The Food and Drug Administration on Monday approved the drug aducanumab as a treatment for Alzheimer’s disease, the first ever intended to slow the progression of the incurable dementia. The go-ahead marks a rare case in which the FDA went against the recommendations of the outside panel it solicited for advice, who did not endorse approval based on mixed evidence of the drug’s effectiveness. However, some experts and many patients’ families are likely to embrace the drug.
Aducanumab is an antibody treatment designed to target misfolded clumps of amyloid beta, a protein that’s thought to play a crucial role in causing the steady destruction of the brain in patients with Alzheimer’s disease. It was originally discovered by Swiss company Neuroimmune and licensed for development by the Massachusetts company Biogen, with the first clinical trials beginning in 2012. The FDA’s decision came Monday morning, the last day of an already extended deadline to review Biogen’s petition for approval. The injectable drug is the first approved to treat Alzheimer’s in nearly 20 years, and the first in its class; it will now be sold under the brand name Aduhelm.
“Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s. As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation,” said Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, in a statement.
Though aducanumab had shown plenty of promise in early trials, data from the two Phase III trials used to secure its approval would eventually cause a serious divide among experts. In early 2019, Biogen suspended its research on the drug, after a review committee determined that the drug would not meet its goals of noticeably slowing down cognitive impairment in people with early Alzheimer’s. However, by October, the company changed course, now arguing that at least one trial’s updated data did show a statistically significant effect, while the second had suggested that the drug would work when taken at higher doses.
But many scientists have remained skeptical of Biogen’s arguments and the data. In November 2020, an advisory committee assembled by the FDA to review the clinical trial data largely ruled against approval, with 10 of 11 votes agreeing that the data did not show “primary evidence of effectiveness” in treating the neurological disease. Since then, other scientists and doctors have continued to argue against approval, with some going as far to say that they wouldn’t prescribe the drug to their patients if available; others have argued that the drug’s likely marginal benefits will not be enough to justify the expected costs of $50,000 a year and possible serious health risks, such as brain bleeding.
At least some patient advocates and relevant organizations, such as the Alzheimer’s Association, are supportive of the drug’s approval, though, stating that even a small benefit is worthwhile to patients and their families and that it may spur new innovation in the field of Alzheimer’s disease research, which has historically led to few breakthroughs.
“This FDA drug approval ushers in a new era in Alzheimer’s treatment and research. History has shown us that approvals of the first drug in a new category invigorates the field, increases investments in new treatments and encourages greater innovation. We are hopeful and this is the beginning—both for this drug and for better treatments for Alzheimer’s,” said Maria Carrillo, chief science officer of the Alzheimer’s Association, in a statement to Gizmodo.
This may not be the final word on aducanumab. The drug is being approved under a special system known as accelerated approval, first created in 1992. According to the FDA, this is used to “allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint.”
In an FDA press conference held Monday afternoon, Cavazzoni and Peter Stein, director for the Office of New Drugs, stated frankly that the current evidence for aducanumab did not merit a traditional approval that would endorse the drug’s effectiveness in treating Alzheimer’s disease. In choosing to approve the drug through an accelerated process, based on data showing that it does break down amyloid in the brain, the FDA argues that it’s “reasonably likely” to believe that the data will eventually show a clear clinical benefit in slowing cognitive decline.
In exchange for this speed, Biogen will be required to fund a new randomized, controlled clinical trial of the drug, and if it fails to perform this research or if the data fails to show a benefit there, the FDA may then decide to pull the drug from the market. Some experts have argued, however, that aducanumab’s approval may still harm or delay research into new Alzheimer’s treatments if it does turn out to be ineffective.
Time will tell if any of these fears or hopes turn out to be true.
This article has been updated with comments from the FDA during its press conference on the drug’s approval this afternoon.