That whooshing sound you heard on Friday was shares of GPC Biotech (NASDAQ:GPCB) falling 25%. The drop occurred following the FDA release of its briefing document (link opens a PDF) for an upcoming advisory committee hearing on GPC's lead drug, Satraplatin.
Satraplatin is scheduled for an FDA PDUFA review in August. Before this review of GPC's marketing application for Satraplatin, an advisory panel to debate the drug will be held tomorrow. The purpose of the briefing document released on Friday was to outline the FDA's concerns and thoughts on the drug and to help direct the advisory panel discussions.
GPC licensed Satraplatin from Spectrum Pharmaceuticals (NASDAQ:SPPI) in 2002 and then out-licensed the European -- and many other countries' -- rights to Pharmion (NASDAQ:PHRM) in 2005.
FDA goes "boo!" and investors runWhat caused the negative reaction in shares of GPC on Friday was that in the briefing document, the FDA expressed concerns about one of the co-primary endpoints in the pivotal 950-person Satraplatin phase 3 study.
In determining whether patients in the pivotal study had experienced progression-free survival (i.e. the patient staying alive and the cancer not spreading), GPC included some non-standard definitions of progression-free survival, like patient pain progression, rather than just the more traditional radiologic review of the tumor site that most oncology drugmakers use when monitoring cancer progression in clinical studies.
Even normal PFS data is prone to subjectivity by doctors reviewing the x-rays, for example, but the two reviewers of the patient data in the drug's phase 3 study disagreed on whether patients had experienced tumor progression nearly 40% of the time.
The FDA never looks fondly on dirty or disputed data and stated in the briefing document that this discrepancy "raises the question whether progression could be reliably assessed in this trial." Other oncology compounds like Amgen's (NASDAQ:AMGN) Vectibix have been approved based mainly on PFS survival data (even from smaller studies) but with more traditional definitions of PFS used in their pivotal studies.
The FDA had several other important issues with GPC's PFS endpoint. If GPC had just defined a standard progression-free survival endpoint (via solely radiologic review) as the primary endpoint, then the drug's approvability would be less in doubt now. In fact, Satraplatin was very successful on this traditional definition of PFS, with patients treated with the drug experiencing 36 weeks of PFS compared to only 20 weeks for patients on placebo.
The other big negativeEven though GPC's PFS data may have some holes in it, the data still looks strong. Post-hoc subgroup analyses that the FDA included in its briefing document fail to find many faults with the drug's efficacy despite the agency's mission to dissect the data in a critical fashion.
Since the agency's reviewer of the Satraplatin data does have the above-mentioned potential issues with the PFS endpoint, the most conservative step that members of the advisory panel might take tomorrow is to recommend marketing approval only if successful data on the co-primary endpoint of overall survival comes in.
The overall survival assessment of the phase 3 study is expected to be completed by the end of 2007. The benefit to waiting, from the FDA's perspective, is that it could avoid an embarrassing situation like with AstraZeneca's (NYSE:AZN) Iressa. Here, the compound was approved based on one set of data, but later the drug failed to show an improvement in survival and had to be partially withdrawn from the market.
Even if the FDA does delay full Satraplatin approval, investors can take some solace that an interim analysis of overall survival completed in 2006 showed a positive trend (not statistically significant) favoring Satraplatin in the phase 3 study.
Is a negative advisory panel vote on its way?
GPC is seeking to market Satraplatin for use after prostate cancer patients have failed other chemotherapy drugs. Choosing to go for approval as a second-line indication may be an advantage for GPC and make the FDA a little less reluctant to approve the compound, since late-stage prostate cancer patients have no approved treatment options if first-line chemotherapeutics like Sanofi-Aventis' (NYSE:SNY) Taxotere fail to be effective.
The FDA can be very rigid when it looks at statistical data sometimes. The hesitation expressed by the agency in the Satraplatin briefing document surprised me and increases the odds that the advisory panel will recommend waiting to approve the drug until the overall survival data comes in.
I still think that Satraplatin will ultimately be approved, but the likelihood that the agency grants an approvable letter in August when the drug's regulatory review is scheduled to occur just went up. The other possibility is that the FDA approves the drug and then requires positive survival data for its continued marketing.
As the Satraplatin phase 3 study data proves, no clinical trial is perfect. Compared with the data package that Dendreon (NASDAQ:DNDN) presented in an advisory panel in March for its lead drug Provenge, the Satraplatin study results are superior.
Dendreon received a positive advisory panel vote on the efficacy and safety of Provenge, and my bet is that GPC will achieve at least the same outcome on Tuesday. When the advisory panel transcript is posted, investors should pay careful attention to what the panel has to say about the PFS endpoint -- its words on that topic will give the biggest hint as to whether GPC can get marketing approval in August.
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Fool contributor Brian Lawler does not own shares of any company mentioned in this article. The Fool has a disclosure policy.
