Dendreon (DNDN) Prostate Cancer Treatment PROVENGE Improves Survival

Armen Hareyan's picture
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Dendreon Corporation (Nasdaq: DNDN) announced today that it has completed the planned interim analysis of the Phase 3, randomized, double-blind, placebo-controlled IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment, also known as D9902B) clinical trial designed to assess the safety and efficacy of the investigational active cellular immunotherapy PROVENGE (sipuleucel-T) in men with metastatic androgen-independent prostate cancer. While Dendreon remains blinded to the data, the independent data monitoring committee (IDMC) reported to Dendreon a 20 percent reduction in the risk of death in the PROVENGE arm relative to placebo (Hazard Ratio= 0.80; 95% Confidence Interval [0.610-1.051]) . The IDMC observed no safety concerns and recommended that the study continue to its final analysis.

"The treatment effect we have observed in this interim analysis is consistent with that observed in the integrated analysis of our previous Phase 3 trials in this patient population when analyzed at a similar 24-month follow-up time," said Mitchell H. Gold, M.D., president and chief executive officer of Dendreon (DNDN). "Given the delayed treatment effect we have seen in previous studies, we are pleased to see evidence suggesting a prolongation of survival in the PROVENGE arm at the time of the interim analysis, as well as a favorable safety profile."

At the final analysis, which is anticipated in the middle of 2009, if the study demonstrates approximately a 22 percent reduction in the risk of death, based on 304 events, the company would expect the study to meet its primary endpoint of overall survival.

"We look forward to the final results next year and the opportunity to make PROVENGE available to the many men with advanced prostate cancer who currently have few appealing treatment options," said Dr. Gold.

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The PROVENGE IMPACT trial is a randomized, double-blind, placebo-controlled Phase 3 study which enrolled 512 men with metastatic, androgen-independent prostate cancer with a primary endpoint of overall survival. Following the U.S. Food and Drug Administration (FDA) Advisory Committee vote that there was substantial evidence of efficacy of PROVENGE and that PROVENGE was reasonably safe, the FDA requested additional clinical data to support the proposed efficacy claim. The FDA previously agreed that a positive final analysis for overall survival from the IMPACT trial would be sufficient to meet its request for additional clinical information to support the proposed efficacy claim for PROVENGE.

The hazard ratio is an estimate of the treatment effect in the treated versus the control group in a trial. The hazard ratio reported means that a PROVENGE patient who at the time of the interim analysis has 0.80 times the chance of dying compared to someone in the placebo group. Its reciprocal, 1.25, means a placebo patient has 1.25 times the chance of dying compared to someone in the PROVENGE group (this is the method that hazard ratios were reported in our previous trials).

PROVENGE may represent the first product in a new class of active cellular immunotherapies that 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. Active cellular immunotherapy holds promise because it may provide patients with a meaningful clinical benefit, such as survival, combined with low toxicity.

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 expected to be diagnosed in 2008, and approximately 28,660 men expected to die this year from the disease. Currently there are limited treatment options for men with advanced, metastatic prostate cancer.

DNDN 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 called Trp-p8 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 www.dendreon.com.

