We are helping lead a push to demand the FDA withdraw Biogen’s license to market aducanumab. To co-sign the Citizen’s Petition, click here.
Why we must lance the Alzheimer’s boil
Sometimes social pressures come to a head, and a moment of crisis offers opportunity. With the disastrous FDA approval of aducanumab (or Aduhelm, as the drug is known in its commercial existence), the figurative “boil” of the Alzheimer’s disease movement has done just that. Will this swelling reach a point where we can “lance the boil” to relieve the pressure of false expectations and hopes, or will the infection spread and continue its permanent scarring of this wayward movement?
The Alzheimer’s Association and its allies are largely responsible for this approval and its grotesque excesses. At least that is what they implied in their recent Special Volunteer briefing The Association advocated for approving this potentially dangerous drug (biologic) and supported an FDA commissioner who has favored industry in other decisions. Most relatively unbiased experts (FDA statisticians, FDA panelists, and many, if not most, outside experts) said the science was not adequate to warrant approval and recommended further well-controlled studies. A few of the highest paid, most visible, and most coopted experts supported the decision—no surprise there. The Accelerated Approval mechanism, not presented in advance to the FDA expert advisory panel that voted nearly unanimously against approval, was based on biomarkers that have not been adequately validated. No trials of amyloid agents have clearly linked cognitive improvement to this biomarker or any other, at least in the view of most experts.
So who benefits from this scenario? Clearly Biogen, whose financial fate was highly dependent on the outcome and chose to immediately announce a price ($56,000) far beyond what experts felt was fair. The company then stated it would not proceed with urgency on further studies required by the FDA as part of the approval. The FDA gave Biogen nine years to report and, critically, did not specify what kind of follow-up study would be required. More placebo controlled randomized trials would be optimal, but that should have been required before a decision was made. (How do you randomize potential participants to placebo arms when there is an “approved” product?)
The full implications of what we stand to lose due to FDA approval have not yet been laid out, but the financial cost to taxpayers will be enormous (indeed, the Times reported last month that projected costs of aducanumab—which, along with related care could cost over $100 billion a year—will well exceed the budget of NASA and the CDC), as will lost funding opportunities for public health measures that will improve brain health. Let’s hope payers and policymakers offer more reasonable voices that put a damper on the Biogen money machine. However, already, other drug companies like Lilly and others are quickly leveraging the aducanumab decision to seek accelerated FDA approval for their own biologics, which have similarly not proven effective. The FDA lowered the bar so far that a whole procession of me-too drugs can practically stumble over this pathetic regulatory hurdle.
Perhaps the biggest beneficiary of the approval is the Alzheimer’s Association. But it must be asked whether this advocacy organization has won a battle but perhaps lost the war with this Pyrrhic victory. The Alzheimer’s Association is the dominant purveyor of the scientism and economism of the field—as expressed in organizational advocacy phrases like, “Care today, cure tomorrow.” The field is littered by the Association’s false claims of progress and assertions that ultimate success is just around the proverbial corner. Boxed in by limited thinking and accumulated power to influence the field, the Association has used fear (appealing to the “loss of self” and financial ruin the condition can engender) to shut off critical examination of its own self-serving behavior and of thinking and valuing in the field in general. It has resolutely failed to lance the aducanumab boil. In fact, the organization is itself a major source of the ongoing inflammation.
The decision by the FDA to approve aducanumab represents the epitome of neoliberal, reductive, market-driven thinking about dementia and is an illustration of the dangers of these ideologies in general. This is what happens when our public policy is shaped by the financial incentives of industry and advocacy groups, who have lost their purpose to help the people they say they represent and pursue the public good. Ironically, recent research has shown that dementia rates have actually been in decline over the past decade in the US and in Western European countries. The reasons have little to do with drug companies and biotechnology, and everything to do with mid-20th century public policy that was aimed at a common good—namely, increasing education via the GI Bill and investment in state colleges and universities, expanded healthcare and improved treatment of risk factors that affect the brain (i.e., vascular disease, high cholesterol, hypertension), remarkably successful smoking cessation programs, deleading gasoline, etc. Collectively, these state actions in service of public health are believed by most experts to have enhanced the resilience of our older neighbors who are advancing through their graying years.
Aducanumab, on the other hand, is an approach foisted upon us by an industry-captured regulatory body that will ultimately serve short-term corporate health rather than population health. In fact, there’s a good chance that this “treatment,” which caused potentially serious side effects like brain swelling and brain bleeds in a disturbing 40% of patients in the initial trials, as well as high rates of headaches, falls, and diarrhea, will impose quite deleterious harms on people. Meanwhile, billions of dollars that could be flowing to 21st century “brain health” measures at the population level (e.g., getting lead out of drinking water, guaranteeing healthcare and higher education/vocational training for everyone) or to providing quality long-term care for every American, will be diverted to industry coffers. More ineffective combinations of drugs and biomarkers are likely to follow the all-too-easy path established by aducanumab. Presumably, as Biogen’s approach and other biologics prove ineffective “experts” will continue telling us that, in order to treat “Alzheimer’s”—which, despite being culturally framed as a singular disease is actually a heterogeneous, multi-factorial syndrome intimately related to aging—we will require “cocktails” of drugs and “panels” of expensive diagnostics. None of this conversation ever considers societal costs (and opportunity costs), or deals with the inconvenient truth that Alzheimer’s, just like brain aging, is highly unlikely to be amenable to a cure.
Ultimately, aducanumab is not an example of “responsible innovation”; it is a product of institutional corruption. It represents not the best of collective human action but the worst—a grotesque outcome guided by an oligarchy of self-serving individual and collective agents. It is time to stop covering up our intellectual and ethical disfigurement, lance this societal boil, and pursue a healthier collective destiny. This means investigating the approval process as politicians and public watchdogs have suggested. It may also mean firing those who do not put the public interest at the heart of their public service. We should not prescribe or pay for this drug, and there should be robust public debate about whether the decision should be reversed. But most fundamentally, with respect to Alzheimer’s, we should place our support behind people, ideas, and plans that actually benefit people with cognitive challenges, their families and society at large.
Peter Whitehouse MD, PhD and Daniel George PhD, M.Sc, are authors of The Myth of Alzheimer’s: What You Aren’t Being Told About Today’s Most Dreaded Diagnosis (St. Martins Press 2008) and American Dementia: Brain Health in an Unhealthy Society (Johns Hopkins Press, 2021). http://www.americandementia.com/