Before, Frank's immune cells could

Transcription

1 Before, Frank's immune cells could barely recognize a prostate cancer cell. Now, they are focused on it.

2 Stimulate an immune response against advanced prostate cancer Extend median survival beyond 2 years in men with asymptomatic or minimally symptomatic metastatic CRPC. PROVENGE is the first in a new class of therapy that is designed to activate a patient s own antigen-presenting cells (APCs) to stimulate an immune response against prostate cancer. INDICATION: PROVENGE (sipuleucel-t) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. IMPORTANT SAFETY INFORMATION: PROVENGE is intended solely for autologous use and is not routinely tested for transmissible infectious diseases. In controlled clinical trials, serious adverse events reported in the PROVENGE group include acute infusion reactions (occurring within 1 day of infusion) and cerebrovascular events. Severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group. The precise mechanism of action of PROVENGE is not known. The most common adverse events (incidence 15%) reported in the PROVENGE group are chills, fatigue, fever, back pain, nausea, joint ache, and headache. Please see Important Safety Information on page 6.

3 Making the decision to treat PROVENGE expands your therapeutic options Prostate cancer is the second leading cause of cancer-related death in men 1 In advanced prostate cancer, the disease will eventually progress in most men on androgen deprivation therapy 2 Metastatic CRPC is an aggressive disease with median survival from 15.5 months to * Vigilant monitoring and the resulting early diagnosis of metastatic disease provide an opportunity to treat these patients before they are symptomatic. Early identification of progression allows you to treat patients who have: Metastatic CRPC that is asymptomatic or minimally symptomatic, defined as: No moderate-to-severe prostate cancer related pain No use of narcotics for cancer-related pain Now with PROVENGE, you have another way to take action for your asymptomatic or minimally symptomatic metastatic CRPC patients. *Median survival range is based on the control group of recent clinical studies in this patient population. 1. American Cancer Society. Cancer Facts & Figures Atlanta, GA: American Cancer Society; Kantoff PW, Carroll PR, D Amico AV, eds. Prostate Cancer: Principles and Practice. Philadelphia, PA: Lippincott Williams & Wilkins; Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363: Stimulate a Response Please see enclosed full Prescribing Information for PROVENGE. 2

4 Training the immune cells PROVENGE the first FDA-approved autologous cellular immunotherapy The active component of PROVENGE consists of a patient s own APCs that have been cultured with a recombinant antigen to stimulate the body s immune system against prostate cancer PROVENGE Proposed Mechanism of Action PROSTATIC ACID PHOSPHATASE (PAP) AN ANTIGEN 1 EXPRESSED IN MORE THAN 95% OF PROSTATE CANCERS 1 GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) AN IMMUNE-CELL ACTIVATOR PAP-GM-CSF ANTIGEN COMBINES WITH RESTING APC APC TAKES UP THE PAP-GM-CSF PAP-GM-CSF IS PROCESSED AND PRESENTED ON THE SURFACE OF THE APC ACTIVE T CELL INACTIVE T CELL INFUSE PATIENT T CELLS PROLIFERATE TO TARGET PROSTATE CANCER CELLS PROVENGE ACTIVATES T CELLS IN THE BODY PAP-GM-CSF LOADED APCs ARE NOW THE ACTIVE COMPONENT OF PROVENGE The precise mechanism of action of PROVENGE is not known. The precise mechanism of action of PROVENGE is not known. 1. Goldstein NS. Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. Am J Clin Pathol. 2002;117: Please see Important Safety Information on page 6.

