The Future of Alzheimer’s Pharmaceutical Aducanumab – as a Medicine and as a Financial Product – What Happens Now?

Yves here. This post from Health Care Renewal continues with its discussion of aducanumab, a drug so unlikely to make a material difference to Alzheimer’s victims that absent the mind-blowing price tag (estimated at $56,000 a year), it looks like Big Pharma’s answer to faith healing. It discusses what outcomes are probable, including the grotesque enrichment of its creator, Biogen, at the expense of patients and insurance programs, including Medicare.

In other words, if you think aducanumab isn’t your problem, think twice. Medical-industrial complex grifting is the big reason the US has vastly higher healthcare costs, in percentage of GDP terms, than any other economy, yet has middle of the road to lagging results compared to other advanced economies. Compared to other plays, like private equity employed outsourced hospital staff acting as a vehicle for rent extraction via “surprise billing,” the aducanumab fleece is very easy to understand.

Public Citizen has been on the case and is having an impact. From an e-mail yesterday. Notice a key point, that that $56,000 annual drug price tag doesn’t capture the total costs:

We demanded that the FDA revoke its approval because there is nowhere near enough evidence that aducanumab is effective.

This morning — following intense pressure from Public Citizen and allies — the FDA narrowed its prescribing recommendations for this unproven medication.

But we still think the FDA should revoke its approval of aducanumab altogether. Because:

• Geriatric experts and the FDA’s own independent advisory committee strongly urged the agency NOT to approve the medication.

• Public Citizen even called for an investigation of the inappropriately close collaboration between the FDA and Biogen — the pharmaceutical company that developed aducanumab — in analyzing clinical trial data.

• Beyond insufficient evidence of effectiveness, aducanumab has potentially serious side effects. For example, 40% of people who took it in clinical trials had swelling and bleeding in their brains.

• What’s more, Biogen is planning to charge an average of $56,000 per patient per year for the treatment. (And that doesn’t even include potentially tens of thousands more per patient in screening and monitoring costs.)

• That price tag is so exorbitant that it might single-handedly jack up insurance premiums across the board and drain tens of billions a year from Medicare.

Please consider donating to Public Citizen. They take no prisoners.

Even though the FDA concessions signal the agency recognizes it is exposed, the only proper remedy is revoking the aducanumab approval. An MD can prescribe a drug for any “off label” use, so the FDA tightening its prescription recommendations means little in practice.

By APeticola. Originally published at Health Care Renewal

To recap: the FDA recently (and foolishly) approved Biogen’s monoclonal antibody aducanumab as a treatment for Alzheimer’s. It did this on the basis of a surrogate endpoint, amyloid plaque reduction, even though, in NUMEROUS trials, that has not been associated with clinical improvement. The company is claiming that there IS clinical improvement based on high-dose patients in one of two clinical trials that were stopped for futility, based on a post hocanalysis. According to an NEJM Viewpoint article authored by three of the FDA advisory committee members, those patients had an absolute improvement of 0.39 on a clinical scale (the Clinical Dementia Rating-Sum of Boxes) but “the minimum clinically important difference [on this scale from 0 to 18] is generally considered to be 1 to 2.” The FDA advisory committee was overwhelmingly unconvinced this showed the drug to be effective, but the FDA went the “accelerated approval” route and approved it anyhow, on the basis that it shrinks amyloid plaque.

Rescission of Approval – Best Case Future, but Unlikely

Best case for what happens now is that approval is rescinded, and I think that we SHOULD absolutely push for that sliver of a chance that that could happen. The volume of informed voices protesting the accelerated approval is somewhat heartening, and might indicate wide support for such a move. All the same, that’s a very remote possibility, with FDA leadership firmly opposed, even though a couple of congressional committees are supposed to be looking into the approval. So if rescission doesn’t happen (and I’d have to say it won’t), what now?

The Future According to Proponents

If one listens to the proponents of the drug, what happens next is likely to be a golden era of progress in treatment for Alzheimer’s. Yes, maybe Aduhelm isn’t very effective overall, but it’s a start and may help some people much more than the average outcome indicates. As a start, it will be followed by better drugs and is the beginning of a new era. The high price is warranted because Alzheimer’s is a huge problem, so even marginal help is of immense value, especially if it accelerates greater progress as more drugmakers jump on the bandwagon.

