After several months of delay, in June, the FDA approved a new drug, aducanumab, for treating early-stage Alzheimer’s disease in the hopes of slowing – if not reserving – cognitive decline.
This medication is the first drug in nearly 20 years that targets the pathophysiology of Alzheimer’s disease, not just the symptoms.
Aducanumab will go under the name Aduhelm. Developed by Biogen laboratory, Aduhelm has shown in clinical trials to reduce amyloid-beta protein – a sticky plaque, which builds up in the Alzheimer’s brain and is a hallmark of the disease.
However, even though amyloid proteins were reduced in the trials, there was no strong evidence that it had much impact on patients’ cognitive abilities.
Ten of the 11-member FDA advisory committee, along with an independent panel of prominent doctors and scientists that reviewed the clinical trials, said the evidence “raised significant doubt about whether the drug is effective.”
The crux of the controversy involved two Phase 3 trials with results that contradicted each other: One suggested the drug slightly slowed cognitive decline while the other trial showed no benefit. The trials were stopped early by a data monitoring committee that found the drug did not appear to be showing any benefit.
“There’s so little evidence for effectiveness,” said Lon Schneider, MD, director of the California Alzheimer’s Disease Center at the University of Southern California, who helped conduct one of the aducanumab trials. He added, “I don’t know what caught the FDA’s fancy here.”
Aduhelm will be administered through monthly infusions at the cost of $56,000 annually. Patients must also undergo expensive brain imaging and other diagnostics, most likely to cost tens of thousands of dollars.
Side effects can include swelling and bleeding in the brain. Nausea, confusion and other side effects also can occur.
Why did the FDA approve the drug?
“We examined the clinical trial findings with a fine-tooth comb; we solicited input from the Peripheral and Central Nervous System Drugs Advisory Committee; we listened to the perspectives of the patient community, and we reviewed all relevant data,” writes Patrizia Cavazzoni, MD, director of the Center for Drug Evaluation and Research at the FDA, on the agency website.
“We ultimately decided to use the Accelerated Approval pathway — a pathway 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.
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.”
After initial trials were suspended, Biogen said that it later analyzed additional data and concluded that in one of the trials, a high dose could delay cognitive decline by 22 percent or about four months over 18 months. In the trial’s primary measurement, the high dose appeared to slow decline by 0.39 on an 18-point scale rating memory, problem-solving skills and function.
But a lower dose in that trial, and high and low doses in the other, showed no statistically significant benefit over a placebo.
In all studies in which it was evaluated, however, Aduhelm consistently reduced the level of amyloid plaques in the brain in a dose and time-dependent fashion. The expectation is that the reduction in amyloid will result in a reduction in clinical decline.
Stephen Salloway, MD, who has received research and consulting fees from Biogen but was not paid for being an aducanumab trial site principal investigator, said that while he understood the concerns about the data, “the totality of the evidence favors approval, and FDA approval will open the door to a new treatment era for Alzheimer’s disease that we can build on.”
“The need for treatments is urgent: right now, more than 6 million Americans are living with Alzheimer’s disease, and this number is expected to grow as the population ages. Alzheimer’s is the sixth-leading cause of death in the United States,” said Cavazzoni.
Alzheimers Coachella Valley is a community resource for dementia support and education. For more information, call (760) 776.3100 or visit www.cvalzheimers.org.