Biogen (and a lot of other people) have been waiting to see what Medicare makes of their FDA-approved antibody therapy for Alzheimer’s, Aduhalem (aducanumab). Medicare is going to be a big driver of the spending on any Alzheimer’s drug, naturally, and normally an FDA approval would make Medicare’s approval for payment almost automatic. Not this time. I won’t recapitulate the entire story, but the approval of Aduhelm has been. . .controversial. And the launch of the drug has been a mess as well, with many insurance companies and hospitals saying that they won’t pay for it. So the Medicare decision is an even bigger deal than ever, because many organizations are going to take their own cue from it.
Yesterday the Centers for Medicare and Medicaid Services (CMS) finally announced their decision: they will not pay for Aduhelm outside of its use in a controlled clinical trial. I think that’s an excellent call, and I can recommend the full CMS document as a summary of the state of Alzheimer’s research and therapy. It goes into the reasons to believe that amyloid is an appropriate target for treating the disease, and it goes into the reasons to doubt that idea. “The role of A-beta as cause versus marker of disease remains controversial“, it concludes, and boy does it ever. It also notes that the therapeutic landscape is barren, and that existing medications “do not prevent, halt, or slow – let alone reverse – the disease“. That’s the hard truth, too, and they get to another one when reviewing anti-amyloid antibodies in general: “To date, no trial of an antiamyloid mAb has confidently demonstrated a clinically meaningful improvement in health outcomes (i.e., cognition and function) for AD patients. Thus, there is insufficient evidence to conclude that the use of monoclonal antibodies directed against amyloid is reasonable and necessary for the treatment of Alzheimer’s disease. . .” What’s more, given the side effects seen in the clinical trials of such agents, CMS concludes that evidence so far does not support the idea that the benefits – if any – outweigh the harms involved.
And as for Biogen’s own arguments that their trial data showed a benefit to patients, the document says:
“Many published expert opinions and reports have questioned Biogen’s secondary analysis of trial data and its conclusions regarding aducanumab’s effectiveness. Most experts believed there was little, if any, reliable evidence to answer the key question of clinical benefit.. . .Our conclusion is that Biogen’s secondary analysis cannot overturn, definitively confirm, or substitute for, the RCT evidence. With conflicting results from two RCTs (EMERGE and ENGAGE), and a secondary analysis that did not resolve the difference between the two RCTs, CMS believes that the available evidence is insufficient to establish that the treatment is reasonable and necessary. . .“
I could not agree more. The CMS document goes on to spell out exactly the sort of clinical evidence that it believes is necessary for full reimbursement, and exactly the sort of clinical trial that it will approve the use of Aduhelm for in order to generate such data. But they’re not approving payment for it for anything else. All this simply makes the FDA’s approval decision more inexplicable, and (and many have pointed out) it opens the biggest gap that I think we have ever seen between a Medicare recommendation and the FDA. I’ve said many times that I think the Aduhelm approval was one of the biggest mistakes I’ve ever seen the agency make, and this is more evidence for that position.
Biogen, of course, is out with statements about how this will restrict so many Alzheimer’s patients from getting this FDA-approved drug, how can you do this to people in need, and so on. That same link has a statement from the industry trade group PhRMA: “With this proposal, CMS is writing off an entire class of medicines before multiple products have even been reviewed by FDA, positioning itself and not FDA as the key arbiter of clinical evidence.” And that is some crap, let me tell you. You know what’s been writing off this entire class of medicines? Their clinical trial results, which have been relentlessly negative. Believe me, if one of the other anti-amyloid antibodies shows up at the FDA with (for once) actual positive evidence of benefit and a favorable risk analysis, I’m sure CMS will cover that gladly. This is a decision about Aduhelm, based on its own clinical data and the class data that have been generated so far. Got something better? Roll it out and let’s have a look. No, that PhRMA statement is shameful obfuscation and it’s even more evidence of the harm that the Aduhelm approval is doing. PhRMA should want drugs that work; instead, they’re coming out in favor of drugs that are approved and are reimbursed by insurance, and Aduhelm is evidence that those categories are not the same. I wish they were. I wish a lot of things.
