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FDA Approval for Sipuleucel-T

Brand name: Provenge®

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.

On April 29, 2010, the Food and Drug Administration (FDA) approved sipuleucel-T (PROVENGE®, made by the Dendreon Corporation), an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer.

Sipuleucel-T is a cellular immunotherapy consisting of autologous peripheral blood mononuclear cells (PBMCs), obtained by leukapheresis and cultured (activated) with a recombinant human protein (PAP-GM-CSF) consisting of prostatic acid phosphatase linked to granulocyte-macrophage colony-stimulating factor.

This approval was based on results from a randomized double-blind placebo-controlled multicenter trial (Study 9902B).  Overall survival (OS) was the primary efficacy endpoint of this trial.  Eligible patients had metastatic disease in soft tissue and/or bone with evidence of disease progression determined at either of these sites or by serial measurement of prostate specific antigen (PSA).  All patients had prior adequate hormonal therapies with castrate testosterone levels attained.  Patients with liver, lung, or brain metastases were excluded from the trial. Patients who reported moderate to severe prostate cancer-related pain and/or use of narcotics for cancer-related pain were also excluded.  Patients were randomly assigned to receive either the sipuleucel-T treatment or a control (peripheral blood mononuclear cells that were not activated).  Patients in both groups underwent three leukapheresis procedures (approximately Weeks 0, 2, and 4), followed 3 days later with an infusion of either sipuleucel-T or the non-activated control treatment.  Patients who had disease progression during the trial were treated at the physician’s discretion.

Five hundred twelve patients were randomly assigned (2:1) to either sipuleucel-T (n=341) or the control treatment (n=171).  Eighty-two percent had received prior combined androgen blockade; 54 percent received local radiotherapy; 35 percent underwent radical prostatectomies; 18 percent had prior chemotherapy, including docetaxel. The median age was 71 years (range 40-89); 90 percent of patients were Caucasian. 

Patients treated who received sipuleucel-T had a median OS of 25.8 months compared to 21.7 months for patients who received the control treatment (p= 0.032, HR 0.775, 95 percent CI 0.61, 0.98).  There was no difference in time-to-progression.  Fifty-seven percent of patients who received sipuleucel-T and 50.3 percent of patients who received the control treatment received docetaxel after disease progression.

A second trial (Study 9901) provided supportive evidence to the results of Study 9902B. Study 9901 was a smaller, randomized double-blind placebo-controlled multicenter trial of 127 patients with metastatic, castrate resistant prostate cancer. Patients were randomly assigned (2:1) to receive either sipuleucel-T (n = 82) or control (n = 45).  The primary endpoint was time-to-disease progression.  All patients were followed for OS, although the method of survival analysis was not pre-specified.  Analysis of the primary endpoint did not reach statistical significance.  The median OS of patients treated with sipuleucel-T was 25.9 months compared to 21.45 months for patients treated with the control.

Common adverse reactions reported during a safety evaluation of 601 patients who received sipuleucel-T were chills, fatigue, fever, back pain, nausea, joint ache, and headache.  The majority of adverse reactions were mild or moderate in severity.  Severe adverse events occurred in 23.6 percent of patients who received sipuleucel-T compared to 25.1 percent of patients who received the control.  Life-threatening adverse events were observed in 4.0 percent of patients who received sipuleucel-T compared to 3.3 percent of patients who received the control.  Fatal adverse events occurred in 3.3 percent of patients who received sipuleucel-T compared to 3.6 percent of patients who received the control.  Serious adverse reactions that were reported more frequently in patients receiving sipuleucel-T compared to patients receiving the control included acute infusion reactions and stroke.

This summary was provided by Celia Witten, M.D., director of FDA's Center for Biologics Evaluation and Research (CBER), Office of Cellular, Tissue and Gene Therapies (OCTGT).

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

  • Updated: July 3, 2013