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The Unreachable Availability of Provenge Terminal patients are those who are not expected to live due to usually illness such as advanced cancer. If the patient has 6 months or less to live, those patients are considered terminally ill. Regardless, if a patient is terminal, they are without a cure or a tolerable treatment for their illness. Since such patients will likely die in a short period of time, treatment options, even if unproven, are often desired by such patients. This is understandable, because at such a severe stage of illness, such as prostate cancer, possible extension of their lives with comfort is worth it to them, regardless of lack of evidence of proof of whatever treatment that may be advantageous to them regarding these issues. The FDA, however, claims authority on the treatment options of such patients, although that administration has proven itself over the years to be rather inadequate with its frequent drug recalls and black box warnings, and they do these things only under pressure from the public, usually. So, the FDA may not be an ideal judge regarding such issues as treatment options for very sick patients. Prostate cancer is rather frequent, with between 10 to 20 percent of men predicted to acquire the disease during their lifespan, resulting in about 30,000 deaths a year from this disease. It is the third most common cancer one can acquire, and the United States has the most cases diagnosed n the world, which usually strikes men past the age of fifty. One million do have prostate cancer in the United States, and about thirty thousand will die from the disease each year. Furthermore, there are different stages of prostate cancer, and the more severe the prostate cancer cases are, the higher of what are called Gleason Scores will be, and the severe cases are the most difficult to treat, of course. Yet innovation still exists in medicine. A few years ago, a small Biotechnology company called Dendreon was working on a conceptually new treatment for the worst prostate cancer patients, and this treatment therapy created by Dendreon was named Provenge. Provenge is the first immunotherapy biologic treatment for the progressed prostate cancer patients. Usually, these patients are unresponsive to usual treatment methods for prostate cancer, and are left with chemotherapy, specifically a hazardous drug called Taxotere, as their only treatment option at such a traumatic stage of prostate cancer. Understandably, most patients at this stage refuse treatment entirely, largely due to the brutal side effects of such chemotherapy treatments as Taxodere, which include cytotoxic side effects and haematological adverse events. The immunotherapy method developed by Dendreon requires the removal of white blood cells of the diseased patient and, after altered, are re-injected into this patient now designed to attack within the diseased body what is called PAP, which is on prostate cancer cells only. This treatment requires only three such injections in a period of six weeks. This results in life extension twice that of Taxodere, and Provenge is free of the discomfort of the only other treatment of Taxotere. The medical community and survivors of prostate cancer were elated and waited with great anticipation for access to this treatment method. Fortunately, as the years passed, Provenge, by 2007, had convinced others of its safety and efficacy in its benefit for severe prostate cancer patients. This caused great joy to such patients and their families. Perhaps greater elation was experienced by the caregivers and specialists of such a disease, such as Urologists and other caregivers who treat such patients. While Provenge was on fast track status at this time at the FDA, as they at the time agreed with the benefits of this new therapy, the FDA panel recommended with clarity the approval of Provenge based on its proven and superior efficacy and safety that was demonstrated in its trials, as they announced in March of 2007. Lifespan extension of severe prostate cancer patients was twice as long with Provenge versus Taxotere, which is the only other treatment indicated for this stage of prostate cancer that had only superficial efficacy, and is free of the toxic effects of this chemotherapy agent. Now for the bad news: With great shock and surprise, the FDA agency rejected the approval of this great treatment for very sick patients due to, they said, ‘lack of data’ in May of 2007. This contradicts their favorable opinion of Provenge weeks before delivering this terrible news. Especially when one considers the FDA Commissioner is a prostate cancer survival himself! Many found this ruling completely unbelievable. Soon after this judgment was passed by the FDA, conflicts of interest were discovered by others. For example, a member of the FDA agency who was evaluating Provenge, Dr. Scher, was found to have a financial commitment to a future competitor of Provenge that was being produced by a company called Novacea, and this company had signed a co-promotion agreement with Schering to provide support for this similar prostate cancer drug treatment being developed by this company. Dr. Scher never disclosed this conflict during the approval process of Provenge. As it turns out, this anticipated prostate cancer drug made by Novacea was discovered to have serious flaws, and Schering pulled out of the agreement with Novacea. In addition to this incident and before May of 2007, baseless letters were anonymously delivered to the FDA stating negative qualities about Provenge that were without Merit and speculative claims about the treatment were fabricated in these letters, it is believed Oncologists were speculated to lobby and pressure the FDA not to approve Provenge due to anticipated revenue loss. Yet overall, the disapproval by the FDA of Provenge angered and saddened many, and a newly formed advocacy group called Care to Live filed a lawsuit against the FDA for their clear lack of etiology for not approving Provenge, as they should have, according to the data about the therapy last year. Terminal patients, I surmise, desire comfort during their progressive disease that has placed them in the last chapter of their lives, and certainly should have a right to choose any treatment that possibly could benefit them. Clearly, because of their lack of desirable and beneficial treatment options, most are willing to assume any risks of unapproved, yet potentially and likely beneficial treatments such as Provenge. Because they have a terminal illness, these benefits provided by Provenge take priority over any possible safety issues of unapproved treatments for them. The controversy could be concluded by a terminal patient signing a waiver of some sort, perhaps, stating that they are responsible for the consequences of an unapproved treatment regimen such as Provenge. Yet the FDA, with reckless disregard and with deliberate intent, denied what likely was a great treatment therapy for these very ill patients. Several have concluded that the FDA ultimately harmed others more by not approving Provenge, or offering any valid explanations explaining their action. Thier action was irrational, as one considers the agreement of the FDA and others regarding the need of the benefits provided by Provenge for the sickest of the sick with advanced prostate cancer. The FDA does in fact presently have the ability to grant what is called conditional approval for such treatment methods as Provenge at this time, and why they have not remains completely unknown. What is known is that they are accelerating and worsening the illness, an illness the FDA pledged to protect so long ago. So now the FDA appears to be a bought, corrupt, and incompetent administration without loyalty and dedication to the public and its health, but with what appears to be overt collusion with venture capitalists and corporations. This needs to be corrected in any way possible for the lives of others- regardless of their own present health state today. Because of the FDA's flaws in the past regarding drugs taken off the market along with increasing black box warnings of other drugs, which happens often with both, the individual should be the deciding factor in such matters of deciding thier treatment course presently, along with their health care provider, due to this unreliable administration called the FDA. “Facts do not cease to exist because they are ignored.” --- Aldous Huxley Dan Abshear
Why have the trials been limited to men where the cancer has metastasised? Are any trials proposed for non-metastatic cases?