But in an explicit acknowledgment of the uncertainties about the effectiveness of the drug, the FDA did not grant the medication full approval. Instead, the agency cleared the drug — its brand name will be Aduhelm — based on its ability to reduce clumps of amyloid beta in the brain, a hallmark of the disease. It ordered the drug’s maker, the biotech giant Biogen, to conduct a post-approval study confirming the medicine actually slows cognitive deterioration. If the medication does not provide such a clinical benefit, the FDA’s approval could be withdrawn.
Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, said officials believe it is “reasonably likely” that the reduction in amyloid clumps will confer “important benefits to patients.”
Monday’s FDA decision was the most contentious in years and followed prolonged debate among researchers, doctors, patients and advocates about whether the medication works — a consequence of the drug’s complicated history. One of the biggest points of disagreement is whether a reduction in amyloid beta, a sticky compound that many scientists believe damages communication between brain cells and eventually kills them, results in a slowdown in cognitive decline.
Advocacy groups and patients praised the FDA decision, citing the paucity of drugs to help patients and saying the approval would stimulate newfound interest and investment in researching therapies for the progressive, terminal illness and give patients valuable time to be with their families and perform everyday tasks.
The decision “is a victory for people living with Alzheimer’s and their families,” said Harry Johns, president and chief executive of the Alzheimer’s Association.
Jeff Borghoff, 57, who was diagnosed with early-stage Alzheimer’s five years ago and has received aducanumab in clinical trials, expressed elation about the FDA decision.
“This is epic news,” said Borghoff, a resident of Forked River, N.J., who credits the drug with keeping his condition stable. “Now, I may have time to watch my kids get married. My wife said, ‘I have more time with you now.’ ”
But critics assailed the decision, arguing that data on the drug’s effectiveness is weak and that the FDA approval represents a dangerous lowering of standards in response to pressure from patients and advocacy groups.
“I’m surprised and disappointed,” said G. Caleb Alexander, an internist and epidemiologist at the Johns Hopkins Bloomberg School of Public Health and a member of the FDA advisory committee that last fall resoundingly rejected the drug.
“I think this product was driven across the line by the magnitude of unmet need, which is enormous,” he said. “But unmet needs can’t trump regulatory standards, and my concern is that in this instance they may have.”
Alexander also noted other amyloid-reducing drugs have not been shown to improve cognition — a point disputed by FDA officials, who said an internal agency study indicated that eliminating amyloid clumps could be helpful to patients.
Public Citizen, a watchdog group and frequent critic of the FDA, said in a statement Monday that the agency’s close collaboration with Biogen before and after the company’s application seeking approval “dangerously compromised the integrity of the agency’s review.”
The FDA’s Cavazzoni said she was satisfied the interaction between the staff and the company “was appropriate and necessary,” given the FDA’s questions and the complexity of Biogen’s application.
The intravenous treatment does not cure Alzheimer’s disease or reverse it. On Monday, Biogen said it would charge $56,000 a year per patient, making it a blockbuster product for the company and adding billions of dollars to the nation’s health tab. Its stock rose 38 percent.
A Boston group that assesses the value of treatments — the Institute for Clinical and Economic Review — said this year that aducanumab, to be cost effective, should be priced at $2,500 to $8,000 a year per patient.
Medicare is likely to shoulder much of the cost of the drug, given the age of people with Alzheimer’s, but it has not indicated its plans for coverage. Private payers will be under intense pressure to pay for the treatment but may push back on the price. It’s not clear yet how much patients on government or private insurance will have to pay in cost-sharing.
The medication is a monoclonal antibody, a protein made in the laboratory that can bind to substances — in this case, clumps of amyloid beta. It is designed to trigger an immune response that reduces the plaques.
About 6.2 million Americans have Alzheimer’s, a number projected to more than double by 2050, barring breakthroughs in treatment, according to the Alzheimer’s Association.
