Money and Aducanumab

In my previous posts, I haven't talked too much about the price set for aducanumab. Since I think it should not have been approved on current evidence regardless of price, the approval has been my focus. But of course the price is an issue, especially given that there is a HUGE pool of potential patients and that most are probably Medicare age, meaning that this drug can have huge impacts on Medicare costs.

Before and after approval, there was speculation that this "potentially zillion-dollar moneymaker" (as Sharon Begley called it in October 2019) might be the most lucrative drug ever. Last November it was noted that if it brought in even a fraction of potential patients, it could still realistically be a $60 billion/year drug, changing Biogen's revenue picture dramatically.

Taking a high-side estimate of $110 billion/year, Nicholas Bagley and Rachel Sachs speculated in The Atlantic that Aduhelm could be the drug that breaks Medicare, given that that cost exceeds total current Part D medication expenses of $90 billion dollars.

Even at a much lower total, Aduhelm's costs would still balloon Medicare costs and would exceed the total NASA budget of $23 billion. Regardless of the exact total, the hit to Medicare would be big.

The cost to Medicare...could be substantial.... In 2017, nearly 2 million Medicare beneficiaries used one or more of the currently-available Alzheimer’s treatments covered under Part D, based on an analysis by the Kaiser Family Foundation. If one-quarter of those beneficiaries are prescribed Aduhelm, or 500,000 beneficiaries, total spending for Aduhelm in one year would be nearly $29 billion. This assumes Medicare will pay 103% of the list price until an average sales price is established. In any event, the Kaiser estimate suggests the total cost would far exceed spending on any other drug covered under Medicare Part B or Part D, based on 2019 spending data. “To put this $29 billion amount in context, total Medicare spending for all Part B drugs was $37 billion in 2019,” Kaiser wrote.

We get to these high numbers because the company set the cost at $56,000/year. $56,000 is a very high price for a drug no one thinks has more than a moderate and subtle clinical benefit. I was struck by this reflection:

“I cannot think of a justification for that price for this drug given the evidence thus far except that Medicare will pay it,” said Walid Gellad, an associate professor of medicine who heads the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. “If $56,000 is a reasonable price for this drug, then what [would be] a reasonable price for a drug that has a large impact on changing the course of Alzheimer’s?"

That's an excellent question. Another meaningful question is whether anyone will put in the effort to develop really good drugs for Alzheimer's, if you can make this kind of money from a drug that is at best marginally beneficial and possibly not beneficial at all.

Because, for all this money, how meaningful are the benefits? In short:

“Absolutely tiny,” said UCL’s Howard. Aducanumab “didn’t stop dementia or reverse it, and even if we take the data at face value, the benefits are practically undetectable. As a clinician, it would be nearly impossible to tell if it works in one of your patients.”

Nonetheless, the Biogen CEO said he wasn't worried about blowback on the price, comparing the price to that charged for other monoclonal antibody treatments like Humira and Keytruda.

Even some who are enthusiasts, like the Alzheimer's Association, have questioned the high price of the drug, although there is some question about whether some of that is performative. This doubt partly arises because

months ago, the association also gave Biogen some cover for setting a higher price for its drug. It repeatedly sparred, for example, with the drug pricing watchdog ICER after the group suggested Aduhelm was only worth between $2,500 and $8,300 per year. (Meyer, the group’s spokesman, pushed back against the idea that its criticism of ICER had made it easier for Biogen set a higher price, calling the idea “patently false.”)

One thing that has not been much noted is that the price for many individuals will be HIGHER than $56,000/year, because the drug is dosed by weight, and $56,000 is the price per maintenance dose year for an "average weight" of 74 kg (about 163 pounds), so many will have higher costs (and higher co-pays).

Although it won't likely change the total financial impact, Biogen's share of the market may be reduced quickly, because after aducanumab's accelerated approval, other companies, including Eli Lilly and perhaps Roche, are hoping to speed up approval of other such drugs. Biogen too with its partner Eisai has another amyloid-clearing drug in the works.

There's more to say about spending so much money for so little benefit and I may or may not get around to another post on that topic. But meanwhile, I have been a bit gratified - and Biogen has been very put out - to see that there has been major pushback from multiple players on the accelerated drug approval and on the cost. Insurers and major hospital systems alike are reluctant to get the ball rolling on this. It's probably just a slowdown, but Biogen is whining a lot. In an open letter, Alfred Sandrock, their Research and Development head, wrote:

Unfortunately, ADUHELM’s approval has been the subject of extensive misinformation and misunderstanding. It is normal for scientists and clinicians to discuss data from experiments and clinical trials, to debate, and to disagree, on the interpretation of data. That is how science advances and we welcome these discussions. Recently, however, there has been a turn outside the boundaries of legitimate scientific deliberation.... ADUHELM is the first Alzheimer’s treatment approved since 2003. An important question is being overlooked by many: what would be the impact of deferring access to this treatment, despite the clinical data underlying its approval? Based on our current estimates of the progression rates of the disease, every day over 1,000 Americans will advance from early stages of disease to moderate and severe stages of disease, and thus may progress beyond the stages during which ADUHELM should be initiated. We feel a strong obligation to be able to offer new options to patients with this devastating disease.

And when Biogen is not whining, it's rolling out an aggressive marketing campaign to get people to worry about their memory capacities. Its website with a doubt-inducing quiz sends all comers (even if they answer all questions negatively!) to consult with their doctor for cognitive testing to determine if they may have early Alzheimer's and be a candidate to take Biogen's at-most-marginally-effective and expensive drug.

The Future of Aducanumab - as a Medicine and as a Financial Product - What Happens Now?

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 hoc analysis. 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.

