As the world knows, the FDA approved Biogen’s anti-amyloid antibody today, surely the first marketed drug whose Phase III trial was stopped for futility. I think this is one of the worst FDA decisions I have ever seen, because – like the advisory committee that reviewed the application, and like the FDA’s own statisticians – I don’t believe that Biogen really demonstrated efficacy. No problem apparently. The agency seems to have approved it based on its demonstrated ability to clear beta-amyloid, and is asking Biogen to run a confirmatory trial to show efficacy.
They will be absolutely overjoyed to do that, of course, because the whole time that’s going, they will be selling the first drug that (in theory) targets the etiology of Alzheimer’s. The backed-up demand is going to be gigantic, and Biogen is going to make enormous amounts of money. They have nine years, as it turns out, to get this trial done, and I feel safe in predicting that it’s going to take alllll niiiiine loooong sloooow years to get this done. Why shouldn’t it? The company certainly showed no interest whatsoever, not even a twitch, in running a confirmatory trial before this, so why should they hop to running one while the drug is selling? I continue to think that odds are quite good, and certainly unacceptably so for Biogen, that the drug will turn out in the end to have no real effect on Alzheimer’s patients at all. I’ve been dreading a decision like this for a long time.
So the FDA has, for expediency’s sake, bought into the amyloid hypothesis although every single attempt to translate that into a beneficial clinical effect has failed. I really, really don’t like the precedent that this sets: what doesn’t get approved, now? I suppose only things that definitely cause harm, because otherwise why not just ask for the same deal that Biogen got, and go out and prove efficacy while you turn a profit? I know that this is just the libertarian turn that many people have wished for, but I’m still not sanguine about it. I’m going to quote myself, because my opinion hasn’t changed a bit:
What would be so bad about moving to an “efficacy not required” regulatory regime? I think that it’s a flight from scientific evidence, which is the only thing we’ve got. Otherwise, everything starts to look like the “dietary supplement” industry, and what a mess that is. Here, you drop the efficacy requirement and I’ll develop grape juice for Dread Disease X. Not just plain grape juice – grape juice concentrate capsules. Mechanism? It’s the bioflavanoids. Probably. I think that they’re antioxidants, among other things. Lots of things. I can show safety in the clinic, too, so you have to approve my grape juice gel caps: I have a mechanism by which they might work (you can’t prove I’m wrong, can you?), I can show they’re safe, and you’ve eliminated the requirement that I prove that they actually do anything useful. Off to market! The patients who unfortunately suffer from Dread Disease X will, I’m sure, pay a lot for something that might help them. Don’t they have a right to try my antioxidants? There’s nothing else like them on the market, you know.
Go ahead and laugh – I mean, yeah, I’m pretty amusing, but I don’t keep grinning as long as I might when this topic comes up. The aducanumab approval, to me, is just a tiny step off of the radio-ad “Not intended to treat, cure, or modify any disease” memory supplements. It’s true that those ads always have to work in the line about how “These statements have not been evaluated by the FDA“, and at least Biogen doesn’t have to say that. Their statements have indeed been evaluated by the FDA, and the FDA has decided to punt on all the important ones and just let Alzheimer’s patients, their families, their insurance companies, and the taxpayers (through Medicare and the VA) pay for it all while we figure it out somewhere around the year 2030 or so.
Here’s Matthew Herper at Stat, talking about that exact FDA rule-change problem, and here’s Damian Garde and Adam Feuerstein trying (perhaps in vain) to estimate just how much money Biogen could be reaping from all this. That’s partly because, as Andrew Joseph notes, the agency applied no restriction at all to what patients can get the drug. Steve Usdin is gloomy about this at BioCentury, and wonders if this is going to open the door to many more such approvals in neuroscience and beyond. Zach Brennan’s not happy at Endpoints, either, and neither is their Bioregnum column. In general, the more you know about drug development and drug approvals, the more likely it seems that this decision came as an unwelcome surprise. That probably goes for plenty of people inside the FDA, come to think of it.
This was disgraceful decision, and we’re all going to be dealing with the consequences of it for years to come.