

Letter to Dendreon Corporation - Provenge, February 26, 2007



 
Our STN:  BL 125197/0
Dendreon Corporation
Attention:  Elizabeth C. Smith
Vice President of Regulatory Affairs
3005 First Avenue
Seattle, WA 98121

Dear Ms. Smith:

We are reviewing your biologics license application (BLA) dated November 9, 2006 
for Sipuleucel-T and have the following comments:

“For most products, routine pharmacovigilance (i.e., compliance with applicable 
postmarket reporting requirements under FDA regulations) is sufficient for 
postmarketing risk assessment.  As outlined in Guidance for Industry: Good 
Pharmacovigilance Practices and Pharmacoepidemiologic Assessment 
(http://www.fda.gov/Cder/guidance/6359OCC.htm), FDA believes pharmacovigilance 
plans may be appropriate when: (1) serious safety risks have been identified 
pre- or post-approval, or (2) at-risk populations have not been adequately 
studied.  The pharmacovigilance plan is specifically focused on detecting new 
safety risks and/or evaluating already identified potential safety risks.

Outcomes in Non-Caucasian Patients

Ten African-American (AA) subjects received sipuleucel-T in the pivotal trials. 
The latest figures available from NCI’s Cancer Statistics Review (2003) indicate 
that AA men have a markedly higher annual incidence rate of invasive prostate 
cancer than Caucasian patients (247 vs. 160 per 100,000). The AA population may 
also have a poorer prognosis for reasons that are not yet established. As 
pointed out in the BLA, the low number of non-Caucasian enrollees precludes an 
assessment of safety or efficacy in this population.

Because it is questionable whether trial outcomes for Caucasian patients can be 
extrapolated to other groups, we recommend that you begin now to develop a 
pharmacovigilance plan for implementation if the product is licensed.  We 
suggest that you consider a registry to capture disease characteristics (such as 
stage, grade), clinical status at enrollment, and race/ethnicity of all 
consenting patients. Inclusion of sufficient identifiers (ideally first and last 
name, date of birth and social security number) would then allow assessment of 
survival with use of the National Death Index for patients otherwise lost to 
follow-up (see www.cdc.gov/nchs/ndi.htm for more details).

In deciding whether to establish this registry, we recommend that you consult 
the following two FDA Guidances: E2E Pharmacovigilance Planning 
(www.fda.gov/cber/gdlns/ichpvp.htm) and Good Pharmacovigilance Practices and 
Pharmacoepidemiologic Assessment (see link above). These Guidances include 
information about the components recommended for registry protocols and 
implementation as well as feasibility and alternative methods. Particular effort 
in the planning and design should be devoted to enrollment of the highest 
proportion of patients possible.

Additional recommendations may be forthcoming after we have completed our review 
of the BLA submission. We are offering this preliminary recommendation now in 
order to allow maximal time for development of your Pharmacovigilance Plan.”

If you have any questions, please contact the Regulatory Project Manager, Lori 
Tull, at (301) 827-5102.

Sincerely yours,

Raj K. Puri, M.D., Ph.D.
Director       
Division of Cellular and Gene Therapies      
Office of Cellular, Tissue, and Gene Therapies
Center for Biologics Evaluation and Research
 
