Wednesday, October 31, 2007

Nail in the Coffin for GPC?

Turns out FDA’s ODAC committee had a point when it announced, in July, that it would wait for overall survival (OS) data from GPC Biotech’s prostate cancer drug satraplatin (Orplatna) before considering review. Topline OS data—released today, sooner than expected—was negative. It wasn’t as if the p value just missed, either: it was 0.8. Median survival in the placebo arm was if anything a little longer than that in the treatment arm.

At the time, there were cries of despair: refusing to consider interim data around progression-free survival marked the FDA’s new ultra-conservative stance, noted some analysts, as we reported here. This was the end of accelerated approval.

Now the story looks rather different. This time it’s only about GPC—and whether it has a future. The overall survival data, one analyst predicted to IN VIVO Blog in July, “will decide the fate of the company, not just satraplatin.” Indeed, the ODAC decision to hang approval on a single end-point, rather than consider interim progression-free survival data as well, turned it into a make or break event for the company.

So is this the end of GPC? It’s not clear yet—we’ll find out more on the conference call scheduled today at 12.30 GMT. GPC’s shares lost over 60% first thing this morning, to add to the hammering they took in the summer. As your blogger blogs, analysts are downgrading the stock to sell on questions around long-term viability. Management's credibility, already shaken by the events in July, will probably be in tatters.

Indeed, given strong interim data, the accelerated approval granted by FDA in April 2007 (hah! what use now) and GPC officers’ general confidence, some analysts before today felt that the chances of good overall survival data were reasonable. For them it was a question of re-adjusting their time-lines for approval and questioning whether GPC could afford to maintain its full clinical program for satraplatin.

Today’s release looks more like a nail in the coffin for satraplatin. When GPC withdrew its NDA following the ODAC decision, it didn’t expect overall survival data to be available until 2008; a spokeswoman told us in July that top line data would take six months to collect. Yet sooner than that, GPC is announcing a “re-evaluation of the development plan”, the negative impact on satraplatin’s EU review led by partner Pharmion, and an almost valedictory 'thank you' to those taking part in the blighted trial.

Even if GPC could afford to continue developing the drug in other indications, would it (or a potential acquiror) want to? The drug's patent life is relatively short--to 2015 with extensions, according to one London-based analyst. As for potential acquisition, the shareholder suit filed against GPC in July--accusing the company of using "improper methods" to measure satraplatin's effectiveness--pretty much guards against that.

So to the lessons (yes, always a lesson or two): partner your drug before Phase III (look, after all, at the value of proof-of-concept stage deals!). Hedge your bets. Don’t get too excited about your wonder-drug’s approvability, even if the need is unmet. Diversify--not so much as to lose the plot, but enough to avoid this sort of thing. And, ok, this time FDA looks justified in having asked for overall survival data as proof that the drug does indeed have some beneficial effect. But that still doesn’t mean the agency’s any better disposed towards cancer drugs developed by small biotechs. In fact, the satraplatin saga is only likely to have made FDA warier still of early approval based on interim analyses.

UPDATE: There wasn't a lot of new information on the conference call. GPC CEO Bernd Seizinger, MD, PhD, noted that while there are upwards of 20 subgroups of patients still to be analyzed, he didn't want to raise anyone's hopes that a subgroup analysis could trump today's bad news in any way. He also flagged up GPC's November 8th third quarter results as a time when the company would be more prepared to discuss its strategies with regards to sataplatin as well as its corporate future.

GPC still considers satraplatin an asset of value--a "Phase II asset," Seizinger said. Finally, he noted, this is "certainly not the end of GPC biotech. We have a strong cash position and an excellent team , and we still have important assets in the company." The market may be disagreeing. The stock is down about 62%, valuing the company dangerously close to its cash position, which was €93.1 million ($134 million) as of the end of June 2007.

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