(Bloomberg) — Biogen Inc.’s experimental Alzheimer’s disease therapy failed to gain support from a panel of U.S. Food and Drug Administration advisers on Friday, putting the drug at a crossroads as the agency weighs approval.
The outside experts voted 8 to 1, with 2 undecided, that data from a single clinical trial with positive results was insufficient to show Biogen’s drug works. They also voted 10 to 0, with 1 undecided, that the positive study shouldn’t be considered primary proof the drug works in light of conflicting evidence from a different trial.
The votes contradict a report FDA reviewers prepared ahead of the meeting that supported the efficacy of the drug, called aducanumab, though there was dissent in the agency. The FDA will continue the review process with a decision by March 7, 2021.
Advisers said the trial they were asked to assess wasn’t finished and even though the data appeared positive, they couldn’t know for sure.
“There’s a huge danger in approving something that is not effective,” said Joel Perlmutter, a panel member and neurology professor at Washington University School of Medicine in St. Louis, Missouri.
Approval of Biogen’s therapy would be a milestone for the long battle against Alzheimer’s, a harrowing brain-wasting disease that affects some 5.8 million Americans. While there are other drugs that temporarily improve some symptoms, none slow or stop the eventually lethal destruction of brain neurons, the Alzheimer’s Association said in a report last year.
Aducanumab has also become a singularly important drug for Biogen, which has seen its market value fluctuate substantially over the past two years as it halted study on the drug, restarted its research, and then submitted it to regulators for approval earlier this year.
Shares of Biogen were halted throughout the regular trading day on Friday. On Wednesday, the stock surged 44% after the upbeat assessment from the FDA staff, though some of those gains were given back Thursday, when Biogen slid 7.5%.
“We will continue to work with the FDA as it completes its review of our application,” Michel Vounatsos, chief executive officer at Biogen, said in a statement.
The advisory committee’s recommendations aren’t binding. The FDA often calls on panels of experts, including researchers, medical professionals and patient representatives, when it is considering whether to approve a new drug. Wall Street analysts said the FDA seemed set on viewing the drug positively.
“This will be a test for the FDA on what happens when the FDA is on one extreme and the panel is seemingly on the other, with science and evidence or the lack thereof being at the core of discussion,” Mizuho analyst Salim Syed said in an email to Bloomberg News.
Aducanumab targets amyloid plaque that builds up in the brains of Alzheimer’s patients, though scientists don’t know what role it plays in the disease. Brain scans showed the drug removed the plaque, but whether that had any benefit is unclear.
The FDA hasn’t followed the typical process for advisory panels this time, starting with posting a joint report with Biogen on aducanumab’s clinical trial data ahead of the meeting. Usually, the FDA posts its own report outlining staff’s review of the data.
The agency declined to answer questions on why it combined the report and whether Biogen was able to review it prior to it being made public. The agency also gave panel members the option to vote undecided when typically it asks for yes or no answers.
The therapy has had a tumultuous path to FDA consideration. Biogen halted its study of the drug in March 2019 on signs it wouldn’t work, then revived it in October that year after it said a review of data in one of two trials showed it was successful.
Biogen, based in Cambridge, Massachusetts, presented data from the two aducanumab trials at a conference in December. One trial showed the drug may slow the progression of the disease, while the other found no effect. Researchers questioned the positive results because not all participants completed the trials.
Kyle Krudys, a clinical analyst at the FDA, told the advisory panel in a recorded presentation that the trial results that showed no effect of the drug on patients shouldn’t detract from the positive trial. “I have concluded that the applicant has provided substantial evidence of effectiveness to support approval,” Krudys said.
Meanwhile, Tristan Massie, a statistical reviewer at the FDA, determined a third clinical trial followed through to completion is necessary to determine whether aducanumab works.
“Excluding data from a large trial without sufficient justification is unscientific, statistically inappropriate and misleading,” Massie said in a prepared presentation for the advisers.
Billy Dunn, the director of FDA’s Office of Neuroscience in the Office of New Drugs, summed up the agency’s view on the drug in a positive light at the beginning of the meeting without a nod to Massie’s concerns. He focused on Alzheimer’s ranking as the sixth leading cause of death among Americans, according to the Centers for Disease Control and Prevention.
“We are highly sensitive to the need for new drugs for Alzheimer’s disease,” Dunn said.
G. Caleb Alexander, a panel member and epidemiologist at Johns Hopkins Bloomberg School of Public Health, called the FDA’s materials “strikingly incongruent” and said Massie’s statistical review was “well done.”
“It just feels like the audio and video on the TV are out of sync,” Alexander said.
If aducanumab is cleared, sales are expected to total about $4.7 billion in 2025, according to data compiled by Bloomberg. Biogen developed the therapy with the Japanese drugmaker Eisai Co.
Indianapolis-based Eli Lilly & Co.has several experimental Alzheimer’s drugs in development and shares of the company fell as much as 4.4% after the panel vote. Like Biogen’s drug, Lilly’s donanemab aims clear amyloid plaque from the brain.
(Adds FDA’s decision date in third paragraph, CEO comment in ninth paragraph)
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