Alzheimer’s furor shows US health system’s flaws

Patients and their families may see hope in the news that the Food and Drug Administration (FDA) has approved a drug to slow the pace of Alzheimer’s disease. Aducanumab is the first medicine authorised to treat what might be an underlying cause of the disease: amyloid beta clumps that accumulate in the brain. Yet the evidence from clinical trials that this drug reduces Alzheimer’s is incomplete; it may be only minimally effective, if it works at all. The FDA’s own expert panel strongly objected to the drug’s approval.
All of which makes the FDA’s announcement both perplexing and wrong. It threatens to mislead millions of Alzheimer’s patients. At the same time, because Biogen plans to price the drug at $56,000 a year for the average patient, it also stands to cost Medicare and other insurers a bundle. This underlines the need for two kinds of reform. First, the FDA needs to rethink its processes for approving drugs. Second, the rules controlling how Medicare chooses and pays for medicines need a thorough overhaul.
The FDA has failed to fully explain why it overruled the almost unanimous advice of its advisory panel on aducanumab. The agency didn’t deny that the clinical-trial evidence was poor. It simply ignored that problem and used different reasoning to grant the drug “accelerated approval.” To the general public, this term suggests urgent approval of an especially valuable treatment.
In fact, it’s a more limited endorsement than ordinary approval, indicating that the drug has not proven a “real effect on how a patient survives, feels or functions,” in the FDA’s words, but nevertheless acts on an underlying disease process in a way that might predict such a benefit.
The FDA noted that patients who received aducanumab in the drug’s two truncated trials experienced a significant reduction of amyloid plaque, while those in the control arms did not. If the amyloid hypothesis is correct, the loss of plaque might cause a lessening of Alzheimer’s disease.
A problem with this reasoning is that other experimental drugs that have targeted amyloid plaques have failed their clinical trials, and now many experts question whether plaque is a good predictor of Alzheimer’s disease progression. Yet the FDA settled on accelerated approval without seeking comment from outside experts or fully explaining its thinking on the plaque question.
The agency has asked the manufacturer, Biogen, to conduct another trial within eight years — and says that if no real benefit is seen, it may withdraw approval. But that won’t be easy.
Now that the FDA seems to have said aducanumab works, it will be difficult to recruit subjects for a trial in which half the patients are given placebos. For this reason alone, the essential first step is for the FDA to help patients understand its announcements. Accelerated approval doesn’t mean the drug is any good.
Despite that, Biogen will sell aducanumab — under the brand name Aduhelm — at an exorbitant cost. An estimated 1.2 million to 1.4 million Americans with Alzheimer’s stand to be given the medicine, because they have mild cognitive impairment and plentiful amyloid deposits.

—Bloomberg