In the wake of the FDA decision earlier this month to issue an approvable letter to Dendreon with respect to their anti-prostate cancer prototype treatment, Provenge, there has been a lot of speculation that some combination of hedge funds who had massive short positions and big pharma companies who market chemotherapy products somehow improperly influenced the decision.
The FDA decision to go against the advice of their own advisory committe—who voted 17-0 that Provenge is safe and 13-4 that is is probably efficatious—was a most definitely a shock. And it does appear that two of the panel members who voted negatively on efficacy had serious conflicts of interest, and certainly those two individuals later wrote letters to the FDA criticizing the majority recommendation. However, I think if the takeaway here is that the system worked well, and it was only some dark grassy knoll conspiracy that subverted what would have been the right decision at the last minute, then I think we are making a big mistake.
IMO, anyone who seriously believes the FDA careerists give a hoot about hedge fund shorts is a candidate for a flying saucer ride. And anyone who asserts that they are accepting bribes from big pharma to defend chemo franchises is not much better off…perhaps a candidate for a black helicopter ride.
No, what happened here is that the system worked exactly the way it was designed to work…except for the AC meeting efficacy vote, which due to what in retrospect was clearly an anomalous alteration of the question in the middle of the vote, came out unexpectedly in favor of Provenge. The FDA approvals process is designed to weed out any product that does not meet stringent standards. The folks who man the bulwarks there live to find “exceptions” to the straight and narrow, and stamp REJECT and RETURN TO SENDER in red ink all over them.
Such a process does not cope well with innovative products, and the handling of Provenge has consistently reflected that weakness: picking the wrong endpoints for the first two studies, screwing up enrollment of the second study, giving Dendreon management false encouragement about the outcome of the BLA, the changed question fiasco at the AC, just to name a few examples.
But this case is different, we thought. FDA Chairman Dr. von E wants to build a bridge, we thought. The FDA need immuno therapies in general—and Provenge in particular—to beat cancer by 2015, we thought. The pleas of the individual patients and providers at the AC—the very same ones that dissenter Dr. Hussain slept through—were so compelling, we thought.
LOL what we forgot about in our zeal and excitement to be part of a potentially major achievement for humanity was the old story about the scorpion and the frog…you know, the scorpion needs to cross the river and pleads with the frog to carry him but the frog refuses, explaining, “If I let you on my back, you will just sting me!” To which the scorpion replies, “Don’t be ridiculous, it makes no sense for me to sting you…I can’t swim…I can’t get across the river on my own…besides, not only do I need you to cross the river, but if I were to sting you while we were doing it, you would be paralyzed and sink…and I would drown!” So the frog relents and they get halfway across…and the scorpion stings the frog! As the poison flows through her body and the frog begins to sink beneath the surface, she croaks out, “Why did you do it? Now we will both drown!” Replies the scorpion, “I know…I’m sorry…but I can’t help it; it’s my nature.“
I accept that this decision is likely—given that Provenge probably works—to result in unnecessary pain, suffering, and death, to sink Dendreon, and to minimally push back the development of immuno therapies for cancer if not all manner of innovative medical products…that damage is now water under Dr. Von E’s mythical bridge.
But going forward, we have a problem: the FDA are so inflexibly inept at dealing with innovative products that they have created conditions where shortsellers are shooting biotech applicants like fish in a barrel. This “surcharge” on investors hurts not just Dendreon, not just immuno therapy research, not just innovative medical research in the USA in general, but humanity as a whole, to the extent that such research might advance the ball to our mutual benefit.
Now I am not saying this is black and white.
I appreciate the power of biostatistician Thomas Fleming’s implicit argument that the damage to the process of approving a red-stamped product outweighs the benefits of likely being correct in this particular case…because it would compromise the agency’s capacity to say “NO” in the 99% of such cases where that is the right answer. Mr. Fleming knows his stuff, and he is fighting his own personal battle with prostate cancer, so clearly he does not reach this conclusion lightly.
I appreciate that the FDA should not heavily weigh anecdotal testimony in making approval decisions (albeit sleeping through patient testimony is bad form).
I appreciate that in general, we want unimaginative martinets at the FDA to protect us from snake oil.
But to me, it appears that the FDA are floundering around in the middle of the river with no idea how to swim when it comes to Provenge.
To me, the right takeaway here is that we need to seriously consider whether as presently constituted their inability to make an exception to their “no exceptions” policy does us more harm than good.
To me, that has to be the focus here.
If we divert our energy chasing black helicopters and digging up the grassy knoll looking for shell casings and corruption, we will, in effect, be throwing good energy after bad money…and it won’t help the frogs in the least.