The verdict is in: The FDA has approved Biogen’s controversial Alzheimer’s treatment aducanumab.
The FDA’s approval on Monday is set to cause a ripple effect among drugmakers and researchers studying the elusive disease, the sixth leading cause of death in the U.S., and comes after months of intense controversy over whether Biogen’s Alzheimer’s treatment actually helped with cognitive decline.
For Biogen, the company's all-in bet on aducanumab, now marketed as Aduhelm, comes amid serious troubles elsewhere in its business. Multiple sclerosis drug Tecfidera and spinal muscular atrophy med Spinraza have been facing increasing competitive pressures, leading the company to post a sales decline in 2020.
Aducanumab is a monoclonal antibody designed to break down amyloid plaque buildup that is thought to worsen Alzheimer’s disease. The drug is the first to treat the course of the disease, not just its symptoms, and the first Alzheimer's medicine approval in nearly two decades—and among the few drugs of any kind approved after a stark rejection from the FDA's own advisory panel of experts.
It's a sure win for patients and advocacy groups lobbying for the green light, as well as Biogen and its Japanese pharma partner Eisai, who have urged the drug agency to approve the treatment, arguing that there are no other options to treat the memory-degenerating disease that afflicts more than 6 million people in the U.S.
On the other hand, it’s a stark rebuke against the physicians and the FDA’s own panel of independent advisors who have been sharply critical of the once-failed drug. That group has contended that Biogen’s treatment hasn’t proven effective enough to earn the agency’s coveted approval.
The FDA awarded aducanumab an accelerated approval, which grants an earlier green light to drugs that treat serious conditions and fulfill an unmet medical need.
In its decision on Monday, the FDA said aducanumab “consistently and very convincingly reduced the level of amyloid plaques in the brain” in both studies. A reduction in those plaques is “reasonably likely to predict important benefits to patients,” the agency argued.
Its accelerated approval comes with stipulations. Biogen will have to conduct post-approval studies to verify the treatment’s anticipated clinical benefit. If those trials, known as phase 4 studies, don’t verify aducanumab’s worth, the agency said it could remove it from the market entirely.
The controversy surrounding aducanumab has largely stemmed from results of two conflicting late-stage trials in patients with early-stage and mild Alzheimer’s.
In a trial called Emerge, patients who got the highest dose of aducanumab experienced a 22% improvement on a clinical dementia scale over placebo after 78 weeks, the company said. Yet the same patient group in the Engage study did worse than placebo patients on that same measure, as well as on a test of cognitive function.
None of the members on the FDA’s advisory committee voted in favor of aducanumab in a blistering thumbs-down November vote over whether “strong evidence” showed the antibody slowed cognitive decline in phase 3 studies. A second vote on whether a small phase 1b study showed “supportive evidence” similarly brought in a resounding no vote.
Even with an agency go-ahead in hand, aducanumab is likely to face a number of hurdles before it reaches patients. Physicians may be unsure who should get it and for how long, while payers may balk at its lofty price tag and erect barriers that could limit reimbursement, analysts warn.
Given the “insufficient” evidence supporting aducanumab’s benefits, the drug should cost as little as $2,500, the drug-cost watchdog Institute for Clinical and Economic Review (ICER) said in a draft report (PDF) in May. Even at the $8,300 high end of the threshold, ICER’s estimates are still well below the $50,000 price tag industry watchers have estimated.
For its part, Biogen has said there are more than 600 clinical sites in the U.S. ready to administer the drug following approval with many more in the works. The company said it will set the drug's list price at about $56,000 per year, although executives have previously predicted it will drive “modest revenue” in 2021.
Maria Carrillo, the chief science officer at the Alzheimer’s Association, which has sided with the drug’s approval, said despite concerns, physicians should still “work with people and their families to give them all the information and the options so that people can make informed decisions about whether they want this treatment.”
“We believe people should have that access and ability to decide for themselves today, not four or five years from now when another phase 3 trial can be done,” Carrillo said.
Aducanumab has traveled a long, turbulent journey. Biogen nearly scrapped the drug entirely in March 2019 after it failed a key interim analysis. But in a surprise turnaround just eight months later, Biogen argued that the analysis was “incorrect” because it was based on a smaller data set that featured fewer patients who received high-dose aducanumab. So, the company filed it for approval.
The FDA's aducanumab decision, the most consequential in years, has also been viewed as a tone-setter for drug approvals under the Biden administration and acting Commissioner Janet Woodcock, who is a contender for the permanent slot.
The agency was originally slated to hand its decision over aducanumab in early March. But, in a surprise move against the independent committee’s vote, the agency delayed its PDUFA date by three months while it reviewed additional data from Biogen. The company, however, remained silent over what additional information it handed the agency.
While the delay appeared to be good news for investors, analysts were widely split in their predictions over aducanumab's fate. Some still pegged aducanumab’s chances of making it across the FDA finish line with a clean approval at less than a coin’s flip, although there were thoughts that maybe the drug could warrant a limited approval instead.
The FDA's approval could also be a positive sign for Biogen's rival Eli Lilly, which also has its own up-and-coming Alzheimer’s disease asset donanemab. That drug, like aducanumab, is also a monoclonal antibody targeting amyloid plaques.
Lilly unveiled detailed phase 2 data from a donanemab trial in March that showed it can help Alzheimer’s disease patients by clearing brain plaques, yet questions remain about its safety and clinical significance.
Editor's note: This is a developing story and it will be updated throughout the day.