Profile**
**Mark Lebwohl MD**

## Psoriasis

**Psoriasis**

## Psoriasis

## Psoriasis

## Psoriasis

## Psoriasis

## Alefacept Clinical Trial Patients – Baseline

**Alefacept Clinical Trial Patients – Baseline**

## Impact of Psoriasis

**Psoriasis causes as much disability as other major medical diseases (Rapp, Feldman, et. al., *****Journal ******of the American Academy of Dermatology*****)**

## Light Therapy Unit

**Light Therapy Unit**

## Limitations of PUVA

**Non-melanoma skin cancer occurring in patients treated with PUVA five to ten years after first treatment (Stern et al., *****J Invest Dermatol***** , 1988)**
**Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study (Stern et al. *****N Engl J Med***** 1997)**

## Limitations of Methotrexate

**Complications in methotrexate treatment of psoriasis with particular reference to liver fibrosis (Ashton et al.,***** Invest Dermatol*****, 1982)**
**Methotrexate in psoriasis: consensus conference (Roenigk HH Jr, Auerbach R, Maibach H, Weinstein G, Lebwohl M, (*****J Am Acad Dermatol, *****1998)**
**A 21-year experience with major hemorrhage after percutaneous liver biopsy (McGill et al., *****Gastroenterology, *****1990)**
**Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology (Kremer et al., *****Arthritis Rheum *****1994)**

## Limitations of Methotrexate

## Methotrexate

**Pancytopenia associated with low dose methotrexate therapy.  A regional survey.  (al-Awadhi, et al., *****Journal of Rheumatology*****, 1993)**
**15 cases from Ottawa physician survey and 2 teaching hospitals**
**2 deaths, 1 attributed to methotrexate**

## Retinoid Side Effects

**Retinoid Side Effects**

## Retinoid Side Effects

## Limitations of Cyclosporine A

**Renal biopsy findings in long-term cyclosporin treatment of psoriasis  (Zachariae et al., *****Br J Dermatol 1997*****)**
**30 psoriatics, 6months - 8 years, 2.5 - 6 mg/kg/d**
**after 2 years, all showed features of CsA nephropathy**
**arteriolar hyalinosis, focal interstitial fibrosis, sclerotic glomeruli**

## What Does Alefacept Offer? 

**Baseline**
**PASI 14.2**

**2 Weeks After Last Dose**
**PASI 9.5**
***33% PASI Reduction***

**12 Weeks After Last Dose**
**PASI 4.8**
***66% PASI Reduction***

**What Does Alefacept Offer? **

## PASI 50

- 131-201

**PASI 50**

**Baseline**
**PASI 21.3**

**2 Weeks After Last Dose**
**PASI 5.8**
***73% PASI Reduction***

**12 Weeks After Last Dose**
**PASI 6.5**
***69% PASI Reduction***

## PASI 50

- 151-206

**Baseline**
**PASI 28.7**

**2 Weeks After Last Dose**
**PASI 9.6**
***67% PASI Reduction***

**12 Weeks After Last Dose**
**PASI 11.4**
***60% PASI Reduction***

## PASI 50

- 153-205

**Baseline**
**PASI 18.7**

**2 Weeks After Last Dose**
**PASI 5.7**
***70% PASI Reduction***

**12 Weeks After Last Dose**
**PASI 9.6**
***49% PASI Reduction***

**PASI 50**

## PASI 75 After Primary Endpoint

**Baseline**
**PASI 17.8**

**2 Weeks After Last Dose**
**PASI 9.8**
***45% PASI Reduction***

**12 Weeks After Last Dose**
**PASI 3.9**
***78% PASI Reduction***

**PASI 75 After Primary Endpoint**

## PASI 75

**Baseline**
**PASI 30**

**2 Weeks After Last Dose**
**PASI 6.1**
***80% PASI Reduction***

**12 Weeks After Last Dose**
**PASI 3.5**
***88% PASI Reduction***

**PASI 75**

## Duration

- 154-202

**Baseline**
**PASI 22.2**

**2 Weeks After Last Dose**
**PASI 2**
***91% PASI Reduction***

**12 Weeks After Last Dose**
**PASI 0**
***100% PASI Reduction***

**Duration**

## Duration

**23 Weeks After Last Dose**
**PASI 3.6**
***84% PASI Reduction***

**37 Weeks After Last Dose**
**PASI 8.7**
***61% PASI Reduction***

**Duration**

## Who Should Receive Alefacept?

**Patients with challenging disease**
**Not candidate for topical monotherapy**
**UVB is impractical**
**Candidate for PUVA, Methotrexate, or Cyclosporine**

## Managing the Alefacept – Treated Patient

**Select dosing route – IM and IV**
**IV offers single needlestick**
**Patient 90% BSA can’t get IM**
**Routine monitoring (lymphocyte counts) and evaluation during therapy**
**Future courses administered to previous responders**
**Continued observation of patients for as yet undetected long term issues**

## Overall Benefit / Risk Ratio

**Long term exposure will be limited to those patients that respond to therapy **
**Majority of patients benefit from therapy**
**Lymphocyte counts are monitorable**
**Duration superior to current therapy**
**No hepatotoxicity, no nephrotoxicity**

## Alefacept Conclusions

**Selective and novel approach targeting memory T cells**
**T-cell effects correlate with efficacy but not with adverse safety outcomes **
**Clinically meaningful benefit in the majority of patients**
**Significant duration of remission**
**Improvements in disease activity associated with QOL benefit**
**Well-tolerated**
**First systemic disease-remittive agent **