5 Primary endpoint: overall survival The PROVENGE pivotal trial The pivotal trial was a randomized, double-blind, multicenter, controlled* Phase 3 trial of 512 patients with asymptomatic or minimally symptomatic metastatic CRPC Primary endpoint Overall survival Secondary endpoint Time to objective disease progression Trial Design 1 Asymptomatic or Minimally Symptomatic Metastatic CRPC (N=512) 2:1 PROVENGE Q2 weeks x 3 Control* Q2 weeks x 3 PROGRESSION Treated at Physician Discretion Treated at Physician Discretion Including Entry Into Phase 2, Open-Label Protocol SURVIVAL *Control was nonactivated, autologous, peripheral blood mononuclear cells. After independent confirmation of objective disease progression: All patients were treated at their physicians discretion Patients in the control group had the option to enter a Phase 2, open-label protocol Treatment An autologous immunotherapy made from cells that were cryopreserved at the time of control generation Participation 63.7% of patients in the control group entered the Phase 2 protocol 1. Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363: Stimulate a Response Please see enclosed full Prescribing Information for PROVENGE. 4

6 Reporting results PROVENGE extends median survival beyond 2 years Reduction in risk of death: 22.5% for patients in the PROVENGE group compared with patients in the control* group (HR=0.775 [95% CI: 0.614, 0.979] P=.032) Overall Survival 1,2 100 PROVENGE (n=341) Control (n=171) 75 Reduction in risk of death: 22.5% Survival (%) months 25.8 months HR=0.775 (95% CI: 0.614, 0.979) P= Time From Randomization (Months) Data originally published in the New England Journal of Medicine: Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363: An earlier Phase 3 trial (D9901) supports survival results: 25.9 months for patients in the PROVENGE group compared with 21.4 months for patients in the control group (HR=0.586 [95% CI: 0.388, 0.884] P=.010) Analyses of time to disease progression did not meet statistical significance in any Phase 3 study of PROVENGE *Control was nonactivated, autologous, peripheral blood mononuclear cells. In Study D9901, all patients were followed for survival; however, overall survival was not a prespecified endpoint. 1. PROVENGE [package insert]. Dendreon Corporation; April The Kantoff precise PW, Higano mechanism CS, Shore ND, of action et al; for of the PROVENGE IMPACT Study Investigators. is not known. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363: Please see Important Safety Information on page 6.

7 Extending survival PROVENGE helps your patients continue their fight against advanced prostate cancer Survival probabilities: 1, 2, 3, and 4 years 1 Kaplan-Meier Survival Rate Estimates in the Pivotal Trial 1 Percentage of Patients Alive: ITT Population (95% CI) 1 year 2 years 3 years 4 years PROVENGE 81.1 (76.9, 85.3) n= (46.4, 57.7) n= (25.7, 37.8) n= (14.0, 26.9) n=14 Control 72.4 (65.6, 79.1) n= (33.5, 49.9) n= (15.5, 30.5) n= (8.5, 23.4) n= Percentage Increase in PROVENGE Group vs Control Group* year 2 years 3 years 4 years *(Percent PROVENGE percent control)/percent control. INDICATION: PROVENGE (sipuleucel-t) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. IMPORTANT SAFETY INFORMATION: PROVENGE is intended solely for autologous use and is not routinely tested for transmissible infectious diseases. In controlled clinical trials, serious adverse events reported in the PROVENGE group include acute infusion reactions (occurring within 1 day of infusion) and cerebrovascular events. Severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group. The most common adverse events (incidence 15%) reported in the PROVENGE group are chills, fatigue, fever, back pain, nausea, joint ache, and headache. 1. Data on file. Dendreon Corporation. Stimulate a Response Please see enclosed full Prescribing Information for PROVENGE. 6

8 Analyzing safety With PROVENGE, the most common adverse events are primarily mild or moderate For 67.4% of patients reporting adverse events in the PROVENGE group, these events were mild or moderate. Most Common Adverse Events 1 * ADVERSE EVENT Chills Fatigue PROVENGE (n=601) (%) ANY GRADE Control (n=303) (%) The most common adverse events ( 15%) reported in the PROVENGE group are chills, fatigue, fever, back pain, nausea, joint ache, and headache. Fever Back pain Nausea Joint ache Headache * All grades reported in 15% of patients randomized to PROVENGE. The safety analysis is based on 601 prostate cancer patients in the PROVENGE group who underwent at least 1 leukapheresis procedure in Phase 3 clinical trials. Control was nonactivated, autologous, peripheral blood mononuclear cells. Acute infusion reactions: Acute infusion reactions (occurring within 1 day of infusion) were reported in 71.2% of patients in the PROVENGE group In 95.1% of patients, acute infusion reactions were mild or moderate The most common acute infusion reactions ( 20%) were chills, fever, and fatigue Fevers (71.9%) and chills (89.0%) generally resolved within 2 days 1.2% of patients in the PROVENGE group were hospitalized within 1 day of infusion for management of acute infusion reactions No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group The precise mechanism of action of PROVENGE is not known. 1. PROVENGE [package insert]. Dendreon Corporation; April Please see Important Safety Information on page 6.

