But in a sign of the controversy that has shadowed the drug, an FDA statistical review, contained in the same document, concluded there was conflicting evidence on the drug’s effectiveness because one major study indicated it was effective, while another showed scant benefit. The statistician said a third study should be conducted to clear the matter up.
“The reviewer believes there is no compelling substantial evidence of treatment effect or disease slowing, and that another study is needed to confirm or deny the positive study and the negative study,” the report said.
The agency has said it will decide whether to approve the drug, which is administered intravenously once a month, by early March. It isn’t required to follow the recommendations of outside advisers, but often does.
The medication is designed to treat patients in the earlier stages of disease. If it is ultimately cleared, it would be a major advance — the first drug approved to slow deterioration in brain function, not just to ease symptoms.
There are no treatments to slow or cure Alzheimer’s, a progressive, neurodegenerative disorder that destroys patients’ memories, distorts their personalities and damages their ability to perform everyday tasks. The terminal disease, the most common form of dementia, affects more than 5.8 million people in the United States and places a huge burden on families and caregivers.
The drug, made by the Cambridge, Mass.-based Biogen, is a monoclonal antibody that targets amyloid beta, a protein that can build up in the brain and is implicated in Alzheimer’s disease. The medication was developed from immune cells taken from older people who do not have cognitive problems.
Biogen has estimated about 1.5 million people with earlier-stage Alzheimer’s may be candidates for aducanumab.
The drug’s path has been bumpy and unconventional. After an early trial produced promising data, Biogen launched two large trials to test the drug’s effectiveness. But the company halted the trials in March 2019, after a “futility analysis” by an independent committee indicated the drug did not work.
The failure sent waves of disappointment through the scientific community and prompted some to suggest researchers and drug developers set their sights on targets other than beta amyloid.
But Biogen then took another look at the results, adding more data. The new look suggested that the drug worked — the people in one trial who got the highest dose had a slower cognitive decline. In the other trial, which was still considered a failed study, a subset of participants who got a high dose appeared to do better.
The company had several meetings with the FDA to discuss the data and announced last October that it would apply to the agency for approval.
But some researchers suggest that Biogen’s slicing of the data likely means the drug’s benefits are being exaggerated. And they say they are skeptical that clearing amyloid plaques will be a successful way to treat Alzheimer’s.
The FDA, when considering whether to approve a drug, typically requires “substantial evidence” that a drug is effective — as shown in data from two large, well-controlled clinical trials. But the agency sometimes clears products based on just one large trial and some smaller ones — especially if there is a pressing unmet medical need, as is the case with Alzheimer’s.
The FDA acknowledged in the report released Wednesday that many previous drugs that attempted to target amyloid beta have been failures. But, it added, “there are features of aducanumab’s pharmacologic profile and of the design of its clinical development program that are novel and distinguish it from prior efforts.”
Howard Fillit, executive director and chief science officer of the nonprofit Alzheimer’s Drug Discovery Foundation, said the FDA’s decision will be “really challenging.” He said an approval would be a “major advance” because it is the first drug that has been shown to change the course of the disease.
But he noted the drug’s effect is modest. And he said the data on which any decision will be made is “not the best.”
“Are the data really there, or should there be a third trial to get the best answer?” he said. “The problem is that [such a trial] would take another three to five years, cost hundreds of millions of dollars and, in the meantime, people would not have access to the therapy.”
“I honestly don’t know the right answer,” he said.
If approved, the drug is expected to be a blockbuster, with billions of dollars in sales. There has not been a novel medication approved for Alzheimer’s since 2003. Existing drugs that ease symptoms have effects that are “modest and transitory,” according to the FDA memo. In addition, no treatments are explicitly approved for relatively early-stage patients, it said.
On Friday, the FDA’s outside experts — its Peripheral and Central Nervous System Drugs Advisory Committee — will meet remotely to listen to presentations from the FDA, Biogen and the public, likely including patients and family members affected by the disease.
“Everyone wants to give people hope,” Fillit said. “But the competing and compelling problem is to make sure the FDA makes a sound decision.”