You can get either answer, depending on whom you ask. Last month, the agency unveiled new guidelines for developing Alzheimer's therapies. They're trying to deal with the difficulty of showing actual cognitive improvement in more advanced patients, while at the same time figuring out how to evaluate therapies in early-stage patients who really aren't cognitively impaired yet. It's a worthy problem, for sure, and a good thing to be thinking about. Two of the agency's scientists laid out the thinking in a NEJM editorial:
The current landscape of research and drug development in Alzheimer's disease offers a study in contrasts. On the positive side, numerous discoveries over the past decade have begun to unmask complex pathophysiological processes that underlie disease progression. Such advances have, in part, resulted from large, well-organized observational studies, such as the Alzheimer's Disease Neuroimaging Initiative (ADNI), that have elucidated various disease biomarkers that reflect, or even predict, the progression of disease. On the negative side, drug discovery has been disappointing. Despite all best efforts to translate mechanistic insights concerning Alzheimer's disease into new drug products, several candidate agents have failed to demonstrate efficacy in large, well-designed, phase 3 clinical trials of late-stage disease.
That they have, and how. Avoiding these, or at least finding out ways to fail more cheaply, is very much on the minds of everyone working in the field. The New York Times, though, had a rather unexpected fit about the whole idea, culminating in this editorial:
. . .The goal is commendable — to find ways to prevent or slow the progression of this terrible disease before it can rob people of their mental capacities. But the proposal raises troubling questions as to whether the agency would end up approving drugs that provide little or no clinical benefit yet cause harmful side effects in people who take the medications for extended periods. . .
. . .F.D.A. officials say they would never approve drugs based on cognitive effects alone unless absolutely convinced that patients with very early-stage Alzheimer’s that is likely to progress to full-blown dementia could be reliably identified. It will be up to the drug companies or other sponsors of clinical trials to do the convincing.
The F.D.A.’s proposal is open for comment for 60 days. Independent analysts need to look hard at whether the F.D.A. should lower the bar for these drugs — or should demand a very high level of proof of safety and effectiveness before exposing still-healthy people to possible harm. Even if drugs are eventually approved under this new approach, it will be imperative to force manufacturers to conduct follow-up studies, as required by law, to see if patients benefit in the long run. . .
That's not a crazy point of view at all, though - I've worried about something similar myself. But I think that the Times is a bit too worked up over the current FDA guidance. On the other hand, as BioCentury has it in their latest issue (March 25), there are people in the biotech industry who have been talking up the new guidelines as some sort of regulatory breakthrough. "Not So Fast", is the response:
. . .The only reasonable conclusion to be drawn from a careful reading of both the guidance and the commentary is that while FDA would be willing to accelerate approval of AD drugs, the science isn’t there to allow it to do so. . .
The guidance states FDA would grant accelerated approval to a treatment for AD “based on the use of a biomarker as a single primary surrogate efficacy measure” — if a biomarker that reliably predicted clinical benefit existed.
As the guidance notes — and as anyone who follows the field knows — “no reliable evidence exists at the present time that any observed treatment effect on such a measure is reasonably likely to predict ultimate clinical benefit (the standard for accelerated approval), despite a great deal of research interest in understanding the role of biomarkers in AD.”
. . .The process of reaching scientific consensus on an appropriate assessment tool will take years. And no one knows how much longer it will take for regulators to generate sufficient confidence in the tool to use it as the sole basis for approving an AD drug.
I think that's the key part of all this. It's fine that the FDA is open to the idea of biomarkers for Alzheimer's; we're probably going to have to do it that way. But no one knows how to do that yet, and it's not like the agency is just going to pick one of the current measures and tell everyone that that's fine. What I would expect this latest initiative to do, actually, is to end up pushing more money into the hunt for such biomarkers, with perhaps less going to direct shots-on-goal. That's disappointing, from one perspective, but the shots on goal will bankrupt us all at the current rate.