The Food and Drug Administration approved an Alzheimer's drug on Monday, the first time the agency has approved a new therapy for the disease since 2003. The moves comes after an independent advisory panel urged the agency in November to reject the drug, called aducanumab, warning that the treatment hadn't been shown to help slow the progression of the disease.
Aducanumab is the only drug that U.S. regulators have said can likely treat the underlying disease, rather than manage symptoms such as anxiety and insomnia. It's made by the Massachusetts-based company Biogen and will be sold under the name Aduhelm.
The decision, which could affect millions of older Americans and their families, is certain to spur 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.
Maria Carrillo, chief scientific officer for the Alzheimer's Association, hailed the approval as "a historic moment for our field."
"The Alzheimer's Association believes that approval ushers a new era in Alzheimer's treatment and even in research," she said. "For people living with Alzheimer's, this treatment means a potential to delay decline."
The FDA acknowledged the controversy surrounding the drug in a statement from Dr. Patrizia Cavazzoni, director of the FDA's Center for Drug Evaluation and Research.
"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," she wrote, adding that the "data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit."
During a media briefing Monday, Cavazzoni explained that the drug had been approved through the FDA's accelerated approval pathway, an approach which allows the FDA to approve drugs for serious or life-threatening illnesses when the drug has "been shown to show improvement on a surrogate endpoint that is considered to be reasonably likely to predict clinical benefit."
In the case of Aduhelm, the surrogate endpoint was reduction of amyloid plaque in the brain, clumps of protein that are considered a hallmark of the disease. Reduction of these plaques "is reasonably likely to predict clinical benefit of the drug," she said.
But saying a drug is reasonably likely to predict clinical benefit does not mean it is guaranteed to do so. Because of this, drugs approved through the FDA's accelerated pathway must continue to study the drug to confirm its clinical benefits.
"If the clinical benefit is not confirmed, or if the study is not conducted in a timely manner, we may withdraw this therapy's approval," Cavazzoni said.
Benefits must be confirmed
Dr. Jason Karlawish, co-director of the Penn Memory Center in Philadelphia and a site investigator for Biogen's clinical trials of the drug, disagreed with the FDA's decision.
"It's going to present a real challenge for patients and caregivers and clinicians about whether to prescribe the drug," he said. “It's going to also present challenges for researchers who are conducting trials and are planning trials to develop better drugs."
Still, Karlawish said he would prescribe aducanumab, but only "after having had a conversation with the patient and family members about the notable uncertainties that surround whether the drug even works."
The new drug, which Biogen developed with Japan’s Eisai Co., did not reverse mental decline, only slowing it in one study.
The FDA is requiring the drug maker to conduct a follow-up study to confirm the drug’s benefits for patients. If the study fails to show effectiveness, the FDA could pull the drug from the market, though the agency rarely does so.
The drug will cost $56,000 a year, according to Biogen. The drug is given as an infusion every four weeks at a cost of $4,312 per infusion, based on the average weight of a patient with mild cognitive impairment or mild dementia.
A preliminary analysis by one group found that the drug would need to be priced $2,500 to $8,300 per year to be a good value based on the “small overall health gains” suggested by company studies. The nonprofit Institute for Clinical and Economic Review added that “any price is too high” if the drug’s benefit isn’t confirmed in follow-up studies.
Nearly 6 million people in the U.S. and many more worldwide have Alzheimer’s disease, 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 millions more Baby Boomers progress further into their 60s and 70s.
Aducanumab (pronounced “add-yoo-CAN-yoo-mab”) aims to help clear harmful clumps of a protein called beta-amyloid from the brain. Other experimental drugs have done that before but they made no difference in patients’ ability to think, care for themselves or live independently.
The pharmaceutical industry’s drug pipeline has been littered for years with failed Alzheimer’s treatments, representing billions in research costs. The FDA’s green light is likely to revive investments in similar therapies previously shelved by drugmakers.
The new medicine is made from living cells that will have to be given via infusion at a doctor’s office or hospital. The most common side effects were inflammation in the brain, but most cases did not cause symptoms or lasting problems.
The FDA’s review of the drug has become a flashpoint in long-standing debates over standards used to evaluate therapies for hard-to-treat conditions. On one side, 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.
The approval came despite the 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.
Cambridge, Massachusetts-based 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.