1. Clinical importance and safety of ESAs for patients with Myelodysplastic Syndromes (MDS) Steven D. Gore, MD Associate Professor of Oncology Sidney Kimmel Cancer Center At Johns Hopkins Representing The MDS Foundation

2. Myelodysplastic Syndromes Heterogeneous group of clonal stem cell disorders Symptoms determined to a large extent by refractory cytopenias Refractory anemia most prominent symptom- producing cell deficit ESAs positively impact quality of life, survival, and progression to acute leukemias

3. Impact of anemia on MDS patients Chronic fatigue Decreased quality of life Medical risks of transfusion –Transfusion reactions –Iron Overload –Transmission of infection –Alloimmunization Decreased productive time due to transfusion requirements

4. 4 Amgen CONFIDENTIAL: DO NOT COPY OR DISTRIBUTE Oncology Delivery in the US is No Longer Configured to Accommodate Tranfusion In 2005, only 1 in 24 transfusions for oncology patients was given in the office setting 1 (17k vs. 417k in hospital):In 2005, only 1 in 24 transfusions for oncology patients was given in the office setting 1 (17k vs. 417k in hospital): –Extreme logistical challenges (chain of custody, staff training, transport) –Demand on staff: a typical transfusion requires 4+ hours 2 –No capacity or facilities (infusion space, staff time) Lower rates of ESA use would potentially push thousands of MDS patients back into hospitals for transfusions 1 Analysis of 2005 Physician Supplier Procedure Summary Master File 2 Uneo W, Beveridge, R & Kales AN. Presented at ASH 47th Annual Meeting, 2005 3 2006 Audit of Cytotoxic Chemotherapy Delivery, Tandem Data 4 Analysis of AHRQ Healthcare Cost and Utilization Project (HCUP) data using Clinical Classification Software (CCS) category 45 (Maintenance chemotherapy, radiotherapy)

5. ESAs for treatment of MDS- associated anemia ESAs effective and safe in MDS Studied in hundreds of patients over greater than 10 years No evidence of increased incidence of thrombosis in this population

6. Randomized Trial of EPO versus observation (ECOG) 105 MDS patients Supportive care versus EPO 150 u/kg/day; increase to 300 u/kg/day if no response Erythroid response rate 35% in EPO arm versus 9% in supportive care Response rate 30% in supportive care patients crossed over after worsening transfusion requirement Development of AML –3.6% of patients in supportive care –0% in EPO arm Miller, KB et al. Blood 104:24a, 2004

7. EPO: Scandinavian Experience 129 MDS patients followed for at least 45 months EPO plus/minus G-CSF Hgb of 11.5 g/dL achieved in 39% Transfusion independence in 29% of transfusion dependent patients Median duration of response 23 months No difference in survival compared to matched historical controls Jadersten et al. Blood 2005. 106: 803-11

8. ESAs may improve survival in some MDS patients Comparison of Nordic patients treated with EPO plus G-CSF to supportive care only patients from Pavia, IT 176 transfusion-dependent; 187 untransfused but Hgb < 10 g/dL In patients with low transfusion need (< 2U RBC/month), survival superior in treated group (HR 0.57, p = 0.015) Jadersten et al. Blood 2006. 108:158a

9. Further evidence of survival benefit Retrospective comparison of 284 patients from France treated with EPO +/- G-CSF to 163 supportive care patients (IPSS data base) Multivariate analysis: –EPO treated patients less likely to develop AML (HR 0.2 [0.1 – 0.3]) –Better survival (HR 0.26 [0.18 – 0.38]) Park et al. International MDS Symposium, 2007

10. Appropriate MDS patients can be selected for ESA therapy Serum epo concentrations < 500 u/mL Low transfusion requirement Addition of G-CSF patients for subset Monitor response with monthly reticulocyte counts May require high doses (1000 – 2000 u/kg/week epo; 300 mcg/week darbo)

11. Summary Chronic transfusions represent a major burden to quality of life for MDS patients ESAs provide important palliation of anemia in a significant subset of MDS patients ESAs may improve survival in a subset of MDS patients Extremely well-tolerated in this patient population Extremely important to maintain access to ESAs for selected MDS patients