9 Considering the data A demonstrated safety profile In the PROVENGE group: Grade 3 adverse events were reported in 23.6% of patients compared with 25.1% of patients in the control group Grade 4 adverse events were reported in 4.0% of patients compared with 3.3% of patients in the control group Grade 5 adverse events were reported in 3.3% of patients compared with 3.6% of patients in the control group Serious adverse events included acute infusion reactions and cerebrovascular events Cerebrovascular events, including hemorrhagic and ischemic strokes, were reported in 3.5% of patients compared with 2.6% of patients in the control group Grades 3 5 Adverse Events 1,2 * ADVERSE EVENT Any adverse event Back pain Chills Anemia Joint ache Cerebrovascular accident Dyspnea Spinal cord compression Pain Asthenia Fatigue Hematuria Fever PROVENGE (n=601) (%) GRADES 3 5 Control (n=303) (%) *Reported in 1% of patients in the PROVENGE group. Control was nonactivated, autologous, peripheral blood mononuclear cells. Only 1.5% of patients in the pivotal trial discontinued treatment with PROVENGE due to adverse events. 1. PROVENGE [package insert]. Dendreon Corporation; April Data on file. Dendreon Corporation. Stimulate a Response Please see enclosed full Prescribing Information for PROVENGE. 8

10 Knowing who to treat Recognizing the PROVENGE patient PROVENGE is indicated for men with: Metastatic CRPC Asymptomatic or minimally symptomatic disease, defined as: No moderate-to-severe prostate cancer related pain No use of narcotics for cancer-related pain Certain additional criteria from the PROVENGE pivotal trial for consideration: No visceral (lung, liver, or brain) metastases ECOG Performance Status 0 or 1 No treatment with chemotherapy in at least the previous 3 months No treatment within 28 days with systemic corticosteroids The precise mechanism of action of PROVENGE is not known. 9 Please see Important Safety Information on page 6.

11 Expanding options for your patients Creating a new opportunity in your treatment of advanced prostate cancer NCCN Guidelines: PROVENGE Included for Treatment of Advanced Prostate Cancer 1 ADT Progression M1 * Asymptomatic or minimally symptomatic with ECOG 0-1 Asymptomatic Symptomatic Visceral disease PROVENGE (sipuleucel-t) Secondary hormone therapy Clinical trial Docetaxel Mitoxantrone Palliative radiotherapy or radionuclide for symptomatic bone metastases Clinical trial ADT=androgen deprivation therapy. *M1=Distant metastasis. Maintain castrate serum levels of testosterone and use denosumab or zoledronic acid if there are bone metastases. Cabazitaxel Salvage chemotherapy Docetaxel rechallenge Mitoxantrone Secondary hormone therapy Clinical trial Adapted from NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. V Men with less advanced disease (no or minimal symptoms) should consider immunotherapy with PROVENGE; men who are symptomatic should be considered for chemotherapy. NCCN Guidelines 1 PROVENGE did not preclude use of subsequent therapies. In the pivotal trial, 81.8% of patients in the PROVENGE group received additional anticancer treatments 2 1. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. V National Comprehensive Cancer Network Web site. Accessed December 14, Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration resistant prostate cancer. N Engl J Med. 2010;363: Stimulate a Response Please see enclosed full Prescribing Information for PROVENGE. 10

