An estimated 6.2 million Americans—most over age 65—currently live with Alzheimer’s disease or Alzheimer’s-related dementia. As our population ages, this number is projected to nearly triple to 14 million people by 2060, placing an even greater burden on patients, caregivers, and the healthcare system.
With no known cure for Alzheimer’s, the Food and Drug Administration (FDA) has stepped up its efforts to find more effective treatments for the disease—recently approving the new drug Aducanumab (Aduhelm) for those with mild disease.
In the following Q & A, Steven Woloshin, MD, MS, a professor of medicine and community and family medicine, and co-director of the Master of Health Care Delivery Science program at The Dartmouth Institute for Health Policy and Clinical Practice, discusses the controversy surrounding the new drug’s approval. Woloshin and colleague Aaron Kesselhim, MD, JD, MPH, a professor of medicine at Harvard Medical School, explain the potential benefits and harms of Aducanumab in this month’s JAMA Internal Medicine Patient Page.
Q: What has made the FDA’s approval of Aducanumab so controversial?
Woloshin: In the two clinical trials the FDA used as the basis of approval, Aducanumab was shown to reduce visible plaques in the brain, a main feature of Alzheimer disease.
But that didn’t translate to any clinical effect that would be noticeable for most patients or families. At the same time, some serious potential harms, including brain swelling and bleeding, were common with the drug. While most cases were mild and required only dose adjustments, 1% to 2% of patients required hospitalization or had lasting complications. Aducanumab is also very expensive to administer (even after the company halved the price, it is still listed to cost about $28,000 per year).
For these reasons, many people didn’t understand why the FDA chose to approve it. In fact, when an advisory panel (which included Dr. Kesselheim) was convened by the FDA (prior to approval) to review Aducanumab, they voted 10 to 0 (with one abstention) against approving it—citing the lack of evidence that the modest potential benefits could be reconciled against the important potential harms and its high price.
Q: You created the Drug Facts Box, with your wife and research partner Lisa Schwartz, MD, MS, who passed away in 2018. Why is it an important tool to use when evaluating new drugs like Aducanumab?
(note: the Aducanumab Drug Facts Box is posted on the Lisa Schwartz Foundation for Truth in Medicine website: https://lisaschwartzfoundation.org/drug-fact-boxes/).
Woloshin: Lisa and I developed the Drug Facts Box to help people make informed decisions about prescription drugs. It contains brief summaries of benefit and harm data for each FDA-approved use of a drug. A series of studies—including national randomized trials—demonstrates that most consumers understand the Drug Facts Box and that it improves decision-making.
Q: What’s the most common misperception about Aducanumab?
Woloshin: I think some people assume that it works better than it does—that it will meaningfully slow down or stop progression or even cure the disease. It hasn’t been shown to do any of these things.
Based on the available evidence, I think we can’t even say that the likely benefits outweigh the harms. We just don’t know yet. The studies that were done were not that long—12 to 18 months—so it’s possible that over time the benefit/harm ratio may change. For that reason, the FDA is requiring the company that makes the drug to do a proper, long-term study to define the actual long-term benefits and harms.
But that study doesn’t have to report results until 2030. In the meantime, there are some serious open questions that remain about this drug and how well it works. I really think that the FDA should have waited for more information before moving ahead with this approval.