Sipuleucel-T (PROVENGE?, Dendreon Corporation), an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone-refractory) prostate cancer (CRPC) has been approved by the FDA for the treatment of men with advanced prostate cancer in the US. Sipuleucel-T is designed to induce an immune response against prostatic acid phosphatase (PAP), an antigen expressed in most prostate cancers, and is the first in a new therapeutic class known as autologous cellular immunotherapies.

The FDA approval of Sipuleucel-T is a testament to the courage of the patients and researchers who participated in our studies and is the culmination of nearly 15 years of research and development by our dedicated employees,” said Mitchell H. Gold, M.D., president and chief executive officer of Dendreon. “The approval of PROVENGE is a significant step towards realizing our mission of transforming the lives of patients with cancer, and it also marks Dendreon’s transformation into a commercial enterprise, ready to support the successful launch of the first personalized treatment for cancer.”

Prostate Cancer Kills
According to the American Cancer Society, prostate cancer is the most common non-skin cancer in the United States and the third most common cancer worldwide. More than two million men in the United States have prostate cancer, with an estimated 192,280 new cases and approximately 27,360 men expected to die from the disease in 2009.

Active Cellular Immunotherapy
Sipuleucel-T is classified by the FDA as an autologous cellular immunotherapy. It is designed to be an active cellular immunotherapy. Active cellular immunotherapy is designed to stimulate a T-cell response to cancer cells. An immune response is started by a specialized class of immune system cells called antigen-presenting cells (APCs). APCs take up antigen from their surroundings and process the antigen into fragments that are then displayed on the APC surface. Once displayed, these antigens can be recognized by specific classes of immune cells called T lymphocytes (T-cells), which are activated as a result of their engagement with APCs and combat disease by seeking antigen-bearing cells directly. PROVENGE is designed to target the prostate cancer antigen prostatic acid phosphatase (PAP), an antigen that is expressed in more than 95 percent of all prostate cancers.

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Dendreon, the manufacturer of the new drug, intends to make sipuleucel-T available through approximately 50 centers, all of which were approved sipuleucel-T clinical trial sites, and expects to increase capacity over the next year. The increased capacity will be a result of the anticipated licensure of its expanded New Jersey, Atlanta, Georgia and Orange County, Calif. facilities in mid-2011.

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“The approval of PROVENGE, the first autologous cellular immunotherapy, represents a significant scientific and clinical advancement for the treatment of prostate cancer,” said Philip Kantoff, M.D., Director of the Lank Center for Genitourinary Oncology, Chief of the Division of Solid Tumor Oncology, and Chief Clinical Research Officer at Dana-Farber Cancer Institute, Professor of Medicine at Harvard Medical School. “Cancer immunotherapies that use the patient’s own immune system will likely create an entirely new treatment paradigm for patients with cancer.”

Clinical Trial Results Supporting FDA Approval
Three Phase 3 studies involving 737 patients were submitted to FDA to support licensure. The pivotal study was the Phase 3 IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment) trial (D9902B), a 512-patient, multi-center, randomized, double blind, placebo-controlled study that evaluated men with asymptomatic or minimally symptomatic, metastatic CRPC. sipuleucel-T extended median survival beyond two-years, demonstrating a median improvement of 4.1 months compared to the control group (25.8 months versus 21.7 months). Overall, sipuleucel-T reduced the risk of death by 22.5 percent compared to the control group (HR=0.775). Results from the similarly designed Study D9901 in asymptomatic metastatic CRPC also demonstrated a survival advantage of similar clinical magnitude as the IMPACT study.

“The approval of PROVENGE represents a significant advancement in the care of men with advanced prostate cancer. PROVENGE offers a new choice in the front line treatment for these men who – until today – had few appealing treatment options,” said David Penson, M.D., Professor of Urologic Surgery at Vanderbilt University Medical Center.

Sipuleucel-T is intended solely for autologous use and is not routinely tested for transmissible infectious diseases. The safety evaluation of sipuleucel-T was based on 601 prostate cancer patients in four randomized clinical trials who underwent at least one leukapheresis procedure. The most common adverse events (incidence >= 15%) are chills, fatigue, fever, back pain, nausea, joint ache, and headache. Serious adverse events reported in the sipuleucel-T 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 sipuleucel-T 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 Sipuleucel-T 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 sipuleucel-T in prostate cancer patients, cerebrovascular events were observed in 3.5% of patients in the sipuleucel-T arm compared with 2.6% of patients in the control arm.

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