12 Leukapheresis Procedure Facilitating treatment PROVENGE transforming therapy with Leukapheresis Procedure a regimen that is complete in 3 cycles Treatment can be completed in approximately 1 month 1 Median time was 28 days in the pivotal trial 1 PROVENGE is administered as 3 infusions, generally 2 weeks apart.* Each infusion is preceded by a standard leukapheresis procedure A Sample PROVENGE Schedule Leukapheresis Procedure Leukapheresis Procedure Leukapheresis Procedure Each infusion takes approximately 60 minutes. To help minimize infusion reactions such as chills and fever, approximately 30 minutes prior to infusion with PROVENGE, pretreat patients orally with acetaminophen and an antihistamine such as diphenhydramine 91.8% of patients in the PROVENGE group in the pivotal trial received a complete course of therapy. 2 PROVENGE is designed to stimulate the immune system: Concurrent use of chemotherapy or immunosuppressive agents (such as systemic corticosteroids) may alter efficacy and/or safety Carefully evaluate patients to determine whether it is medically appropriate to reduce or discontinue immunosuppressive agents prior to beginning treatment cycles *The dosing interval ranged from 1 to 15 weeks in controlled clinical trials. 1. Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration The resistant precise prostate mechanism cancer. N Engl of J action Med. 2010;363: of PROVENGE is not known. 2. Data on file. Dendreon Corporation. 11 Please see Important Safety Information on page 6.

13 Handling the details One call activates Dendreon ON Call for support services throughout therapy Patient Assistance Programs Dedicated case managers to provide referrals to or information on: Independent foundations that may assist patients with co-pays, co-insurance, and deductible costs* Independent foundations that may assist patients with treatment-related travel costs* Reimbursement Support Dedicated case managers to help: Verify benefits Assist with prior authorizations Support claims appeals Provide referrals to local field personnel who can offer assistance with reimbursement related questions Product Support Dedicated case managers who: Generate patient schedules and leukapheresis reminder calls Ensure timely product ordering and delivery Handle product spoilage and returns Facilitate extended payment terms Please ask your Dendreon sales representative how to become an infusion site for PROVENGE therapy. Or, ask how you can refer patients to a site that has already been approved. *Co-pay and travel assistance foundations provide assistance regardless of the choice of medicine, and decisions are based on financial need and according to criteria established by individual foundations. Dendreon can assist patients by referring them to these independent organizations. Dendreon cannot guarantee that patients will be eligible for or receive assistance after referral. Dendreon does not have controlling or managerial influence on these independent organizations. Services vary by office based on application criteria and are subject to change or discontinuation. Stimulate a Response Please see enclosed full Prescribing Information for PROVENGE. 12

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16 Stimulate an immune response against prostate cancer PROVENGE the first in a new class of therapy... Extends median survival beyond 2 years 25.8 months compared with 21.7 months for patients in the control group (P=.032) Therapy completed in 3 cycles 3 infusions, at approximately 2-week intervals* Most common adverse events are primarily mild or moderate chills, fatigue, fever, back pain, nausea, joint ache, and headache Survival (%) Overall Survival 1, months PROVENGE (n=341) Control (n=171) 25.8 months Time From Randomization (Months) Reduction in risk of death: 22.5% HR=0.775 (95% CI: 0.614, 0.979) P= Data originally published in the New England Journal of Medicine: Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363: INDICATION: PROVENGE (sipuleucel-t) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. IMPORTANT SAFETY INFORMATION: PROVENGE is intended solely for autologous use and is not routinely tested for transmissible infectious diseases. In controlled clinical trials, serious adverse events reported in the PROVENGE group include acute infusion reactions (occurring within 1 day of infusion) and cerebrovascular events. Severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group. The most common adverse events (incidence 15%) reported in the PROVENGE group are chills, fatigue, fever, back pain, nausea, joint ache, and headache. Please see enclosed full Prescribing Information for PROVENGE. * The dosing interval ranged from 1 to 15 weeks in controlled clinical trials. 1. PROVENGE [package insert]. Dendreon Corporation; April Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363: Dendreon Corporation. All rights reserved. January Printed in the U.S.A. Dendreon, the Dendreon logo, and PROVENGE are registered trademarks of Dendreon Corporation. P-A Stimulate a Response