Artist's rendering of a brain cell damaged by amyloid beta plaque in Alzheimer's disease

In a landmark decision, the Food and Drug administration has approved the Alzheimer’s disease drug aducanumab (Brand name: Aduhelm). The decision sets the stage for it to become the first-ever drug marketed to slow progression of the brain-wasting disease, according to developer Biogen.

The FDA had not approved a new Alzheimer’s drug since 2003 and various experts have stacked up against this one, including at least a few leading long-term care experts.

With this approval, clinicians say they may be caught between concerns about aducanumab’s efficacy, safety, accessibility and affordability, and the needs of patients who feel they have no other recourse. 

“The FDA’s decision is an unfortunate and ill-advised one” for residents with Alzheimer’s and their families, Karl E. Steinberg, M.D., president of AMDA – The Society for Post-Acute and Long-Term Care Medicine, told the McKnight’s Clinical Daily

“There are so many factors that make it a bad choice,” he said. The drug has limited effectiveness considering its potential dangers, he added. It is not yet clear how the drug will be rolled out and to which populations initially, and it is expected to be expensive for some patients and for Medicare.

Although as a geriatrician he sympathizes with persons with dementia and family members who are desperate for an effective treatment, Steinberg said he would not be comfortable recommending the drug, and would not personally prescribe it at this time. “I see the devastation that [Alzheimer’s] wreaks every day, but this is not the answer to that,” he added.

“I don’t think it will be as much of an issue in skilled nursing facilities [due to initial lack of access], but I do think that there will be a not insubstantial population who will be clamoring for it. I know there are a lot of doctors who have said they will not prescribe it.”

Other long-term care physicians agree.

“I know that people with a chronic and terminal disease like Alzheimer’s can be desperate to try anything that might modify the course of the disease, but I think the evidence for the efficacy of aducanumab is quite limited,” Kevin O’Neil, M.D., FACP, CMD, chief medical officer of ALG Senior, told the McKnight’s Clinical Daily

“It is certainly not a cure for Alzheimer’s disease and likely won’t be helpful in those with advanced disease. Personally, I would wait for more research to prove its efficacy and safety,” the senior living physician added. “Also, it needs to be affordable. Out-of-pocket costs for the drug could be thousands of dollars.”

But other elder advocates back the FDA’s decision, including the Alzheimer’s Association. “We believe people should have that access and ability to decide for themselves today, not four or five years from now when another phase 3 trial can be done,” said Chief Science Officer Maria Carillo, Ph.D., according to pharmaceutical news outlet Fierce Pharma.

“This treatment, while not a cure, is pivotal and current progress in science is significant. We expect this will be the first of a number of treatments to come,” the association stated on its website, calling the approval a victory for patients and families. “Aducanumab addresses the disease in a way that has never been done before. This therapy slows progression of the disease, rather than only addressing symptoms.”

A rough clinical trials process

The clinical trials process has been bumpy, with conflicting results. In fact, the agency’s decision was made despite a vote against approval by its own independent advisors. But FDA leaders ultimately decided that Biogen’s application met the requirements for an established accelerated pathway to approval, it said in today’s announcement.

“In determining that the application met the requirements for accelerated approval, the Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy,” FDA stated.

“In all studies in which it was evaluated … Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion.  It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” the FDA said.

The drug is administered via monthly infusions, and safe treatment protocol may require regular brain scans to guard against side effects that may include bleeding and swelling in the brain. It works by removing amyloid beta, according to Biogen. One phase 3 trial in adults was halted due to lack of efficacy. But another trial using a higher dose of the drug showed reduced decline in cognition, memory, language and activities of daily living performance in adults with early stage disease. Cognitive decline was delayed by about 22% over 18 months, the company reported. 

A panel of FDA advisors voted against approving the drug in November 2020, with some pointedly reaffirming that position ahead of today’s FDA decision deadline. Critics said there is not enough persuasive evidence to support its approval without more clinical trials. 

But patients’ advocates have argued that, with few existing alternatives and no other new treatments immediately in sight, the signs of potential benefits are enough to allow patients access to the drug.

Biogen required to conduct a post-approval trial

The FDA’s chosen approval process appears to be an attempt to balance these competing concerns. Accelerated approval is intended to “provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit,” the agency said in a statement. 

The agency is also requiring Biogen to conduct a post-approval clinical trial to verify the drug’s benefits. “If the drug does not work as intended, we can take steps to remove it from the market. But hopefully, we will see further evidence of benefit in the clinical trial and as greater numbers of people receive Aduhelm,” FDA said. 

Biogen, in fact, recently announced the launch of a new Phase 3 clinical trial to determine long-term safety and efficacy. The trial, called EMBARK, is a re-dosing study of aducanumab in patients with Alzheimer’s who took part in earlier clinical studies of the drug. 

In the 24-month study, participants will receive 10 mg/kg aducanumab via infusion every four weeks, according to Biogen. EMBARK is expected to be one of the largest clinical trials involving Alzheimer’s disease, with a planned enrollment of 2,400 participants, the company said.