The road from drug testing to approval is never smooth.
Recent case in point: satraplatin, a new oral chemotherapy for prostate cancer being developed by
Good results presented Friday from a phase III clinical trial suggested a relatively easy approval for satraplatin both here and in Europe.
But a more detailed look at the drug over the weekend has raised worries that prostate cancer patients may not live longer after taking satraplatin. This could complicate the approval process, especially in Europe, and limit the drug's commercial appeal.
Pharmion controls European rights to satraplatin and will be responsible for seeking approval there later this year. Munich-based GPC Biotech, which trades primarily on the Frankfurt exchange, controls the drug's U.S. rights. An approval filing to the FDA was submitted on Feb. 16. If the FDA accepts the satraplatin application for priority six-month review, a decision could come in mid-August.
The other company affected by satraplatin's fate is
, which out-licensed the drug to GPC Biotech in return for cash milestones and a low-double-digit royalty on worldwide sales.
Satraplatin is the first oral (pill) form of the platinum class of intravenous chemotherapy drugs, which exceeded $2 billion in sales in 2005. GPC Biotech is in charge of satraplatin's clinical development, focused first on men with advanced prostate cancer who have already failed first-line chemotherapy treatment.
Results from a phase III study were positive, showing that satraplatin plus the steroid prednisone significantly reduced the risk of disease progression by 33% compared to patients given prednisone and placebo.
This result was statistically highly significant. At the median, progression-free survival, or PFS, for satraplatin patients was 11.1 weeks compared with 9.7 weeks for the control arm, a modest difference of only 14%. However, this difference increased over time. At the 75th percentile, the PFS benefit shot up to 81% in favor of satraplatin.
Men with this latter stage of prostate cancer tend to be older and relatively frail, but satraplatin, as a pill, was well tolerated with an acceptable safety profile.
This data was presented Friday at a prostate cancer conference in Orlando sponsored by the American Society of Clinical Oncology. There are currently no approved drugs for men with this late stage of prostate cancer (although other drugs are used off-label), so satraplatin might expect a fairly easy approval. From a commercial perspective, satraplatin peak sales in prostate cancer could reach the $400 million range in the U.S., a bit less in Europe.
But you can't assume anything will be easy when it comes to drug development. Satraplatin is no exception.
In the phase III study, the PFS endpoint used to define the drug's clinical benefit was actually a composite of several endpoints. These included death, symptomatic pain, growth of tumors picked up by X-ray or MRI, skeletal events like bone fractures or decreased performance status.
A separate analysis of the satraplatin clinical trial handed out at the prostate cancer meeting this weekend broke down the drug's efficacy into the aforementioned individual components -- and revealed some worrisome details. On a percentage basis, more satraplatin patients "progressed" because of death, compared with patients in the control arm. And the only component listed above where satraplatin performed significantly better than the control arm was in the reduction of symptomatic pain.
Why is this a potential problem? Because it suggests that satraplatin's primary benefit might be as a pain reliever for these very ill prostate cancer patients, and not as a drug that necessarily helps them live longer.
Of course, pain reduction, especially in prostate cancer, is not an insignificant clinical benefit for patients. But in Europe, drug regulators are sticklers for cancer drugs with proven survival benefits, so Pharmion might have a tougher time getting satraplatin approved there.
In the U.S., the FDA prefers cancer drugs that improve survival, but it's certainly not a requirement for approval. And before starting its phase III study of satraplatin in prostate cancer, GPC Biotech reached an agreement with the FDA that progression-free survival -- and not overall survival -- would be an approvable endpoint for the drug.
But drug approval doesn't always translate into big sales. If oncologists look at satraplatin's profile and don't see a survival benefit, or merely view the drug as a palliative treatment, they may not prescribe it much for their prostate cancer patients. Likewise, GPC Biotech might not be able to price the drug as richly as they'd like (or they might run into problems with insurance reimbursement).
GPC Biotech spokeswoman Laurie Doyle says the breakdown of the progression-free survival endpoint, particularly the imbalance in death progressions, does not necessarily say anything about satraplatin's ability to prolong survival in these patients. Last September, in fact, an interim analysis of the study was conducted showing satraplatin patients were living longer, although the difference compared with control patients was not statistically significant.
Doyle says an updated analysis of the survival in the satraplatin trial will be conducted and released in the fall of this year. At this point, she adds, the company is hopeful that satraplatin will show a survival advantage, but given the unmet medical need for these prostate cancer patients, GPC Biotech doesn't believe it's necessary for the drug's approval.
Shares of Pharmion slipped 1% amid the market's heavy selloff Tuesday, closing at $26.31.
Adam Feuerstein writes regularly for RealMoney.com. In keeping with TSC's editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet.com. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback;
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