The fate of a potential new Alzheimer’s drug is still uncertain. Evidence that the drug works isn’t convincing enough for it to be approved, outside experts told the U.S. Food and Drug Administration during a Nov. 6 virtual meeting that at times became contentious.
The scientists and clinicians were convened at the request of the FDA to review the evidence for aducanumab, a drug that targets a protein called amyloid-beta that accumulates in the brains of people with Alzheimer’s. The drug is designed to stick to A-beta and stop it from forming larger, more dangerous clumps. That could slow the disease’s progression but not stop or reverse it.
When asked whether a key clinical study provided strong evidence that the drug effectively treated Alzheimer’s, eight of 11 experts voted no. One expert voted yes, and two were uncertain.
The FDA is not bound to follow the recommendations of the guidance committee, though it has historically done so. If ultimately approved, the drug would be a milestone, says neurologist and neuroscientist Arjun Masurkar of New York University Langone’s Alzheimer’s Disease Research Center. Aducanumab “would be the first therapy that actually targets the underlying disease itself and slows progression.”
Developed by the pharmaceutical company Biogen, which is based in Cambridge, Mass., the drug is controversial. That’s because two large clinical trials of aducanumab have yielded different outcomes, one positive and one negative (SN: 12/5/19). The trials were also paused at one point, based on analyses that suggested the drug didn’t work.
Those unusual circumstances created gaps in the evidence, leaving big questions in some scientists’ minds about whether the drug is effective. Aducanumab’s ability to treat Alzheimer’s “cannot be proven by clinical trials with divergent outcomes,” researchers wrote in a perspective article published November 1 in Alzheimer’s & Dementia. The drug should be tested again with a different clinical trial, those researchers say.
But other groups, including the Alzheimer’s Association, are rooting for the drug. In a letter sent to the FDA on October 23, the nonprofit health organization urged aducanumab’s approval, along with longer-term studies of the drug.
“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,” Joanne Pike, chief strategy officer of the Alzheimer’s Association, wrote in the letter. She noted that by 2050, more than 13 million Americans 65 and older may have Alzheimer’s. More than 5 million Americans currently have the disease.
Even with an eventual approval, questions would remain for patients and their caregivers, says Zaldy Tan, a geriatric memory specialist at Cedars-Sinai Medical Center in Los Angeles. “Cost and logistics are going to be complex issues to tackle,” he says. One estimate puts aducanumab’s price tag at $40,000 annually, and treatment would require injections, for instance, which would require regular visits to a health care facility.