By Marcia Angell Jun 22, 2021, The Santa Fe New Mexican
Prescription drugs cannot be sold in the U.S. without FDA approval. Approval is usually based on at least two company-sponsored clinical trials that show safety and effectiveness, called positive trials. Normally one of the FDA’s standing advisory committees, which consist of independent experts from academic institutions around the country, evaluates the evidence. It then votes on whether the new drug should be approved, and the FDA almost always follows that advice.
In the case of Aduhelm, nothing like that happened. Instead of the usual two positive clinical trials, Biogen (the company that makes Aduhelm) submitted one positive and one negative trial. Even the positive trial showed only marginal benefits with significant side effects, including brain swelling and hemorrhages. The FDA’s relevant advisory committee — the Peripheral and Central Nervous System Drugs Advisory Committee — voted overwhelmingly against approval. Since then, three members of the committee have resigned in protest against the FDA decision to approve the drug anyway.
When the FDA overruled its own panel of experts, it made approval conditional on Biogen conducting another clinical trial after Aduhelm is already on the market. The FDA sometimes grants this sort of conditional approval for important drugs, but companies seldom complete these “commitment” studies. Although the FDA may then pull the drug from the market, it has never done so. Thus, Aduhelm is almost certainly on the market to stay, no matter how useless and how many side effects.
About 6 million Americans are now afflicted with Alzheimer’s disease, and the prevalence is rising. With no treatment available (other than a few drugs to delay symptoms), these patients and their families will naturally want to try Aduhelm. Because it’s received FDA approval, clinicians will be reluctant not to prescribe it.
Biogen intends to charge about $56,000 per year initially. The price will almost certainly increase, as it always does for top-selling drugs. Adding to the costs are the facts that the drug must be given in monthly intravenous infusions, and repeated brain scans are recommended to check for brain swelling and hemorrhage.
Because most patients with Alzheimer’s disease are over 65, Medicare will be on the hook for much of the costs. But Medicare is not free to patients (as originally intended when it was enacted in 1965). Its out-of-pocket costs are rising, as they are for private supplementary insurance. One way or another, the enormous expenditures for Aduhelm will come from our pockets in the form of rising premiums, deductibles and copayments.
Some might respond that Alzheimer’s disease is a terrible and incurable condition, so why not approve any drug that has any chance of success? But that argument underscores the necessity of getting it right, not putting unproven remedies on the market. After all, cancer is also often incurable, but we still require treatments to be based on reasonable evidence from clinical trials and to meet the standards of the FDA advisory committee. The very magnitude of the need should argue against dropping standards.
Moreover, if millions of people are taking Aduhelm, it will be nearly impossible to conduct clinical trials of more promising drugs, since people taking Aduhelm will not be eligible for a clinical trial of a new drug compared with a placebo. Thus, doing the necessary studies to find a genuinely effective treatment will be difficult.
Why would the FDA approve a drug based on flimsy and contradictory evidence, against the recommendation of its advisory committee? One possible explanation is the growing closeness of the agency with the industry it is supposed to regulate. In fact, the FDA has actually been on the payroll of the pharmaceutical industry since 1992, when Congress enacted the Prescription Drug User Fee Act.
The measure requires drug companies to pay fees to the FDA for each new drug application it reviews. The more drugs reviewed and the faster it’s done, the more income for the FDA. These fees now account for more than half of the support for the FDA’s center that reviews new drugs. If you are an FDA drug reviewer and your salary is paid mainly by drug companies, you will naturally be tempted to smile favorably on their drugs. But it’s a clear conflict of interest, and it should be seen as such.
As enacted, the Prescription Drug User Fee Act must be reauthorized every five years, and it’s due next year. It’s time to let this harmful law sunset. The FDA is a vital public agency, and it should be supported entirely by the public and serve only the public. It should not be the captive of the industry it regulates.
Aduhelm will be a blockbuster drug, with annual sales of billions of dollars. But the biggest cost will be that millions of Americans, victims of falsely generated hope, will be taking a drug not shown to be safe and effective, while the development of a truly effective treatment will be delayed.
Dr. Marcia Angell is the former editor-in-chief of the New England Journal of Medicine and author of the Random House book, The Truth About the Drug Companies. She lives in Santa Fe.