Our STN: BL 125197/0
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.
Raj K. Puri, M.D., Ph.D.
Division of Cellular and Gene Therapies
Office of Cellular, Tissue, and Gene Therapies
Center for Biologics Evaluation and Research