Dew and PGS - DNDN P11 Look Good:
Press Release Source: Dendreon Corporation
Dendreon Announces Preliminary Results From PROTECT (P-11) Study
Wednesday November 8, 9:00 am ET
PROVENGE Prolongs PSA Doubling Time in Patients with Early Stage Prostate Cancer
SEATTLE, Nov. 8 /PRNewswire-FirstCall/ -- Dendreon Corporation (Nasdaq: DNDN - News) today announced preliminary results from its ongoing PROTECT (P-11) clinical trial for PROVENGE® (sipuleucel-T) in patients with non- metastatic androgen-dependent (hormone sensitive) prostate cancer. The study was designed to explore the biologic activity of PROVENGE in patients with recurrent prostate cancer prior to the development of metastatic disease. The study results demonstrate a prolongation in prostate-specific antigen (PSA) doubling time (PSADT) for patients who received PROVENGE compared to placebo. PSADT is currently considered to be one of the best predictors of clinical outcome in patients with PSA recurrence following primary therapy. Dendreon plans to submit the data for presentation at a future upcoming medical meeting.
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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 PSA recurrence following surgical removal of the prostate. A total of 176 patients at 19 sites in the United States were randomized 2:1 to receive PROVENGE or placebo following a 3-month course of hormonal therapy. Patients were then followed with serial PSA measurements to evaluate the impact of PROVENGE on PSA and PSADT. 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.
Preliminary Study Results:
-- Biochemical Endpoints: As specified in the protocol, an analysis of
PSADT calculated from 90 days following randomization until biochemical
progression or the initiation of systemic therapy demonstrated that
patients randomized to receive PROVENGE had a 35 percent increase in
their PSADT compared to patients randomized to receive placebo (p-value
= 0.046). To adjust for potential variations in the rate of
testosterone recovery following hormonal therapy, the PSADT was also
calculated after a patient's testosterone returned to baseline levels.
This analysis demonstrated that patients randomized to receive PROVENGE
had a 49 percent increase in their PSADT compared to patients
randomized to receive placebo (p-value = 0.038). In addition, although
not statistically significant, there was a positive trend in the
overall delay in the time to reach a PSA level of 3.0 ng/ml for
patients in the PROVENGE arm compared to patients in the placebo arm.
-- Clinical Endpoints: There was a delay of approximately 27 percent (HR =
0.73) in the time to distant metastasis for patients randomized to
receive PROVENGE compared to patients randomized to receive placebo.
Because only 16 percent of patients in the study had a distant failure
event at the time of this analysis, it is not yet powered to evaluate
statistical significance. Per protocol, patients will continue to be
followed for the clinical endpoints of distant failure and overall
survival.
-- Immunology Data: In a subset of patients the immune response against
the recombinant antigen PA2024 was measured at baseline (before dosing
with PROVENGE or placebo) and at 4 and 13 weeks following randomization
(after dosing). PA2024 is a fusion protein composed of prostatic acid
phosphatase (PAP), and a cytokine, GM-CSF. T-cell responses were
monitored by measuring T-cell proliferation by recording the
stimulation index (SI) and by measuring the number of T-cells that
secrete interferon gamma by ELISPOT. By both methods, and at both the 4
and 13 week time points, significant responses were seen in the
PROVENGE treated patients, but not in the patients assigned to receive
placebo. For example, at 13 weeks, the median SI was 118.5 in the
PROVENGE arm compared to 2.3 in the placebo arm (p-value <0.0001). The
immune response was also monitored at the time of boosting to assess
the durability and persistence of the immune response. These analyses,
conducted at a median time of 21 months following randomization,
demonstrated that the immune response continued to persist at
significant levels (p-value <0.0001) in the PROVENGE arm compared to
the placebo arm. The median SI observed in the PROVENGE arm prior to
boosting was 93.7 and 13 weeks following a single boosting infusion of
PROVENGE, the median SI was 221.8, suggesting that the immune response
can be boosted to even higher levels.
-- Safety: Consistent with the Company's other studies conducted to date,
treatment with PROVENGE was generally well tolerated. The most common
adverse reactions associated with PROVENGE were chills, fever,
headache, fatigue and vomiting. These events were primarily low grade
events, with a short duration lasting 1 to 2 days following infusion.
"The initial results from this randomized study suggest a potential role for PROVENGE early in the natural evolution of prostate cancer," said Mark Frohlich, M.D., vice president of clinical affairs at Dendreon. "We are encouraged by the effect of PROVENGE on PSA doubling time, an important predictor of clinical outcome in this patient population. We plan on following these patients for the clinical endpoints of overall survival and time to distant failure. More importantly in the near term, the data from the patients in this study will supplement our overall safety database for PROVENGE as part of our current BLA submission for men with advanced androgen-independent prostate cancer."
