On June 7, the Food and Drug Administration announced that it approved a drug called aducanumab to treat Alzheimer’s disease.
The decision was made using the FDA’s accelerated approval pathway, which requires the company that produces aducanumab, Biogen, to run another clinical trial to clarify whether the drug is beneficial. After that trial, the FDA could rescind its approval.
The drug, which will be sold under the name Aduhelm, took an unusual path through clinical trials. Its trials were halted for several months because it appeared unlikely to have any benefit. But during a second analysis with new data, one of the two trials returned a positive result, Adam Feuerstein and Damian Garde report for STAT News. Normally, FDA approval relies on two clinical trials with positive results, Jon Hamilton reports for NPR.
The FDA’s decision this week contradicts a panel of outside experts who declined to recommend aducanumab for FDA approval in November, reports Laura Sanders for Science News. Supporters of the decision are enthusiastic about the availability of the first new treatment for Alzheimer’s in 18 years, while critics say the data does not show the drug is beneficial and express concern about the precedent this may set for future drug approval.
“This historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease,” says Biogen CEO Michel Vounatsos in a statement, per STAT News. “We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.”
Biogen ran two large clinical trials with aducanumab, called Emerge and Engage, that were both halted in March 2019. Then, in October 2019, Biogen released its new analysis that showed, in the Emerge trial, a high dose of aducanumab delayed cognitive decline in patients by 22 percent over 18 months. The results also showed aducanumab slowed the rate of decline by 0.39 on an 18-point scale used to measure memory, problem-solving and other cognitive functions, report Pam Belluck and Rebecca Robbins for the New York Times.
Aducanumab itself is an antibody that is designed to attach itself to beta-amyloid, a protein in the brain that has been shown to form plaques in people with Alzheimer’s. Critics and supporters agree that aducanumab effectively breaks up beta-amyloid plaques, and the FDA says that effect is enough to qualify aducanumab for accelerated approval.
However, beta-amyloid plaques have not been proven to cause dementia symptoms. As STAT News reports, aducanumab is not a cure for Alzheimer’s, and it does not reverse the progression of the disease. When the outside panel of experts was asked whether the drug effectively treats Alzheimer’s, eight voted “no,” one voted “yes” and two remained uncertain, per Sanders at Science News. The FDA normally follows the recommendations of its advisory panel, but in this case, it did not.
“I’m quite surprised. The most compelling argument for approval was the unmet need but that cannot, or should not, trump regulatory standards,” says Johns Hopkins epidemiologist Caleb Alexander, who served on the expert panel and voted against recommending aducanumab for approval, to STAT News. “It’s hard to find any scientist who thinks the data are persuasive. Unmet need is an important contextual factor but it’s not an evidentiary threshold.”
The clinical trials showed aducanumab has some negative side effects, including brain swelling and bleeding. People who want to use aducanumab will need to undergo brain scans to see if they are eligible for the treatment. Then, the drug requires monthly intravenous infusions that would be given in a doctor’s office or other health care center, per the New York Times. About six million people in the United States have Alzheimer’s, although not all will qualify for treatment with the new drug.
“We have been waiting decades for this,” says Maria Carrillo, a neuroscientist and the chief science officer at the Alzheimer’s Association, to Science News. By delaying the progression of symptoms, she says aducanumab can allow families and patients “to sustain independence, to hold onto memories longer, to be with families longer. That’s important.”