January 31, 2012 – Dendreon Corporation (NASDAQ: DNDN) today announced the following PROVENGE ® data will be presented at the American Society of Clinical Oncology 2012 Genitourinary Cancers Symposium (ASCO-GU), taking place February 2-4, 2012 in San Francisco, California.
- “An Analysis to Quantify the Overall Survival (OS) Benefit of Sipuleucel-T Accounting for the Crossover in the Control Arm of the IMPACT Study,” abstract #144. General Poster Session B: Prostate Cancer (D7) from 5:05 to 6:35 p.m. PT on Thursday, February 2, 2012.
- “Sipuleucel-T Product Characterization Across Different Disease States of Prostate Cancer,” abstract #42. General Poster Session A: Prostate Cancer (C8) from 11:45 a.m. to 1:15 p.m. PT on Thursday, February 2, 2012.
- “Neoadjuvant Sipuleucel-T in Patients with Localized Prostate Cancer: Immune Responses in Prostate Tumor Tissue,” abstract #181. General Poster Session C: Prostate Cancer (B1) from 12:15 to 1:45 p.m. PT on Friday, February 3, 2012.
- “Evaluation of Immune Activation Following Neoadjuvant Sipuleucel-T in Subjects with Localized Prostate Cancer,” abstract #178. General Poster Session C: Prostate Cancer (A7) from 12:15 to 1:45 p.m. PT on Friday, February 3, 2012.
In this exploratory analysis, researchers used a rank-preserving structural failure time (RPSFT) model, to quantify how treatment with APC8015F might have impacted the overall survival of the Phase 3 IMPACT trial by adjusting for the positive treatment effect of APC8015F in the control arm. The previously published intent to treat analysis, which is described in the Food and Drug Administration (FDA) approved prescribing information for PROVENGE, did not account for cross-over and demonstrated a 4.1 month median survival benefit (HR=0.775, 95% CI: 0.614, 0.979). Using the RPSFT model, and assuming that APC8015F was equally effective as PROVENGE, the median overall survival benefit of PROVENGE in the Phase 3 IMPACT trial was estimated to be 7.8 months, had there been no cross-over to APC8015F (HR=0.60, 95% CI: 0.41, 0.95).“The results of this exploratory analysis are encouraging,” said Chadi Nabhan, MD, Oncology Specialists S.C., Lutheran General Hospital Cancer Care Center. “These data continue to support the use of PROVENGE as an important and compelling treatment option for men with certain types of advanced prostate cancer.” Abstract #42 : Sipuleucel-T Product Characterization Across Different Disease States of Prostate Cancer An exploratory analysis of several PROVENGE clinical trials (IMPACT, ProACT, OpenACT, and NeoACT) examined the product characteristics of PROVENGE comparatively across different disease states (asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC), and mCRPC, and neoadjuvant). The pattern of antigen presenting cell (APC) activation, as measured by upregulation of CD54, was consistent across all of the clinical trials, with increased APC activation at the second and third PROVENGE treatments relative to the first. The second and third dose of PROVENGE also consistently showed enhanced expression of lymphocyte activation markers and cytokines. APC activation tended to be more robust in earlier disease states, as evidence by increased cumulative fold increase in CD54 upregulation in neoadjuvant patients (35.5) relative to asymptomatic or minimally symptomatic mCRPC (28.7) and mCRPC patients (21.8; P<0.0001).
“I find these data to be very compelling – this exploratory analysis provides insight into the biological effect of PROVENGE and immunologic activity across different stages of prostate cancer,” said Eric Small, MD, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center. “These data suggest that PROVENGE should be studied in earlier stages of disease, when patients have less tumor burden.”Abstract #181 : Neoadjuvant Sipuleucel-T in Patients with Localized Prostate Cancer: Immune Responses in Prostate Tumor Tissue A Phase 2 study, called NeoACT (NEOadjuvant Active Cellular immunoTherapy), evaluated treatment with PROVENGE prior to radical prostatectomy in patients with localized prostate cancer. PROVENGE is not currently indicated in this setting. This analysis assessed the presence of lymphocytes by immunohistochemistry (IHC) in radical prostatectomy tissue following treatment with PROVENGE and compared it to prostate biopsy tissue obtained prior to treatment. At the time of abstract submission, IHC analysis had been completed in 19 patients. Significant increases (>2-fold) in CD3 + and CD4 + T-cells populations were observed at the tumor rim between the interface of benign and malignant tissue when compared with the pretreatment biopsy tissue (ANOVA post hoc Newman-Keuls test: P=0.0002, both). “This analysis of prostate tissue from patients participating in the Phase 2 NeoACT trial demonstrated increased T-cell activity at the rims of prostate cancer tumors, which provides important support for PROVENGE’s intended mechanism of action,” said Lawrence Fong, MD, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center. Abstract #178 : Evaluation of Immune Activation Following Neoadjuvant Sipuleucel-T in Subjects with Localized Prostate Cancer In addition, a second analysis of the Phase 2 NeoACT study evaluated immune activation in PROVENGE for patients with localized prostate cancer treated prior to surgery. This analysis evaluated the cellular composition and APC activation of the product both prior to and after the culture with the recombinant fusion protein PA2024, consisting of prostatic acid phosphatase (PAP) and granulocyte macrophage colony stimulating factor (GMCSF).
