U.S. government health officials on Monday approved the first new drug for Alzheimer’s disease in nearly 20 years, disregarding warnings from independent advisers that the much-debated treatment hasn’t been shown to help slow the brain-destroying disease.
The U.S. Food and Drug Administration (FDA) said it approved the drug from Biogen based on results that seemed “reasonably likely” to benefit Alzheimer’s patients.
It’s the only therapy that U.S. regulators have said can likely treat the underlying disease, rather than manage symptoms like anxiety and insomnia.
The decision, which could impact millions of Americans and their families, is certain to spark disagreements among physicians, medical researchers and patient groups. It also has far-reaching implications for the standards used to evaluate experimental therapies, including those that show only incremental benefits.
The new drug, which Biogen developed with Japan’s Eisai Co., did not reverse mental decline, only slowing it in one study. The medication, aducanumab, will be marketed as Aduhelm and is to be given every four weeks via infusion at a doctor’s office or hospital.
Dr. Caleb Alexander, an FDA adviser who recommended against the drug’s approval, said he was “surprised and disappointed” by the decision.
“The FDA gets the respect that it does because it has regulatory standards that are based on firm evidence. In this case, I think they gave the product a pass,” said Alexander, a medical researcher at Johns Hopkins University.
A statement by Dr. Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, acknowledged that “residual uncertainties” surround the drug, but said Aduhelm’s ability to reduce harmful clumps of plaque in the brain is expected to help slow dementia.
“The data supports patients and caregivers having the choice to use this drug,” Cavazzoni told reporters. She said the FDA carefully weighed the input of people living with the deadly disease.
Under terms of the so-called accelerated approval, the FDA is requiring the drugmaker to conduct a followup study to confirm benefits for patients. If the study fails to show effectiveness, the FDA could pull the drug from the market, though it rarely does so.
The company said it aims to complete its followup trial by 2030.
Alzheimer’s a growing concern
Nearly six million people in the U.S. and many more worldwide have Alzheimer’s, which gradually attacks areas of the brain needed for memory, reasoning, communication and basic daily tasks. In the final stages of the disease, those afflicted lose the ability to swallow.
The global burden of the disease, the most common cause of dementia, is only expected to grow as baby boomers continue to age.
Aducanumab (pronounced “add-yoo-CAN-yoo-mab”) helps clear a protein called beta-amyloid from the brain. Other experimental drugs have done that before but made no difference in patients’ ability to think, care for themselves or live independently.
The pharmaceutical industry has been littered for years with failed Alzheimer’s treatments, representing billions in research costs. The FDA’s greenlight is likely to revive investments in previously shelved similar therapies.
Researchers don’t fully understand what causes Alzheimer’s but there’s broad agreement that the brain plaque targeted by aducanumab is just one factor. Evidence suggests family history, education and chronic conditions like diabetes and heart disease may all play a role.
“This is a sign of hope but not the final answer,” said Dr. Richard Hodes, director of the National Institute on Aging, which wasn’t involved in the Biogen studies but funds Alzheimer’s research. “Amyloid is important but not the only contributing factor.”
Biogen said some patients taking aducanumab saw their thinking skills decline 22 per cent more slowly than patients taking a placebo.
But that meant a difference of just 0.39 on an 18-point score of cognitive and functional ability. And it’s unclear how such metrics translate into practical benefits, like greater independence or ability to recall important details.
The FDA’s review of the drug has become a flashpoint in longstanding debates over standards used to evaluate therapies for hard-to-treat conditions.
Groups representing Alzheimer’s patients and their families say any new therapy — even one of small benefit — warrants approval. But many experts have warned that greenlighting the drug could set a dangerous precedent, opening the door to treatments of questionable benefit.
Uncertainty over results
The approval came despite a scathing assessment in November by the FDA’s outside panel of neurological experts. The group voted “no” to a series of questions on whether reanalyzed data from a single study submitted by Biogen showed that the drug was effective.
Biogen halted two studies of the drug in 2019 after disappointing results suggested aducanumab would not meet its goal of slowing mental and functional decline in Alzheimer’s patients.
Several months later, the company reversed course, announcing that a new analysis of one of the studies showed the drug was effective at higher doses and that the FDA had advised that it warranted review. Company scientists said the drug’s initial failure was due to some patients not receiving high enough doses to slow the disease.
But the changes to dosing and the company’s after-the-fact analysis made the results hard to interpret, raising the skepticism of many experts, including those on the FDA panel.
The FDA isn’t required to follow the advice of its outside panellists and has previously disregarded their input when making similarly high-profile drug decisions.
Many questions remain
About 900 U.S. medical facilities are ready to begin prescribing the drug, according to Biogen, with many more expected in coming months.
Many practical questions remain, including: How long do patients benefit? How do physicians determine when to discontinue the drug? Does the drug have any benefit in patients with more advanced dementia?
With FDA approval, aducanumab is certain to be covered by virtually all insurers. Biogen said the drug would cost approximately $56,000 US for a typical year’s worth of treatment and said the price wouldn’t be raised for four years.
Even qualifying for the drug could be expensive as verifying a diagnosis could require brain scans costing $5,000 US or more. Insurers don’t cover the scans because their benefits are unclear, but that could change if the scans become a gateway to treatment.
Additional scans will be needed to monitor potential side-effects. The drug carries a warning about temporary brain swelling that can sometimes cause headaches, confusion and dizziness. Other side effects included allergic reactions, diarrhea and disorientation.