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The Food and Drug Administration has approved Biogen’s Alzheimer’s disease treatment, ushering in the first new drug for the disease in nearly two decades.
The drug, which was previously known as aducanumab but will be sold under the brand name Aduhelm, is designed to erode the sticky plaque that builds up in the brains of Alzheimer’s patients. Scientists theorize the substance kills brain cells and causes the memory loss characteristic to the disease.
An advisory committee voted in November that Biogen’s tests failed to show the drug effectively treats Alzheimer’s. The FDA generally follows the advice of advisory committees, but has occasionally decided differently.
The FDA approved the drug under a special accelerated pathway, which allows for the use of drugs that are reasonably likely to have a benefit for patients, even when there is uncertainty about how well they work.
“There has been considerable public debate on whether Aduhelm should be approved. As is often the case when it comes to interpreting scientific data, the expert community has offered differing perspectives,” Dr. Patrizia Cavazzoni, the director of the FDA Center for Drug Evaluation and Research, said in a statement on Monday. “The Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy.”
Close to 6 million Americans have Alzheimer’s, making treating the disease a potential blockbuster revenue opportunity for drug companies. Biogen invested more than $2 billion in developing aducanumab and other experimental Alzheimer’s drugs.
Aducanumab’s rocky road to the FDA almost ended in failure 2 years ago
Biogen’s FDA application hinged on two identical late-stage clinical trials that were shut down in early 2019 after an interim analysis indicated they would likely fail.
But Biogen didn’t cut its losses. The company continued to parse through the data. Roughly six months later, Biogen surprised the drug industry by announcing that a subset of patients in one of the trials was showing positive signs. The participants’ amyloid plaque levels were down and their ability to recall words, remember life events, prepare meals, and complete other small, everyday aspects of life improved.
Those test results made up the bedrock of Biogen’s FDA application, but data from the other failed late-stage trial and another early stage trial were also included. The separate outcomes of the late-stage, or Phase 3, tests were a point of contention during the FDA’s review of the drug.
Neurologist David Knopman, who was involved in Biogen’s clinical trials, called on the biotech firm last year to run a new late-stage trial of the drug, stating that the data Biogen had presented didn’t prove the drug helped patients.
“Perfection may be the enemy of the good, but for aducanumab, the evidence doesn’t even rise to ‘good.’ Contrary to the hope that aducanumab will help Alzheimer patients, the evidence shows it will offer improvement to none, it will harm some of those exposed, and it will consume enormous resources,” he wrote to the FDA in October.
The advisory committee included researchers, clinicians, and a biostatistician. It largely said that Biogen’s argument in favor of approval was full of holes. But FDA officials found the data from the successful Phase 3 trial “robust and exceptionally persuasive” and determined that the positive trial results could be used to back up Biogen’s application.
Biogen spent $2 billion developing its Alzheimer’s drugs over the last five years
RBC Capital Markets analyst Brian Abrahams estimated in January that Biogen had a 15% chance of approval ahead of the the FDA’s decision. Others placed Biogen’s odds of approval closer to 40% or 60%, citing cases in which the FDA has approved products for previously untreatable diseases.
Those odds looked even better after the FDA delayed its decision deadline from March 7 to June 7. Deadline extensions commonly end up with a drug being approved, analysts said in January.
Patient advocacy groups also supported approval, citing the lack of options for patients. The last entirely new drug for Alzheimer’s, Namenda, was approved in 2003 for people with moderate to severe forms of the disease. The other drugs to hit the market since have been combinations of new and existing products.
The Alzheimer’s field has been filled with trial failures, leading several large pharmaceutical companies to shut down their work in the area.
Biogen has spent at least $2 billion developing three potential treatments over last five years, according to financial statements. One of those drugs was shelved in 2019 due to poor trial results, while another, BAN2401, is still being tested by partner Eisai Inc.
In the meantime, Biogen’s strategy of targeting the sticky amyloid plaque has been abraded by drug failure after drug failure from other companies. The theory got some support in January when Eli Lilly and Company reported success with an amyloid-targeting drug in a Phase 2 study.
But most drug companies still working in Alzheimer’s have left the amyloid argument behind, instead targeting other neurological elements in the hopes of treating the disease.