The Phase 2 NeoACT study enrolled 42 patients and 38 received all three infusions of PROVENGE. Consistent with past findings in PROVENGE mCRPC trials, CD54 upregulation (APC activation) was greater at the second and third PROVENGE infusions. The expression of early T-cell activation markers (CD134, CD137, CD278 and CD279) was increased in cells obtained after the first infusion of PROVENGE, and then further increased post-culture with PA2024. Also observed was a progressive increase in memory B-cells (CD20 +CD27 +IgD -CD86 +; pre- and post-culture) and activated mature B-cells (CD20 +CD27 +IgD +CD86 +; post-culture) following the first infusion of PROVENGE. Activated T-cell-associated cytokines were significantly elevated (TNF-α, P < 0.001; IFN-γ, P < 0.001; and IL-2, P < 0.001) in the second and third PROVENGE doses.Initial results from the trial indicate neoadjuvant treatment with PROVENGE showed evidence of immune system activation that included APCs, memory and activated mature B-cells, and both CD4 + and CD8 + T-cells. This analysis supports further studies to evaluate the use of PROVENGE in localized prostate cancer. About the IMPACT Trial IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment) is a 512-patient, multi-center, randomized, double-blind, controlled study evaluating men with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. The primary endpoint was overall survival. Initial results from the IMPACT study found PROVENGE extended median survival by 4.1 months compared to control (25.8 months vs. 21.7 months) and reduced the risk of death by 22.5 percent compared to control. Control used in the trial was non-activated autologous peripheral blood mononuclear cells. The survival benefit associated with PROVENGE was observed consistently across multiple patient subgroups, including those with prognostic factors known to be adversely correlated with overall survival, such as PSA, LDH, alkaline phosphatase, number of bone metastasis, Gleason score, performance status, and presence of pain. Adverse events more commonly reported in the PROVENGE arm of this study included chills, fever, headache, influenza-like illness, muscle aches, hypertension and groin pain.
PROVENGE Indication and Important Safety InformationPROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. PROVENGE is intended solely for autologous use and is not routinely tested for transmissible infectious diseases. The safety evaluation of PROVENGE was based on 601 prostate cancer patients in four randomized clinical trials who underwent at least one leukapheresis. The most common adverse events (incidence greater-than or equal to 15%) are chills, fatigue, fever, back pain, nausea, joint ache, and headache. Serious adverse events reported in the PROVENGE group include acute infusion reactions (occurring within 1 day of infusion) and cerebrovascular events. In controlled clinical trials, 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. To fulfill a post marketing requirement and as a part of the company's ongoing commitment to patients, Dendreon will conduct a registry of approximately 1500 patients to further evaluate a small potential safety signal of cerebrovascular events. In four randomized clinical trials of PROVENGE in prostate cancer patients, cerebrovascular events were observed in 3.5% of patients in the PROVENGE group compared with 2.6% of patients in the control group. For more information on PROVENGE, please see the full prescribing information at http://www.provenge.com or call 1-877-336-3736. About Dendreon Dendreon Corporation is a biotechnology company whose mission is to target cancer and transform lives through the discovery, development, commercialization and manufacturing of novel therapeutics. The Company applies its expertise in antigen identification, engineering and cell processing to produce active cellular immunotherapy (ACI) product candidates designed to stimulate an immune response in a variety of tumor types. Dendreon's first product, PROVENGE® (sipuleucel-T), was approved by the FDA in April 2010. Dendreon is exploring the application of additional ACI product candidates and small molecules for the potential treatment of a variety of cancers. The Company is headquartered 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. This news release contains forward-looking statements that are subject to risks and uncertainties. Factors that could affect these forward-looking statements include, but are not limited to, developments affecting Dendreon's business and prospects, including progress on the commercialization efforts for PROVENGE. 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 www.sec.gov . Dendreon cautions investors not to place undue reliance on the forward-looking statements contained in this press release. All forward-looking statements are based on information currently available to Dendreon on the date hereof, and Dendreon undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this press release, except as required by law.