Dendreon (DNDN), Provenge and the FDA

The surprise decision by the FDA to ask for more data on Provenge, and essentially keep the drug off the market for another two (to four and one-half) years, has opened a debate on the role of the FDA and how it makes decisions.

Poorly, is the simple answer. The agency is using 19th-century scientific logic to manage the process of approving or rejecting 21st-century drugs.

Strangely, though, the real fault of the FDA lies in not adhering to a standard created in the fourth century BC. It is known as the Hippocratic Oath, the pledge made by physicians on how to best care for their patients. For the full oath, check out Wikipedia's definition. For the purpose of our discussion, the key words are "Do No Harm."

Do no harm is what the FDA forgot - and the four hypocrites on the Advisory Panel who voted against the drug also forgot. Do no harm.

For the vast majority, I would say 99%, of drugs, the FDA standard of "prove you are right, prove you work" is the right way to go with the statistical measure they use, which typically require a company to prove with 95% certainty positive outcomes in a trial are the results of a drug in question. But for drugs such as Provenge, wrong standard, and retreating into this standard not only violates "do no harm" it is an overt act of cruelty born out of cowardice.

Strong words - and I am not dying of prostate cancer.

Why is Provenge different? Because there is no treatment for the form of prostate cancer targeted by Provenge and affecting, conservatively, 45,000-55,000 each year in the United States. By having a patient take Provenge, you are diverting them from another treatment - you are not doing harm.

Yes, there is a chemotherapy called Taxotere approved for treatment, but no one sees this as a real treatment as, on average, it extends life 10 weeks and is terribly harsh, with many, perhaps a majority of eligible patients refusing treatment due to side affects.

But, the FDA says Provenge does not work.

Provenge, to many of us, does work - it is just the size of the clinical trial and the structure of the data collected and submitted to the FDA that did not meet original promises for the trial. And to keep statistics pure, possibly 22,000-plus men will die earlier than they should in the next four and a half years. That is the time I estimate it will take to complete a new trial, present data and get Provenge past the FDA.

I called them cruel, becasue, of course, cruelty does not have to be purposeful -- it only has to mean hiding from what needs to be done. To "do no harm" they are cruelly condemning potentially tens of thousands of men to a premature death. I called them cowards - and let us look at the definition of coward I found:

* lacking courage; ignobly timid and faint-hearted; "cowardly dogs, ye will not aid me then"- I remember that one from Shelley
* lacking determination or strength of character

That sums it up.

Can this be fixed? Not for Provenge - the FDA was designed to be an independent agency, as it should be, and neither the Executive Branch nor Congress can intervene - only the courts and they are justifiably reluctant to do so.

But, can this be fixed. Yes, and simply, without passing new enabling legislation, although the people who run the FDA will probably want a Congressional go-ahead for any sort of meaningful change.

What should that change be? To formally create a new kind of "conditional approval" approval suitable only for severe or terminal illnesses that otherwise have no other viable, alternative treatment. They would be approvals that require a large follow-on trial or epidemiological study of patients using the particular drug. The approval would have a sunset clause - it would be rescinded automatically on a certain date if the follow-on data was not submitted to the FDA in the specified time period and/or if the FDA found the data did not support a full approval.

Is this an overreaction? Even the most conservative estimates place the number of premature deaths due to the denial of approval to Provenge at 22,500 or seven times the current body count in Iraq. Enough said.