Count this among the biggest worries of our age: our minds slowly being lost to Alzheimer’s. The dread is so strong that we analyze every case of lost keys or names that stay on the tip of our tongues for its potential foretelling of a brain breakdown. So the news this week that the Food and Drug Administration has approved a new Alzheimer’s drug, called Aduhlem, is pretty momentous for the six million people in the U.S. who suffer from the debilitating disease. But what can and can’t the drug do?
“We feel a great sense of purpose and responsibility to turn the hope of today’s FDA approval of ADUHELM into a reality for people living with Alzheimer’s disease and their families,” said Alisha Alaimo, president of the drug’s maker, Biogen U.S. “We are committed to access and health equity as top priorities and will continue working with multiple stakeholders with the goal of helping patients who may benefit from treatment obtain care as quickly as possible.”
How Does Aduhlem Work?
Aduhelm is the first new treatment approved for Alzheimer’s since 2003 and is the first FDA-approved treatment directed at the underlying pathophysiology of Alzheimer’s disease, the presence of amyloid beta plaques in the brain. The drug is not a cure and does not reverse the disease’s progression. In clinical trials, success was measured not by cognitive improvement but by slowing in the rate of cognitive and functional decline.
The drug is not a cure and does not reverse the disease’s progression.
Researchers evaluated Aduhelm’s efficacy in three separate studies representing a total of 3,482 patients. The studies consisted of double-blind, randomized, placebo-controlled dose-ranging studies in patients with Alzheimer’s disease.
Amyloid beta plaque is formed from the breakdown of a larger protein, called amyloid precursor protein. One form, beta-amyloid 42, is thought to be especially toxic. In the Alzheimer’s brain, abnormal levels of this naturally occurring protein clump together to form plaques that collect between neurons and disrupt cell function.
The FDA states that the treatment was clearly shown in all trials “to substantially reduce amyloid beta plaques,” but an FDA advisory panel debated that conclusion.
How Effective Is It?
There is some serious debate within the medical community, Alzheimer’s specialists, and even the FDA itself about how much hope we should put into the new treatment. The FDA took the unusual step of issuing a press release acknowledging the controversy around it.
At issue are the FDA’s decision to fast-track the drug even with less-than-conclusive clinical trial data. The late-stage development program for Aduhelm consisted of two phase 3 clinical trials. One study met the primary endpoint, showing reduction in clinical decline. The second trial did not meet the primary endpoint. Several organizations and think tanks that opposed the approval said that even if it could slow cognitive decline in some patients, the benefit suggested by the evidence would be so slight that it would not outweigh the risk of swelling or bleeding in the brain that the drug caused in the trials.
“With a treatment for a serious, life-threatening disease in the balance, it makes sense that so many people were following the outcome of this review,” the FDA statement read in part. “Further, the data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit. There has been considerable public debate on whether Aduhelm should be approved. As is often the case when it comes to interpreting scientific data, the expert community has offered differing perspectives.”
Nevertheless, weighing the seriousness of Alzheimer’s and the clinical trial results showing a reduction in plaque, the FDA went ahead with its approval, but at the same time required Biogen to conduct further clinical trials.
What are the Risks?
In two clinical trials, about 40 percent of clinical trial patients who got the approved dose of Aduhelm developed painful brain swelling. Symptoms included headache, dizziness, visual disturbances, nausea, and vomiting; about 17 percent to 18 percent of patients had microhemorrhages, or small bleeds in their brain.
The risks with aducanumab involve brain swelling or bleeding experienced by about 40 percent of Phase 3 trial participants receiving the high dose. Most were either asymptomatic or had headaches, dizziness or nausea. But such effects prompted 6 percent of high-dose recipients to discontinue. No Phase 3 participants died from the effects, but one safety trial participant did.
Patients will be monitored for brain swelling before their seventh and 12th infusions. If imaging shows severe swelling, treatment can continue “with caution only after a clinical evaluation and a follow-up MRI demonstrates radiographic stabilization,” according to Biogen.
Similar side effects have occurred in trials of previous amyloid-lowering drugs, but doctors consider them manageable if a patient is evaluated regularly with brain scans. Still, even supporters of approval said that conducting such safety monitoring was more difficult when not done in the carefully controlled regimen of a study.
How Will It Be Administered?
Aduhlem is a monthly intravenous infusion intended to slow cognitive decline in people with mild memory and thinking problems. Importantly, it is intended for those mild cognitive impairment or early-stage Alzheimer’s whose brains contain higher-than-normal levels of amyloid.
Biogen is expecting to launch the drug quickly, possibly in the next two weeks, with more than 600 sites across the country expected to administer it. Clinics for patients with cognitive problems have been scrambling to prepare.
Dr. Jeffrey Burns, director of the University of Kansas Health System’s memory clinic and a site investigator for one trial, told the New York Times that he expected “the phone to be ringing off the hook.” He estimates 25 to 40 percent of the clinic’s roughly 3,000 patients might be eligible.
What Will It Cost?
Biogen said the yearly cost for a maintenance dose of Aduhelm, based on an average patient’s weight, would be $56,000. That’s a list price, not the net price or the price paid by patients with insurance. How much patients will pay out of pocket for the drug will depend on their insurance coverage.
The company said it is committed to helping reduce the costs to those who cannot afford it. Also, much of the cost will land on Medicare since many or most patients will be of Medicare age.