May 16, 2012--Dendreon Corporation (NASDAQ:DNDN)
today announced the following PROVENGE® (sipuleucel-T) data will be
presented at the American Society of Clinical Oncology (ASCO) Annual
Meeting taking place June 1-5, 2012 in Chicago, Illinois.
"Overall Survival (OS) Benefit with Sipuleucel-T by Baseline PSA; An
Exploratory Analysis from the Phase 3 IMPACT Trial," abstract #4684.
General Poster Session, Genitourinary Cancer from 8:00 a.m. to 12:00
p.m. CT on Sunday, June 3, 2012.
"Evaluation of Immune Activation Following Neoadjuvant Sipuleucel-T in
Subjects with Localized Prostate Cancer," abstract #2563.
General Poster Session, Genitourinary Cancer from 8:00 a.m. to 12:00
p.m. CT on Monday, June 4, 2012.
"Neoadjuvant Sipuleucel-T in Localized Prostate Cancer: Effects on
Immune Cells within the Prostate Tumor Microenvironment," abstract
#2564. General Poster Session, Genitourinary Cancer from 8:00 a.m. to
12:00 p.m. CT on Monday, June 4, 2012.
"Correlation of Increased Eosinophil Count Following Sipuleucel-T
Treatment with Outcome in Patients (pts) with Metastatic
Castrate-Resistant Prostate Cancer (mCRPC)," abstract #4650. General
Poster Session, Genitourinary Cancer from 8:00 a.m. to 12:00 p.m. CT
on Sunday, June 3, 2012.
"These data presented at ASCO continue to support the overall survival
benefit of PROVENGE and its mechanism of action," said Mark Frohlich,
MD, executive vice president and chief medical officer.
Abstract #4684: Overall Survival
(OS) Benefit with Sipuleucel-T by Baseline PSA; An Exploratory Analysis
From the Phase 3 IMPACT Trial
In the pivotal Phase 3 IMPACT trial, a pre-specified subgroup analysis
for baseline prognostic variables showed treatment effects consistently
favoring PROVENGE. For patients whose baseline PSA was below the median
PSA level, PROVENGE trended to demonstrate a greater treatment effect
(HR=0.685 vs. 0.865). In this most recent sub analysis, researchers
further sub-divided baseline PSA into quartiles to evaluate potential
treatment effect patterns. This exploratory analysis included all
randomized patients from the IMPACT study (n=512). Patients were
categorized by baseline PSA quartile, ECOG PS, and by median for other
baseline prognostic variables (i.e., LDH, PAP, ALP in bone-only disease,
and hemoglobin [Hgb]). Median overall survival and hazard ratio were
estimated using Kaplan-Meier and Cox models, respectively.
Results showed that an increasing baseline PSA quartile was associated
with markers of advanced disease. A consistent treatment effect was seen
in all subsets and there was a trend toward an increased magnitude of
treatment benefit in patients with a lower baseline PSA. Results for
other baseline prognostic variables also suggested a trend toward
greater benefit in subjects with better prognostic features. However,
results for baseline Hgb indicated an opposite trend.
"The results of this analysis, although not adequately powered for
significance, support an overall survival benefit with PROVENGE across
PSA quartiles," said Gerald Chodak, MD, Midwest Prostate and Urology
Health Center, Weiss Memorial Hospital. "The trend in greater magnitude
of benefit in patients with lower baseline PSA suggests that patients
with less advanced disease may benefit more from treatment with
PROVENGE, and supports the use of PROVENGE early in the natural history
of men with asymptomatic or minimally symptomatic metastatic castrate
resistant prostate cancer."
Abstract #2563: Evaluation of
Immune Activation Following Neoadjuvant Sipuleucel-T in Subjects with
Localized Prostate Cancer
In this open-label, Phase 2 NeoACT (NEOadjuvant Active Cellular
immunoTherapy) study, patients with localized prostate cancer received
three infusions of PROVENGE at approximately two-week intervals,
beginning six to seven weeks prior to radical prostatectomy. PROVENGE is
not currently indicated for neoadjuvant treatment of localized prostate
cancer. Following radical prostatectomy, subjects were randomized 1:1 to
receive / not receive a PROVENGE booster infusion 12 weeks post-radical
prostatectomy. Cellular composition, antigen presenting cell (APC)
activation, cytokines, and T and B cell activation were profiled before
and after each culture with PA2024, the fusion protein containing
prostatic acid phosphatase used to generate PROVENGE.
