SEATTLE and DENVER, April 19 /PRNewswire-FirstCall/ -- Researchers from Dendreon Corporation presented today data from its PROTECT (PROvenge Treatment and Early Cancer Treatment) or P-11 Phase 3 study suggesting that PROVENGE(R) (sipuleucel-T) induces long-term memory immune responses that are durable and can be maintained following boosting. The results of the study also indicate that CD54 upregulation on Antigen Presenting Cells (APCs), a measure of potency, is a correlate of immune activation.
P-11 is an ongoing Phase 3 clinical trial designed to evaluate the safety and biologic activity of PROVENGE in patients with non-metastatic androgen-dependent (hormone sensitive) prostate cancer who have had a prostate-specific antigen (PSA) recurrence following surgical removal of the prostate. Patients were randomized to PROVENGE or placebo following 3 months of hormone therapy. This study evaluated CD54 upregulation and peripheral immune responses in men enrolled in the trial.
PROVENGE or placebo was administered at weeks zero, two and four. A treatment booster infusion of PROVENGE or placebo was offered after confirmed PSA greater than or equal to 3.0ng/mL. Immune responses were measured pre-treatment, at weeks four and 13, and at four and 13 weeks following the booster infusion.
At the week zero dose of PROVENGE, the expression of CD54 on APCs was upregulated 5.8 fold. At the week two dose, it was 10.1 fold, significantly increased from week 0 (p < 0.001). The increase in CD54 upregulation persisted at week four (10.7 fold) and at the time of the booster infusion (12.0 fold). There was an increase in cellular immune response between pre-treatment and week four (p < 0.001), which persisted through 13 weeks after the booster infusion (p < 0.001). The PROVENGE booster infusions occurred from 0.2 to 5.5 years (median 1.1 years) after the week four dose.
Data is being presented in a session titled, "Cancer Vaccines: Human Studies" in a presentation titled, "Antigen presenting cell activation in sipuleucel-T and long-term immune responses in prostate cancer trial" today at 8:00 AM MDT at the 100th Annual Meeting of the Association for Cancer Research in Denver, Colorado.
"We are encouraged to see that CD54 upregulation in APCs is maintained after boosting in men with androgen-dependent prostate cancer," said David Urdal, chief scientific officer of Dendreon. "This pattern of CD54 upregulation suggests that the first dose 'primes' the immune system for subsequent 'memory' responses and is consistent with that observed in our studies of men with androgen-independent disease where the cumulative CD54 upregulation dose correlated with survival. We also are encouraged by these data which suggest that the immune response generated by PROVENGE is durable for a year or more after initial treatment and that it can be maintained following boosting."
Study Design
The study, known as PROTECT (PROvenge Treatment and Early Cancer Treatment) or P-11, is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety and biologic activity of PROVENGE in men with non-metastatic androgen-dependent prostate cancer who have had a prostate-specific antigen (PSA) recurrence following surgical removal of the prostate. A total of 176 patients at 19 sites in the United States were randomized two to one to receive PROVENGE or placebo following a three-month course of hormonal therapy. Patients were then followed with serial PSA measurements to evaluate the impact of PROVENGE on PSA and PSADT (PSA doubling time). At the time of biochemical progression, defined as a PSA of 3 ng/mL or greater, men became eligible for one booster infusion of either PROVENGE or placebo in accordance with the treatment arm to which they were randomized. Patients continue to be followed for the clinical endpoints of time to distant failure, which typically would be the appearance of a positive bone scan, and for overall survival.
About PROVENGE
PROVENGE (R) (sipuleucel-T), an investigational product in development for men with androgen-independent prostate cancer, may represent the first product in a new class of active cellular immunotherapies (ACIs). PROVENGE and other ACIs are uniquely designed to use live human cells to engage the patient's own immune system with the goal of eliciting a specific long-lasting response against cancer. In controlled clinical trials, the most common adverse events were chills, fever, headache, fatigue, shortness of breath, vomiting and tremor. These events were primarily low grade with a short duration of 1-2 days following infusion.
About Prostate Cancer
Prostate cancer is the most common non-skin cancer in the United States and the third most common cancer worldwide. More than one million men in the United States have prostate cancer, with an estimated 186,320 new cases and approximately 28,660 men who were expected to die from the disease in 2008. Currently there are limited treatment options for men with advanced, metastatic prostate cancer.
About Dendreon
Dendreon Corporation is a biotechnology company whose mission is to target cancer and transform lives through the discovery, development and commercialization of novel therapeutics. The Company applies its expertise in antigen identification, engineering and cell processing to produce active cellular immunotherapy product candidates designed to stimulate an immune response. Dendreon is also developing an orally-available small molecule that targets TRPM8 that could be applicable to multiple types of cancer as well as benign prostatic hyperplasia. The Company has its headquarters in Seattle, Washington and is traded on the Nasdaq Global Market under the symbol DNDN. For more information about the Company and its programs, visit http://www.dendreon.com/.
Except for historical information contained herein, this news release contains forward-looking statements that are subject to risks and uncertainties surrounding the efficacy of PROVENGE to treat men suffering from prostate cancer, risks and uncertainties surrounding the presentation of data to the FDA and approval of product applications by the FDA and risks and uncertainties inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics. Factors that may cause such differences include risks related to our limited operating history, risks associated with completing our clinical trials, the risk that the safety and/or efficacy results of existing clinical trials or from additional clinical trials for PROVENGE will not support approval for a biologics license, the risk that the FDA may interpret data differently than we do or require more data or a more rigorous analysis of data than expected, the risk that the FDA will not approve a product for which a biologics license has been applied, the risk that the results of a clinical trial for PROVENGE or other product may not be indicative of results obtained in a later clinical trial, risks that we may lack the financial resources and access to capital to fund required clinical trials or commercialization of PROVENGE, our dependence on the efforts of third parties, and our dependence on intellectual property. Further information on the factors and risks that could affect Dendreon's business, financial condition and results of operations are contained in Dendreon's public disclosure filings with the U.S. Securities and Exchange Commission, which are available at http://www.sec.gov/.
Dendreon Corporation
CONTACT: Investors: Jennifer Cook Williams, Dendreon Corporation,
+1-206-829-1500; Media: Katherine Stueland, WeissComm Partners,
+1-312-208-0320
Web Site: http://www.dendreon.com/
