A federal panel will decide on Friday whether to recommend approval of a controversial but potentially promising Alzheimers drug, which would be the first to come to market in nearly two decades.
The drug, aducanumab, would not stop or reverse dementia, but some evidence suggests it can slow the progression of memory and thinking problems in people with mild or early symptoms of cognitive decline, giving them a little extra time before they develop Alzheimer’s. It would be the first medication to do so by attacking the core biology of Alzheimer’s disease.
Many Alzheimer’s experts, however, are skeptical that aducanumab, made by Biogen, has exhibited strong enough evidence that it can slow cognitive decline. The drug — given as a monthly intravenous infusion — would also be costly, about $50,000 a year. And some experts say that it would be challenging for doctors trying to appropriately prescribe and monitor its use and that approval of such a drug would make it less likely that patients would participate in studies for other Alzheimer’s drugs that might ultimately work better.
The drug’s path through clinical trials has been rocky, with only one of two Phase 3 trials showing positive results — and those results emerged only from an analysis of additional data after the trials were stopped in March 2019 by an independent data monitoring committee because the drug didn’t appear to be working.
Several experts, including a Mayo Clinic neurologist who was a site investigator for an aducanumab trial, have said that the evidence is too weak for the drug to warrant approval now and that another rigorous clinical trial should be conducted before a decision is made on whether the drug should be made available.
“Perfection may be the enemy of the good, but for aducanumab, the evidence doesn’t even rise to ‘good,’” the neurologist, Dr. David Knopman, wrote in a comment submitted to the panel before Friday’s hearing. Dr. Knopman, who sits on the advisory panel but was recused from the hearing because of his work with the aducanumab trials, added, “Contrary to the hope that aducanumab will help Alzheimer patients, the evidence shows it will offer improvement to none, it will harm some of those exposed, and it will consume enormous resources.”
The panel, a committee of medical experts that advises the Food and Drug Administration, will review evidence of the effectiveness and safety of aducanumab. If it endorses the drug on Friday, that would not guarantee its approval, but the F.D.A. often follows the recommendations of its advisory panels.
Nearly six million people in the United States and roughly 30 million globally have Alzheimer’s disease, a number that is expected to more than double by 2050. If approved, aducanumab could serve as a potential medication for the roughly two million Americans estimated to have mild Alzheimer’s-related cognitive decline.
Its availability would have striking implications — not only for patients, but for doctors, researchers and other drug companies and for health care costs. It would also be a blockbuster drug for Biogen.
Aducanumab is a monoclonal antibody that targets the beta amyloid protein that clumps into plaques in Alzheimer’s disease. Many other drugs that reduce amyloid accumulation have not been shown to help symptoms, so if aducanumab is determined to be effective, it would support a long-held theory that attacking amyloid can help if done early enough in the disease process, when memory and cognitive difficulties are still mild.
Documents posted by the F.D.A. in advance of the hearing gave the impression that most of the agency’s reviewers were satisfied that data from the successful trial was strong and that safety issues, which mostly involved a type of brain swelling, were manageable.
“The applicant has provided substantial evidence of effectiveness to support approval,” Kevin Krudys, an F.D.A. clinical analyst in neurology, wrote in a presentation sent to the committee.
But another F.D.A. reviewer expressed concerns in the documents. Tristan Massie, an F.D.A. mathematical statistician, wrote that he believed “there is no compelling, substantial evidence of treatment effect or disease slowing and that another study is needed.”
Other experts said that the degree of benefit the trial claims to show is slight, slowing decline over 18 months by half a point on a 3-point cognitive scale.
“My view is that it doesn’t do anything,” said Dr. Michael Greicius, medical director of the Stanford Center for Memory Disorders, adding that he might discourage his patients from taking it. “For people who are saying, ‘Oh, come on, it’s OK — if it helps a little bit, why not give it to people?’ my response is there’s no data to tell me that this medicine works in Alzheimer’s.”
The Alzheimer’s Association, on the other hand, wrote a letter to the panel supporting approval. It said the F.D.A. should require a post-marketing study but should make the drug to be available while that occurs.
“While the trial data has led to some uncertainty among the scientific community, this must be weighed against the certainty of what this disease will do to millions of Americans absent a treatment,” wrote Joanne Pike, the association’s chief strategy officer. “The potential to delay decline would be denied to millions, and that time lost for those spouses, partners, moms, dads, grandmothers, grandfathers, aunts, uncles, friends, and neighbors cannot be recovered. In the balance of these considerations, we urge approval.”
Dr. Eric Reiman, executive director of the Banner Alzheimer’s Institute, who has been a co-leader on studies with other anti-amyloid drugs but not with aducanumab, said the advisory panel was being confronted with a “very unusual and important” situation, since the clinical trials were discontinued before their scheduled completion in 2021, when the findings might have been more definitive.
“They have a Solomonic decision to make, with one study that demonstrated very promising effects and the other study that didn’t demonstrate an effect,” he said. “I think it’s a challenging decision, because everybody wants to do what’s best for patients and families.”
