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I’ve been traveling and haven’t had time to comment on the latest news on Biogen’s (BIIB) Aduhelm, the controversial anti-amyloid therapy for Alzheimer’s. The Medicare CMS issued its final decision that they are indeed only going to pay for the drug in the context of a clinical trial. This is what they had proposed back in January, and this decision has set off the same objections that it did then. Over at Stat, they published opposing editorials from outside contributors: a positive view on the decision from two Alzheimer’s physicians at UCLA, and a negative one from two longtime advocates of anti-amyloid therapies. Those two will lay out the issues as well as anything.
That first link above will lay out mine, as well, but Steve Usdin does a great job here at BioCentury (free to read), and my thoughts parallel his. He makes an underappreciated point, that one of the underlying causes of this debacle is a lack of clarity at the FDA about the surrogate markers used for the whole idea of accelerated approval in the first place:
In Aduhelm’s case, FDA said in a 2018 draft guidance that “the effects on biomarkers in AD are not sufficiently well understood to provide evidence of a persistent effect on disease course,” and it told the Aduhelm advisory committee that accelerated approval wasn’t being considered.
The controversy raised by the FDA’s decision to disregard its advisory committee’s recommendation against approving Aduhelm, and CMS’s highly restrictive coverage decision, based on a repudiation of basing approvals on reductions in β-amyloid deposits, illustrate the negative consequences of failing to achieve consensus about or at least publicly justify the use of, a surrogate endpoint.
I think that CMS made the right call and that it’s unfortunate that it had to come to this because the FDA started off by making the wrong one. And that’s why I object the most to the way that PhRMA and the Alzheimer’s Association have framed their objections. They’re going with “how could Medicare do this to needy patients”, and “this means accelerated approval is a cruel hoax”. Maybe not quite in those words, but that’s the message, and I strongly disagree. PhRMA, for example, is saying that CMS is “undermining the scientific assessment by experts at FDA“. That’s a particularly slimy way of putting it, since the FDA’s own statisticians strongly objected to the idea of approving Aduhelm at all, and several members of the agency’s advisory committee resigned after their solid “No” vote was ignored. Framing this as the FDA versus Medicare is disingenuous – this was the FDA versus the FDA to start with, and don’t pretend otherwise. To me, accelerated approval still means that you still have to show that your drug does something and that its benefits outweigh its risks. It does not mean that your drug gets approved anyway even if it doesn’t have compelling evidence that it works, all the name of accelerating things. Let’s not confuse it with some sort of “accelerated revenues” program.
Everyone knew the score already or should have: you have to show efficacy. The FDA are the ones who have taken some really unfortunate decisions that loosen that (with things like the Sarepta (SRPT) decision and this Aduhelm one), and one of the unfortunate things about these is that many people will take (and have taken) them as establishing some sort of “new normal”. What’s more, for fear of setting off more objections the people objecting will pretend that we have the same regulatory environment we’ve always had and that things like the latest CMS decision is some terrible and unwarranted tightening of the rules. But that’s spin, not reality.
Attempts to argue that this will have some sort of chilling effect on Alzheimer’s research and other areas fall flat with me, too. For example, Dennis Selkoe and Jeffrey Cummings, in their Stat editorial, finish up by saying “CMS’s decision will affect the exploration for new treatments for Alzheimer’s for years, just at the time when new drugs appear to be making progress against this terrible disease.” Neither half of that sentence is true, as far as I’m concerned. For the first part, consider how long it takes to get a proposed Alzheimer’s therapy to and through the clinic: there’s a lag time of many years. Anything that’s working its way through the clinic now has been doing so under the assumption that its developers would have to show some sort of meaningful efficacy, and the CMS decision just reaffirms that. And meanwhile, if there are any preclinical programs that were about to launch based on the “Well, we only have to do as well as Aduhelm” theory (a risky move indeed), we weren’t going to see those before the FDA until some time past 2030, if ever.
So as it stands, Biogen is about to enroll patients for its trial, and I hope that I’m wrong when I think that this is taking place sooner than it would have if Aduhelm had had a successful launch into the market. And there’s speculation that the company (perhaps joined by others) might sue Medicare over the CMS decision on the grounds that the agency overstepped its authority. That has the potential to screw things up tremendously, but I’m going to wait to have a fit about that until it actually happens, since it may well not. My question is, who is it that has the standing to sue the FDA for approving Aduhelm in the first place?
Disclosure: None
Editor’s Note: The summary bullets for this article were chosen by Seeking Alpha editors.
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