

Clinical Team Leader Review Memo Regarding SGE Patient Representative - 
Provenge, April 26, 2010


 
Background: PROVENGE® (Sipuleucel T, APC8015) is an autologous cellular 
immunotherapy product consisting of peripheral blood mononuclear cells (PBMCs) 
obtained from patients by leukapheresis and activated in vitro with a 
recombinant fusion protein (prostatic acid phosphatase fused with GM-CSF). A BLA 
was submitted, based on survival advantages observed in 2 randomized studies of 
asymptomatic or minimally symptomatic, metastatic, castrate resistant (hormone 
refractory) prostate cancer. Study 9902B enrolled 512 subjects: 341 subject in 
the sipuleucel-T arm and 171 subjects in the placebo arm. The primary analysis 
showed a statistically significant difference in overall survival favoring the 
sipuleucel-T arm; the difference in median survival times was 4.1 months (25.8 
months vs. 21.7 months) in favor of sipuleucel-T.  The safety of sipuleucel-T 
was evaluated in 904 patients randomized 2:1 in four blinded, placebo-controlled 
studies. Overall, treatment was relatively well tolerated: chills, fatigue, 
pyrexia, back pain, and nausea were the most common AEs. A possible increased 
risk of stroke was noted.

FDA has initiated a program of incorporating patient representative special 
government employees as advisors to FDA during the review process through the 
Office of Special Health Issues (OSHI) in the Office of the Commissioner. Mr. 
Jim Kiefert of Tucson, Arizona is an SGE for prostate cancer applications who 
was recommended by OSHI and cleared for receipt of confidential proprietary 
information. He was evaluated for of COI by the CBER Advisory Committee 
Executive Secretary and cleared for participation.

Mr. Kiefert was provided with the sponsor’s study report and draft label and 
participated in 2 teleconferences with the clinical review team, on February 8, 
2010 and again on April 25, 2010. Mr. Kiefert provided general advice regarding 
the indication statement, labeling, and patient instructions on the label and 
the clinical benefit noted in the study report. He indicated that he thought 
stroke was an important risk to patients. FDA will require the sponsor to 
complete a post marketing study to evaluate the risk of stroke in patients who 
receive sipuleucel-T.
 

   