Three decades ago, a small group from within the AIDS activist organization ACT UP changed the course of medicine in the United States. They employed what they called “the outside/inside strategy.” The activists staged large, noisy demonstrations outside the Food and Drug Administration and other federal government agencies, demanding an acceleration of the drug-approval process. Others learned the minutiae of the science and worked quietly with receptive bureaucrats, bringing the patient’s perspective to the table toward the same goal of faster drug approval.
These were desperate young people dying from a new disease for which there were few treatments and no cure. At first, federal bureaucrats and drug companies resisted, but eventually more AIDS drugs became available.
“Biogen, the FDA, and Alzheimer’s Association are preying on desperate hopes of families like ours.”
The push by AIDS activists for an effective treatment was a breakthrough in the medical industry. It showed the power of a grassroots movement to spur the government and Big Pharma to action. But it had a dangerous and lasting side effect. Over the ensuing decades, pharmaceutical companies learned that with the backing of patient advocacy groups, they could get more drugs approved more quickly with less robust data. The drug-approval process slackened considerably, and the result has been many products with minimal effectiveness generating enormous profits.
This trend, according to scientists, reached its nadir with the recent approval of Aduhelm (also known by its generic name aducanumab), a treatment for Alzheimer’s disease from the biotech company Biogen. The F.D.A. approved the treatment following intense lobbying by the Alzheimer’s Association patient group. A recent report from the Alzheimer’s Association reveals that it received a $275,000 donation from Biogen in 2020. Eisai, a Japanese company that partnered in the development of the drug, gave $250,000 in 2020. The Association also received large donations from other companies hoping to bring their own, similar, Alzheimer’s drugs to market.
The F.D.A.’s decision is “abominable,” said Peter B. Bach of Memorial Sloan Kettering Cancer Center, an expert on drug policy and pricing. He told me the decision will lead to companies and lobbyists “acting as the arbiters of what is safe and effective,” and a health care system that is “more opaque, more inequitable, and deeply subject to conflicting financial and political interests.”
Biogen originally declared the two critical Phase III trials of the drug failures. In fact, the company stopped the trials, and its C.E.O. Michel Vounatsos said, in a statement, “This disappointing news confirms the complexity of treating Alzheimer’s disease and the need to further advance knowledge in neuroscience.”
But then Biogen resubmitted the same data to the F.D.A. The agency allowed the drug on the market under its “accelerated approval” rules. The process, initiated by the AIDS activists, allows drugs to be approved when some “biomarker,” usually a chemical or cellular change, indicates there might be a benefit. In this case, the biomarker is a drop in amyloid, a chemical that can build up in the brains of some Alzheimer’s patients. For decades, scientists have intensely debated whether amyloid causes Alzheimer’s.
In its statement after the approval, the F.D.A. said the drop in amyloid “is expected to lead to a reduction in the clinical decline of this devastating form of dementia.” The F.D.A. statement also said that in one of the two groups studied, there was a reduction in clinical decline (no one improved), but not in the other. Alzheimer’s experts disagree. Sam Gandy, a professor of Alzheimer’s Disease Research at Mount Sinai Medical Center, told me the trial was essentially uninterpretable, “and that’s why it failed.”
Before the F.D.A. approves a drug, it convenes a panel of experts to issue a recommendation for action. The agency is not obliged to follow the panel’s instructions, but usually does. In this case, the expert panel voted 10 to 1 against approval. Since then, three members of the panel have resigned. One who resigned, Aaron Kesselheim, a professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, told the New York Times, “This might be the worst approval decision that the F.D.A. has made that I can remember.”
The cost of Aduhelm for Medicare will be more than the annual budget of NASA.
In its approval statement, the F.D.A. acknowledged the panel’s advice. “After the Advisory Committee provided its feedback, our review and deliberations continued, we decided that the evidence presented in the Aduhelm application met the standard for Accelerated Approval. We thank the Advisory Committee for its independent review of the data and valuable advice,” the statement read.
All of the 3,200 volunteers in Biogen’s two trials had early stage disease. But in its approval, the F.D.A. allowed the drug to be prescribed to anyone from those just beginning to show symptoms to those with advanced symptoms, including dementia. In the U.S. alone, that encompasses almost 6 million people.
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Under U.S. law, drug companies can charge whatever they want for any product. Biogen has announced Aduhelm will sell for $56,000 a year for each patient, but that is only about half the cost of taking it. Since it is a large protein, it must be administered by infusion in a specialized center, and it requires intense, expensive medical monitoring. Medicare will pick up much of these costs for a large percentage of people taking the drug. But U.S. law prohibits Medicare from negotiating prices.
Many Alzheimer’s experts predict demand for the drug will be enormous. “Even the most sophisticated patients in my private practice who have enrolled in clinical trials [of] experimental Alzheimer’s drugs that work in similar ways as Aduhelm, are unable to resist the pull of desperation potentiated by the false hope engendered by Aduhelm’s approval,” Gandy, of Mount Sinai, wrote in STAT. “They are rushing to resign from their current trials and queuing up to start Aduhelm infusions.” An analysis by the New York Times predicts that the cost of Aduhelm for Medicare will be more than the annual budgets of NASA or the EPA.
There is a chance that this most questionable of F.D.A. actions could lead to some positive outcomes. The F.D.A. granted the approval as “conditional.” At some point in the future, Biogen is supposed to follow people taking the drug and provide evidence that it improves cognition, or at least stops the decline for a significant period of time. In the past, the F.D.A. has granted such conditional approval for other drugs—especially treatments for cancers. Congressional oversight could assure that the conditions are in fact met, and approval is quickly yanked if they are not.
In the 1980s, Gregg Gonsalves was an ACT UP activist on the frontlines. Today he is an assistant professor of epidemiology at the Yale School of Public Health. His father, who suffered from dementia, died two years ago, and he understands the enormous desire for Alzheimer’s treatments. But he said Aduhelm is not one. “Biogen, the F.D.A., and Alzheimer’s Association are preying on desperate hopes of families like ours,” Gonsalves said. When ACT UP was fighting for AIDS treatments, he explained, “We didn’t foresee the deep cynicism of the industry. Our fight for speedier F.D.A. approval, for robust, expanded access programs before approval, was never meant to foreclose on getting information about the drugs we put in our bodies.”
Robert Bazell is an adjunct professor of molecular, cellular, and developmental biology at Yale. For 38 years, he was chief science correspondent for NBC News.