January 2022

The Aduhelm Problem: Greenwall Faculty Scholars Weigh in on New Alzheimer’s Treatment

On June 7, 2021, the Food and Drug Administration (FDA) approved a novel Alzheimer’s treatment called aducanumab, known by its brand name, Aduhelm. The drug was licensed by Biogen Inc. in 2007 and is the first Alzheimer’s drug approved in 18 years. Yet, the FDA’s decision to grant Aduhelm accelerated approval quickly stirred up controversy.

Greenwall Faculty Scholars and Alums have been front and center on this issue, advocating for critical thinking around this drug and its potential impact on the more than six million Americans suffering from Alzheimer’s disease. On social media, in recent publications, and breaking news, Greenwall’s experts are lending their scholarship and voices to urgent discussions about this treatment and whether approving it was the right thing to do.

Questions arise about the FDA’s decision-making process

Greenwall Faculty Scholar Alum, Aaron Kesselheim, MD, JD, a leading regulatory expert and member of FDA’s independent advisory committee for aducanumab, strongly disagreed with the FDA’s decision to approve the drug. Dr. Kesselheim resigned from the committee soon after the FDA announced it would approve Aduhelm, calling the FDA’s action “probably the worst drug approval decision in recent U.S. history.”

Days after resigning, Dr. Kesselheim and fellow Professor of Medicine at Harvard Medical School, Jerry Avorn, MD, published an op-ed arguing the agency had reached “a new low” and has “progressively lowered its standards of effectiveness and safety required for drug approvals.”

For example, the drug’s Phase IV confirmatory trial will take nearly a decade to complete, a timeline Greenwall Faculty Scholars Program Committee Chair and Alum Jason Karlawish, MD and G. Caleb Alexander, MD, argued was “unacceptably long” when the stakes for patients are so high.

Experts have also questioned the FDA’s decision-making process, and the impact it may have on the future of Alzheimer’s drugs. Dr. Karlawish and Joshua D. Grill, PhD, said the decision to grant Aduhelm accelerated approval “disregarded key aspects of scientific process and risks eroding public trust in research, regulatory science and the FDA.” 

But FDA leaders asserted the decision to approve Aduhelm was justified, as patients facing this devastating disease are desperate for treatments. Greenwall Faculty Scholars and Alums, Emily A. Largent, JD, PhD, RN, Andrew Peterson, PhD, and Holly Fernandez Lynch, JD, said that there’s a balance to be found between patient voices and drug safety. “If [the] FDA short-circuits the review process – granting approval earlier and earlier on weaker and weaker evidence – we’ll end up trading good drugs in the future for weak drugs now,” they argue.

Pushback Sparks Congressional Investigation and FDA Review

Since June, there has been a cascade of developments marking Aduhelm as one of the FDA’s most controversial approvals. At $56,000 per year, the price tag of the drug has raised eyebrows. And there are safety questions. Aduhelm must be given as a monthly intravenous infusion, and treatment requires regular MRI scans to monitor for possible brain swelling it could cause.

Following the backlash from patients, providers, and experts, a Congressional investigation of the approval and pricing of Aduhelm was initiated by Rep. Carolyn Maloney and Rep. Frank Pallone, Jr. “We have serious concerns about the steep price of Biogen’s new Alzheimer’s drug Aduhelm and the process that led to its approval despite questions about the drug’s clinical benefit.”

In July, the FDA began to delve into its decision to grant Aduhelm accelerated approval, and updated its guidance to restrict drug use to the population studied in clinical trials – patients with mild memory or cognitive problems. The recommendation reverses the agency’s initial decision to make the drug available to all Alzheimer’s patients, but Prof. Peterson described how changes in labeling could further complicate things for clinicians. “[They] will now have to have difficult conversations about risks and may feel ethically torn about whether they should prescribe,” he said. One day later, acting FDA commissioner Janet Woodcock requested that the Office of Inspector General conduct an independent investigation into the regulator’s decision to approve the drug.

The future of Aduhelm and the FDA in flux

By September 2021, just over 100 patients had been treated with Aduhelm —a sharp contrast to Biogen’s prediction that thousands of patients would soon be using the drug. At the end of December, as the Centers for Medicare and Medicaid Services (CMS) were considering the possibility of coverage for Aduhelm, Biogen announced it would cut the price of Aduhelm in half. Effective January 1, 2022, the cost of Aduhelm would drop from $56,000 a year to $28,200. The company said it hoped the price cut would expand access to the drug. 

 On January 11, 2022, CMS released a preliminary decision about coverage for Aduhelm, stating that the agency would only provide coverage for Aduhelm and similar drugs for people enrolled in qualifying clinical trials. Many experts, including Prof. Fernandez Lynch and Dr. Karlawish, expressed that CMS made an appropriate decision.

Regardless of how the controversy shakes out, the FDA’s decision to grant Aduhelm accelerated approval will impact the agency’s decision-making as well as patients and caregivers affected by Alzheimer’s for years to come.

With rigorous scholarship and vigilant attention to this issue, Greenwall Faculty Scholars continue to shine a light on profound moral and ethical issues surrounding Aduhelm. Follow more work and commentary from our Greenwall Faculty Scholars on this and other issues on our blog and visit us on Twitter for updates on this developing story.