BETHESDA, MarylandMembers of the Oncologic Drugs Advisory Committee (ODAC) unanimously recommended that the Food and Drug Administration delay considering the approval of Orplatna (satraplatin, GPC Biotech) until the agency receives overall survival data from the ongoing SPARC clinical trial.
GPC Biotech had sought accelerated approval for its drug for the treatment of hormone-refractory (androgen-independent) prostate cancer (HRPC) that had failed prior chemotherapy on the basis of findings from a protocol-specified preliminary analysis that showed a 33% reduction in the risk of disease progression (reported in Oncology NEWS International March 2007, page 1).
[Editors' Note: A week after the meeting, GPC Biotech announced that it had withdrawn its New Drug Application (NDA) for Orplatna due to the ODAC decision. The company anticipates overall survival results to be available within 6 months. "However, this timing is based on an extrapolation of death rates in the trial and may change," GPC Biotech said in a press release. Bernd R. Seizinger, MD, PhD, CEO of GPC Biotech, commented: "We are focusing our efforts on the overall survival results from SPARC and integrating these data into the strongest possible NDA submission. If these data are positive, we plan to submit an NDA as quickly as possible."]
The ODAC panel examined five signifi-cant issues raised by FDA about the Orplatna NDA (Table) and sought answers from company executives before the 13-to-0 vote. In their questions and discussions, members made clear their concerns with several aspects of the study.
A key issue was whether the Orplatna endpoint data presented served as an adequate surrogate likely to predict that the drug will increase overall survival. "We need to know that," John T. Farrar, MD, of the University of Pennsylvania and a temporary voting member of the panel, told the sponsor. "We don't know now that long-term treatment won't lead to something else, kidney failure or other things, that would lessen survival."
The final survival analysis will take place after 700 deaths occur. In May, GPC Biotech officials notified FDA that they expected to have the survival data by the end of 2007. However, Marcel Rozencweig, MD, the company's chief medical officer, told ODAC that deaths among SPARC participants had slowed to five or fewer per month. "If that trend continues, it is going to take much longer to reach the 700 events," he said.
Richard Pazdur, MD, director of FDA's Office of Oncology Drug Products, cautioned the committee that "this time difference should not be the tie breaker" in the panel's decision whether to advise FDA to delay approval consideration until it has the survival findings.