A More Realistic Rosy Scenario

I think some people, including acting FDA head Janet Woodcock, have convinced themselves of the above golden future, but I believe this is a ridiculous fairy tale and about as likely as snow in July. So here’s my version of a rosy scenario: insurers and legislators force down the price of Aduhelm somewhat, and it’s prescribed to a large number of people but not as large as originally predicted. The brain swelling side effects prove to be not too troubling, and although clinical effects overall are marginal to none, it does help some people more than averages would indicate, and some individuals do realize a substantial benefit for themselves.

Even in this most rosy of realistic scenarios, the financial impact of the drug will be major, causing huge financial stress on both individuals with Alzheimer’s and on the medical/insurance systems. As well, research on more promising avenues to treat Alzheimer’s will likely be impeded, both because it will be more difficult and complicated to enroll people in clinical trials, and because if companies are incented to develop lousy drugs and can make a fortune that way, the incentive to produce really great drugs is thereby diminished. And, as Elizabeth Rosenthal pointed out in an excellent and interesting column, after the accelerated approval, we may in fact never learn whether Aduhelm actually works or not.

The most Likely Future

A less rosy but perhaps more probable scenario – the one I personally would wager on though I could be wrong – is that the drug will be approved, be widely prescribed, and provide no discernible or provable benefit to anyone, while worsening the lives of patients financially and by additional medical procedures and tests and side effects. Desperate people will be provided with false hopes and real costs.

I think this is most likely, because there is not something like an even chance that aducanumab is effective. Given the dicey nature of post hoc analyses and the many failures of amyloid-targeting drugs, the smart bet is that this drug doesn’t work, although that’s not a certainty.

Aducanumab and Money

The future of aducanumab as a medical product is murky and uncertain, but the future of aducanumab as a financial product is something else. It looks to extract vast amounts of money from people in the form of premiums, taxes, and co-pays, and to greatly enrich Biogen and its stockholders.

Vinay Prasad had comments on drugs that are primarily financial products on a recent podcast (at 18.05 minutes in, but to get the full context, start listening at 15.51). He was not specifically addressing aducanumab, which had not been approved at that time, but thinking more of some cancer drugs. Prasad noted:

[When the FDA approves drugs without good evidence,] they keep so many people happy in the ecosystem, the companies are happy, the providers are happy, the people running the trials are happy, the patient advocacy groups, who are funded by the companies, they’re happy, but the people who aren’t happy are, the average person in society, whose premiums are going up, whose real wages are stagnating or declining. because we’re paying more in health care, and this person is seeing more and more of their paycheck going off to health care, and what is that really saying?

it’s saying that we’re going to take this money from you, and we’re going to collect it from everybody, and offer a service to everybody that we believe is a human right, the right to have good health care, and I actually support that, I believe that is a human right, but it’s a human right to have things that actually benefit you – is it a human right to have snake oils or things that don’t work? That I think is actually a financial product.

I mean, if I make a molecule, that is patentable, and I give it to cancer patients in a trial and I find some changing biomarker, and I give it to people in the real world, not a single one of them or nobody in aggregate lives a day longer and their quality of life is the same, what have I created? It’s something that you call a medicine, you call it a medicine, but people aren’t living longer, they’re not living better, with my medicine, hypothetically – it’s not a medicine, it’s a financial product.

It’s a product that actually collects wealth from lots of people, from middle-class people, from poor people, and it shovels that wealth into the hands of a few shareholders of this company, it is a reverse financial product, it’s like a regressive financial product. …there have long been feudal systems, where average workers kick up some of their wealth to the elites, and to some degree, when you have cancer drugs that don’t work, you have created a feudal system, we’re all kicking up our wealth, so that some people get really rich, and whether or not we get better health for it, is an uncertainty. and I think that’s the crux of the issue.

We do not know if aducanumab is a medicine in any true sense of the word at all. We are pretty certain that it’s a good business proposition and a money-maker, even if it might be snake oil. And we know that, like so many things nowadays, it will suction money upwards from the less well-off to the richer, and contribute to inequality.

And how MUCH money will it suction away from other uses? That too is an interesting question, although one with no certain answer other than “a lot,” and perhaps the one that has caused the most speculation and discussion to date. I’ll post more on the finances and perhaps some other aspects later.