Of the 42 enrolled study patients, 38 received all three infusions of
PROVENGE, and 15 patients received a booster infusion. Consistent with
PROVENGE in mCRPC, CD54 upregulation (APC activation) was greater at the
second and third infusions relative to the first (P<0.001). The
expression of early T cell activation markers (CD134, CD137, CD278 and
CD279) were increased in pre-culture cells obtained after the first
infusion, and further increased after culture. Activated mature B cells
(CD20+CD27+IgD+CD86+) increased following culture in all three products (P<0.01);
memory B cells (CD20+CD27+IgD-CD86+) were progressively increased
following the first infusion (P<0.05 third vs. first product).
TNF-?, IFN- were secreted at higher levels during culture of the second
and third products (all P<0.001). The observed increases in CD54
upregulation, early T cell activation markers, and memory and activated
mature B cells were maintained at booster treatment.
Results from this analysis support further evaluation of PROVENGE in the
neoadjuvant setting based on the enhanced immune activity demonstrated
in this analysis.
"These data are exciting because PROVENGE in the neoadjuvant setting
also resulted in enhanced immune system activation that was consistent
with boosting of an immune response primed with the first infusion,"
said Lawrence Fong, MD, University of California, San Francisco Helen
Diller Family Comprehensive Cancer Center. "Immune activation was
maintained at the booster infusion three months following initial
treatment with PROVENGE. Additional studies are warranted to further
examine the importance of PROVENGE as a neoadjuvant treatment option for
men with localized prostate cancer."
Abstract #2564: Neoadjuvant
Sipuleucel-T in Localized Prostate Cancer: Effects on Immune Cells
within the Prostate Tumor Microenvironment
In addition, a second analysis, evaluated treatment with PROVENGE prior
to radical prostatectomy in patients with localized prostate cancer.
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
32 patients. Significant increases (>3-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:
"This analysis of prostate tissue from patients participating in the
Phase 2 NeoACT trial demonstrated increased T-cells at the rims of
prostate cancer tumors, which supports an immune-mediated mechanism of
action for PROVENGE," said Lawrence Fong, MD, University of California,
San Francisco Helen Diller Family Comprehensive Cancer Center.
Abstract #4650: Correlation of
Increased Eosinophil Count Following Sipuleucel-T Treatment with Outcome
in Patients (pts) with Metastatic Castrate-Resistant Prostate Cancer
This exploratory analysis assessed the potential correlation between
increased eosinophils (white blood cells), and overall survival,
prostate cancer-specific survival, and immune response following
treatment with PROVENGE. Data from three Phase 3 trials in patients with
mCRPC (Studies D9901, D9902A, and IMPACT) were evaluated and the
analysis included complete blood counts performed at baseline and at
weeks 2-34 following treatment with PROVENGE.
In patients who were treated with PROVENGE, an increase in eosinophil
counts were observed by week 6 and decreased to nearly baseline by week
14, while the eosinophil counts in the control arm remained consistent.
Of the 377 patients treated with PROVENGE and eligible for analysis, 105
(27.9%) had eosinophilia. Baseline disease characteristics associated
with eosinophilia were indicative of better prognosis (i.e., longer
Halabi predicted survival [P=0.007], lower PSA [P=0.033],
higher Hgb [P<0.001], and no prior docetaxel [P=0.012]).
In univariate analyses, eosinophilia correlated with improved overall
survival (HR=0.75; 95%CI: 0.56-1.01; P=0.057) and prostate
cancer-specific survival (HR=0.71; 95%CI: 0.53-0.97; P=0.031).
The magnitude of eosinophilia positively correlated with
antigen-specific humoral responses (P ?0.039 for wks 6, 14 and
26) and elevations in the cytokines at wk 6 (IL2 [P=0.011], IL5 [P=0.038]
and TARC [P=0.001]). AEs occurring more frequently (P<0.05)
in pts with eosinophilia were infusion-related: pyrexia (33.3 v 21.3%)
and nausea (19.0 v 10.7%). No cases of hypereosinophilic syndrome were
The analysis suggests that increases in eosinophils after treatment with
PROVENGE correlated with improved overall survival and prostate
cancer-specific survival. Larger increases in eosinophil counts were
associated with humoral responses and Th2-type cytokine production. The
analysis supports further studies to evaluate eosinophilia measurement
as a potential biomarker for PROVENGE response.
"These study findings are interesting and suggest that looking at
eosinophil count could give insight into how a patient may respond to
treatment with PROVENGE," said Douglas McNeel, MD, University of
PROVENGE Indication and Important Safety Information
PROVENGE 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.
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
Rx Mosaic Health for Dendreon Corporation