The drug was tested in people with the earliest stages of disease — those with mild cognitive impairment or early-stage dementia who had undergone testing to confirm the presence of amyloid clumps in their brains. Several doctors said Monday they were preparing to offer the drug to their patients and would focus on that population in using the drug. Biogen said Monday that up to 2 million people in the United States might be eligible for the treatment.
The FDA did not restrict which patient groups could get the drug. Peter Stein, director of the Office of New Drugs at the agency, said in an interview that there was “no particular reason” why the reduction of amyloid clumps would benefit patients at one stage of the disease and not others. He said physicians should discuss the medication with their patients and decide on the best course.
Ronald C. Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center, called the FDA’s conditional approval “a good outcome to a complicated situation.” He said the decision means patients will be able to receive the treatment outside of clinical trials, but because of the “equivocal nature” of the efficacy data, the company will have to conduct another trial proving the therapy works.
If the FDA had required such a trial before granting approval, he said, the drug would not have been available to patients outside of studies for another three to five years, an outcome he viewed as undesirable. He also predicted Aduhelm will be just one element in an anti-Alzheimer’s arsenal in coming years, as researchers develop combinations that are more effective than single medications.
Jason Karlawish, a neurologist at the University of Pennsylvania’s Perelman School of Medicine, had a starkly different view. He wrote in a May 30 column for Stat, a news site that covers medicine and health, that he would not prescribe aducanumab if approved, because the data were incomplete and the therapy had not been properly studied.
On Monday, after the FDA announcement, he expressed continued reservations about the drug but said he would discuss it with his patients and respect their choices. But he said some patients and colleagues had expressed discomfort about the FDA’s decision, saying evidence of lowering amyloid and improving cognition was thin. Karlawish also said he was concerned it would be difficult to conduct the follow-up study on the drug once it is widely available outside of clinical trials.
The FDA has used its accelerated approval program many times for cancer drugs, clearing therapies, for example, that shrink tumors and then requiring a follow-up study showing whether the drug improves survival. But getting pharmaceutical companies to comply with mandates to conduct the post-approval studies has at times been difficult, and the agency has sometimes been slow to yank approved drugs from the market, even when the follow-up studies fail or aren’t completed.
The drug has followed a rocky road. In 2019, Biogen halted two late-stage trials halfway through after an assessment concluded the studies would not reach their goals of slowing cognitive and functional impairment in Alzheimer’s patients. But in a sharp reversal, a company analysis with additional data released several months later came to a different conclusion.
In one of the clinical trials, that analysis found, people given the drug declined 22 percent more slowly than those who received a placebo. The other trial failed to reach its goal, though the company was encouraged by data from a subset of study participants who got more of the drug. Biogen concluded a key to effectiveness was giving patients a high enough dose for a long enough time.
Critics, however, said the data had been selected to make the drug look better than it was. In an acrimonious meeting last fall, an FDA advisory committee recommended against the drug’s approval and harshly rebuked the agency’s review staff for supporting the medication so strongly and working closely with the company.
But supporters of the drug Monday were ecstatic about what they called a watershed moment following years of crushing disappointments in trying to find a way to treat the devastating disease.
Michel Vounatsos, chief executive at Biogen, called the decision a “historic moment” that would “transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.”
The approval bolsters the long-debated theory proposed in the early 1990s that targeting amyloid plaques can be an effective way to treat Alzheimer’s. Detractors have complained that the focus on amyloid has squeezed out work on other important approaches, such as targeting a protein called tau or examining the role of inflammation.
Supporters counter that while multiple approaches should be pursued, the aducanumab approval shows that anti-amyloid treatments can be beneficial.
Aduhelm can sometimes cause side effects, the FDA said, including temporary swelling of the brain that usually does not cause symptoms, though some people may have headaches, confusion or dizziness. Other potential complications are tiny spots of bleeding in the brain and disorientation.
Biogen has said it has 600 sites throughout the country ready to administer the drug.