Leadership of Big Health Care Corporations Go Back to Financially Supporting the Opponents of Democratic Governance

At one time, leadership of large health corporations were circumspect in their financial support for US politicians and political causes. They provided some funds directly to politicians and poltical organizations, but often amounts given to different parties and organizations with different ideologies were balanced. Presumably, the goal was to promote access to whomever was in power at any given time. 

With the rise of Donald Trump, things changed. Many leaders apparently went all in for Trump and his Republican supporters.  In June, 2018  we discussed how CVS channeled money to a "dark money group," that promoted Trump administration policies, including repeal of the Affordable Care Act (ACA). In October, 2018, we discussed important but incomplete revelations about corporate contributions to such dark money groups that mainly favored again right-wing ideology, the Republican party, and Trump and associates. In November, 2018, we noted that health care corporations funneled funds through dark money organizations to specifically attack designated left-wing, Democratic politicians. In March, 2019, we discussed how in the 21st century, health care corporate CEOs' personal political contributions were increasingly partisan, that is individual CEOs gave predominantly or exclusively to one party, and for the vast majority, to the Republican party. 

 

Some corporations paused some of their political giving after a mob whipped up by Trump at a January 6, 2021, rally violently stormed the US Capitol to try to prevent the certification of the 2020 election. However, within two months they started giving again in support of Republicans in Congress who voted not to certify the election (see this April, 2021, post).

Now two new reports show continuing support by large health care corporations for Republican legislators who also supported the nullification of the election, and legislation that might decrease voting by citizens who oppose Trump

Health Care Corporate Sponsorship of Voter Suppression

In April, 2021, Public Citizen published "The Corporate Sponsorship of Voter Suppression." It detailed support from direct corporate contributions and corporate political action committees (PACs) from 2015 through March, 2021, to state legislators who authored, sponsored or voted for 245 bills that could have made it more difficult for citizens to vote in elections. 

The 25 companies contributing the largest amounts of money to these legislators included UnitedHealth Group ($411,200 total); Pfizer ($308,085); and Centene Corp ($205,200).  Companies that gave somewhat less included Merck ($180,000),  CVS ($174,000), Anthem ($138,150) Eli Lilly ($124,000) and Cigna ($109,225).

Two health care related trade groups also gave significant funds to these legislators: the Virginia Dental Association ($223,000) and the  Pharmaceutical Research and Manufacturers Association of America/PhRMA ($200,000).   

Note that the data did not include personal contributions from corporate leaders, and could not include corporate money directed to dark money organizations that ended up supporting these legislators.

Health Care Corporate Sponsorship of the Attempt to Overturn the 2020 Election

In June, 2021, Citizens for Responsibility and Ethics in Washington (CREW) published "This Sedition is Brought to You By..." It detailed contributions from corporate PACS and trade groups to those in the US Congress who voted against certifying the results of the 2020 election and the two main party organizations that supported them, the National Republican Senatorial Committee (NRSC) and National Republican Congressional Committee (NRCC) since the vote not to certify.  

The largest contributions from health care corporate PACs included those tied to Fresenius Medical Care Holdings ($76,000); CVS ($45,000); Cigna ($42,500); Johnson & Johnson ($30,000); Pfizer ($20,000); and Humana ($15,000).

Note that the data also did not include contributions from corporate leaders, and could not include corporate money directed to dark money organizations that ended up supporting these legislators. 

Discussion

Most health care corporations profess to missions that are pluralistic and support the community and society as a whole.  For example, Pfizer's mission statement includes:

We partner with governments, non-profits, and other organizations to ensure that more people around the world have access to the medicine and resources they require.

UnitedHealthCare's mission statement includes:

UnitedHealthcare is dedicated to helping people live healthier lives and making the health system work better for everyone

Merck's mission statement includes:

We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships

However, leaders of some large health care corporations saw fit to direct contributions to politicians who promoted anti-democratic policies. Funding political leaders who would restrict voting rights in ways likely to impact already disadvantaged groups, and challenge election outcomes without strong evidence of irregularities would seem to violate high-minded corporate pledges of inclusiveness like those above.    

Is it that health care corporate leadership just are more interested in making money than in bettering society, despite their aspirational mission statements? As we previously discussed, that is a plausible formulation.  For example, per the Washington Post in January, 2021,

'Their attitude was: ‘Let’s take the big tax cuts and hold our noses for the obvious xenophobia and authoritarianism.’ It was a classic Faustian bargain,' said Rep. Brendan Boyle (D-Pa.), a member of the House Ways & Means Committee.

However, there are problems with this formulation.  As we wrote before,  it is obvious why a pharmaceutical company might want to defeat legislation that would lower its prices or raise its taxes.  It is not obvious why it would want to consistently support actions by one party, or by people at one end of the political spectrum, even if some such people seem generally "pro-business."  After all, for years big corporations and their executives openly gave money to both US parties and their candidates, apparently in the belief that this would at least allow more visibility for the corporations' priorities no matter who was in power.

Maybe it is not just about money.  Again, as we said before, by virtue of being top management of a corporation, particular individuals can control political funds far beyond what they may be able to control as private persons, and to do so anonymously.  It may be that top corporate leaders are not just interested in making more money.  Some may also be interested in personal political power, or have other ways they might benefit from anti-democratic, if not openly fascist national political leadership.  Big industrialists have backed authoritarian and openly fascist regimes in other countries before, some to make more money, but in retrospect, some for darker reasons. (See, for example, this article on how German industrialists financially bailed out the Nazi party in 1932.)

At least health care professionals, policy makers, patients and the public at large deserve to know how health care corporate leadership is directing money to political causes, and how they benefit from doing so.