U.S. approval of a medication that removes a key marker for Alzheimer’s disease sharply divided clinicians and advocates over whether it has the ability to change the disease’s progress and how it will be used.
Biogen Inc.’s aducanumab was approved by the U.S. Food and Drug Administration Monday based on its ability to remove amyloid plaques in the brain, long seen as a surrogate for the mind-robbing disease that’s been diagnosed in about 5.7 million Americans. The accelerated approval requires added study of the drug and leaves open the chance it could be taken off the market if it fails to show true benefit.
The decision came despite opposition from the FDA’s independent advisory committee, and with the agency saying that evidence from clinical trials was incomplete on the drug’s effectiveness. Still, one thing is clear: Having the drug on the market will change Alzheimer’s care, at least for some patients, and the FDA’s green light might pave the way for future therapies.
”It’s simply a new day for people facing Alzheimer’s, and we do believe that this will actually drive more innovation and investment,” said Harry Johns, chief executive officer of the Alzheimer’s Association.
The approval is the first clearance of an Alzheimer’s therapy by the FDA since 2003. Those earlier drugs reduce symptoms but don’t slow down the disease’s progression.
Noting there “will be challenges” to getting the drug broadly used, Johns said his organization is dedicated to “getting people access, and that will apply to a variety of issues to get them to their doc, to be detected, ultimately accurately diagnosed, and then treated appropriately.”
Broad Use
Though the clinical trials enrolled patients who had mild cognitive impairment due to Alzheimer’s, the FDA said it approved aducanumab to be used broadly for treatment, with little specification about what subset of patients it may be appropriate for.
“It’s now going to be a question of how doctors are going to respond to that invitation,” said George Vradenburg, chairman and co-founder of the nonprofit UsAgainstAlzheimer’s.
It also means a bigger role for gatekeepers like the Medicare program and private insurers. The FDA has “essentially shifted the responsibility of defining the patients to the payer community,” said Steve Miller, chief clinical officer at insurer Cigna Corp.
“I was anticipating a bit more direction from the FDA than what the label indicates,” he said. Most insurers will likely stick closely to the trial criteria of early stage signs of cognitive impairment, along with brain scans or other tests to confirm the presence of amyloid, a biological marker of Alzheimer’s, Miller said.
He said he expects the initial number of patients treated in the first year to be in the tens of thousands, rather than the millions.
Given the older population that Alzheimer’s affects, how Medicare decides to cover the drug and associated testing will be crucial. The agency didn’t respond to questions Monday. It had previously said it was evaluating the drug in the event it was approved.
Surrogate Endpoints
Studies of so-called surrogate endpoints are typically used when measuring the drug’s benefit on illness or mortality might take too long. Biogen’s trials — which resulted in contrasting outcomes — were designed to measure the progression of the disease.
“Here we’d already done the trials looking at clinical outcomes,” with one large trial negative and another slightly positive, said David Rind, chief medical officer at the Institute for Clinical and Economic Review, a nonprofit that evaluates the costs and benefits of medicines. “Going back to the surrogate doesn’t make a lot of sense.”
Approving a drug because it removes a marker like amyloid plaques “seems concerning,” Rind said.
FDA Credibility
Public Citizen’s Health Research Group, an advocacy organization, expressed similar concerns, and said the FDA credibility has been damaged by the decision.
“The approval was based on seriously flawed analyses of two identical phase 3 trials that were stopped at the halfway point because a preliminary review of the data found that the trials, if continued to completion, were unlikely to show the drug benefited Alzheimer’s patients,” the group said in a statement.
“One trial showed no benefit, and the other only suggested possible minimal benefit at a high dose,” the group said. The approval could raise false hope in patients, the statement added, and “potentially bankrupt the Medicare program because of the drug’s projected exorbitant price.”
Biogen plans to sell the therapy under the brand name Aduhelm. It will cost $56,000 a year, Biogen and its Tokyo-based partner Eisai Co. Ltd. said in a statement. Cigna Corp. has agreed to a value-based pricing agreement with Biogen intended to make it easier for patients to access the therapy.
Open Door
If the FDA is willing to accept reduction in amyloid as sufficient evidence for approval, “that may open the door to other drugs,” said Erik Musiek, a neurologist at Washington University in St. Louis. “If clearing plaques is all you need, that would be a different ballgame for sure.”
He was heading into the clinic Monday afternoon. The approval of the drug meant that, for some patients, “it’s going to be a very different conversation.”
While the drug won’t be appropriate for many patients because their disease has progressed too far, he said, for people with early signs of impairment, the medication might push them to get a firm diagnosis of Alzheimer’s earlier.
Muziek said the FDA was in a difficult position. “If you say, let’s do another clinical trial, it’s five more years,” he said. “It’s a whole generation of people with Alzheimer’s who are never going to get this treatment.”
Howard Fillit, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the FDA threaded the needle between the need to gather more evidence and the desire to give patients access to a therapy that might help.
“I think that they prioritized the unmet patient need and found a good compromise, basically, which I think was scientifically driven and also a compassionate decision,” he said in an interview.
