Biogen Hopes Alzheimer’s Drug Mired in Controversy Earns FDA Nod
After scores of failures, regulators are set to rule on aducanumab, which promises to slow dementia.
Jeffrey Borghoff was just 51 when he received a diagnosis of early-stage Alzheimer’s disease. Shortly thereafter, he retired from his job as a software developer and went on disability. He also quickly enrolled in a trial for an experimental Biogen Inc. drug to remove an aberrant amyloid protein from his brain that researchers believe is tied to reduction in memory and brain function in Alzheimer’s patients. Since then, with the exception of a brief interruption, he’s been getting monthly infusions of the medicine, named aducanumab, which he credits with slowing his cognitive decline. Now 57, Borghoff can’t drive because he confuses red and green lights, but he can still cook and take walks with his wife, Kimberly, and their dog. His life, he says, is full.
Now Borghoff is steeling himself: The U.S. Food and Drug Administration is set to rule soon on aducanumab, which has already been rejected by an FDA advisory panel of medical experts. The FDA may also reject the drug, requiring years of additional study. That could eventually force him to search for a trial of a different treatment—something that takes time that many patients simply don’t have.
“We’re fighting like hell to get this drug approved,” says Borghoff, of Forked River, N.J., who also spoke to FDA regulators in favor of the Biogen medicine at a meeting of patients in January. “Every day they are making progress in cancer and diabetes and other diseases. We need something for Alzheimer’s disease,” he says.
The decision, which Biogen says the FDA will make by June 7, is one of the most consequential the agency has faced in years and is guaranteed to be controversial no matter what the outcome. Existing Alzheimer’s drugs only temporarily improve symptoms. If approved, aducanumab could become the first drug ever authorized to slow the course of the most common type of dementia. That suggests the drug could become a hit, providing at least some hope to an estimated 6 million Alzheimer’s sufferers in the U.S.—and likely billions of dollars in annual sales for its makers.
That Biogen’s drug is even up for approval at all is noteworthy. In early 2019, Biogen and its Tokyo-based partner Eisai Co.discontinued two big trials, citing lack of evidence to merit further study. The drug appeared destined to take its place among the hundreds of Alzheimer’s failures over several decades. But Biogen and Eisai, in a surprise move, later reversed course and submitted the drug for approval. “This [FDA review] is a momentous decision of tremendous consequence,” says Marwan Sabbagh, director of translational research at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas and a consultant to Biogen on Alzheimer’s treatments, who thinks the benefit from the drug is meaningful.
Two large trials run by Biogen produced seemingly contradictory results. In one, high doses of the drug slowed patients’ decline by 22% over 18 months. In the second, the drug was ineffective overall. Biogen says some patients didn’t receive high enough doses in the unsuccessful trial. Still, those conflicting results have sharply divided doctors and Alzheimer’s researchers.
“Nobody is ambivalent about this,” says Sabbagh. “They are either for it or against it.”
Some doctors and groups such as the Alzheimer’s Association say the evidence is good enough given the desperate need for a treatment. “The downside of it not working is greatly outweighed by the possibility of being able to give something to people who are dying of Alzheimer’s every day,” says Maria Carrillo, chief science officer for the Alzheimer’s Association. “Waiting another five years for another trial is for us not acceptable.”
Other researchers and physicians say approving a medicine on such uncertain evidence would set a bad precedent. The drug is likely to be expensive, must be infused in a clinic by medical professionals, and is likely to require costly brain scans to monitor for possible side effects such as brain swelling. What’s more, aducanumab’s benefit is modest at best and less than what some doctors consider clinically significant for an individual patient.
Approving the drug now “would send a horrible message to the market for what the FDA is willing to settle for,” says Caleb Alexander, an epidemiologist at Johns Hopkins Bloomberg School of Public Health, who was on the panel of FDA advisors that voted against the drug in November. “It would completely undermine our regulatory system.”
Biogen has a lot riding on the Alzheimer’s treatment, and its share price has swung wildly along with aducanumab’s prospects over the past two years. The drug may cost $30,000 a year, bringing in $5 billion a year in annual sales, estimates Jay Olson, an analyst at Oppenheimer & Co. who gives the medicine only a one-in-three chance of approval. “It is probably the most unusual setup the FDA has ever faced,” he says.
Biogen has said more than 600 clinical sites in the U.S. could begin infusing the drug into patients soon after a potential approval. The drug will also likely require brain scans or spinal taps prior to treatment to confirm amyloid is present. “Our team is currently working to evaluate the capacity at these and other sites to absorb an influx of Alzheimer’s patients,” Biogen Chief Executive Officer Michel Vounatsos said on an April 22 investor call. The company said its executives were unavailable for further comment.
For more than a quarter century, researchers have targeted amyloid, the aberrant protein that clogs the brains of many Alzheimer’s patients. It was first spotted by Alois Alzheimer in 1906, but didn’t become the focus of drug hunters until rare inherited forms of the disease were linked to amyloid buildup in the 1990s.
https://www.bloomberg.com/news/articles/2021-05-13/alzheimer-s-drug-biogen-hopes-controversial-aducanumab-gets-fda-approval