Different River

”You can never step in the same river twice.” –Heraclitus

February 24, 2005

FDA Resisting Cancer Drug

Filed under: — Different River @ 7:13 pm

I’ve mentioned before, in connection with COX-2 inhibitors that for a long time, the FDA has focused too much on risks and not enough on benefits, and has implicitly assumed that the risk-benefit trade-off is the same for all patients with a given disease.

This problem is not about COX-2 inhibitors as such, its a more general FDA problem. They are delaying approval of a innovative new prostate cancer drug that works by “harnessing the body’s natural immune cells to seek out the cancer and destroy it” rather than just killing all rapidly-dividing cells and hoping it kills the cancer before the patients.

When the company first submitted its evidence to the FDA almost three years ago, asking for permission to sell it, the FDA said no. When the agency looked at all of the patients enrolled in the company’s trial, the vaccine didn’t show an overwhelming benefit in the short-term study of more than 100 prostate cancer patients. But when Dendreon looked at a smaller subgroup of the patients in the trial, those with a certain less aggressive form of prostate cancer, the results looked great. The FDA, however, does not allow “retrospective” analysis, which is statistically impure and can lead to cooked results. So Dendreon was asked to do a new trial, studying the vaccine just in patients who had the less aggressive form of the cancer. There was evidence that the vaccine worked for certain patients, but the FDA wanted more convincing data.

It turns out, however, that when Dendreon continued to follow the patients in the original study for another two-and-a-half years, the results continued to get better–for all the patients, not just those with the less aggressive cancer. Thursday evening, Dendreon announced that 34% of those who received Provenge in that original trial were still alive after three years, compared with 11% of those who took a placebo. …

Dendreon’s vaccine product seems on track to win approval, the question now is whether the FDA will wait for the company to finish the trial it has underway or approve the product based on the mounting strength of the results of that original trial. If the FDA sticks to its rules, it will wait for the new study to finish, and patients will pay a significant price: denied access to a largely safe product that looks to be a real advance in cancer care.

The problem is that at the Food and Drug Administration, creativity is not a virtue. The Agency prides itself on developing fixed approaches to regulatory problems, striving to set clear requirements on how it reviews and approves new drugs and applying these criteria consistently across its different divisions and through the review of different products in different diseases. That really stings new medical technologies like cancer vaccines, which require a different regulatory approach. One of the big problems is that patients who get the vaccines in clinical trials are less likely to benefit from these products because regulatory rules compel companies to test them on the sickest patients.

The vaccines work by stimulating the immune system to begin fighting off the cancer on its own. Since most of the patients receiving these vaccines are already on death’s doorstep, their depleted immune systems are hard pressed to respond to the treatments. As a result, the trials are unlikely to yield the statistically favorable results preferred by the FDA.

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