FDA on Monday issued its first approval for a new Alzheimer's treatment in nearly two decades, giving a conditional green light to aducanumab, a Biogen drug that attacks the beta-amyloid proteins associated with Alzheimer's disease. But the approval comes amid significant controversy over whether the drug—which will be released under its brand name, Aduhelm—is actually effective.
Details on Aduhelm's approval process
Biogen launched two Phase 3 randomized controlled clinical trials on Aduhelm—but the trials were halted in March 2019, after independent monitors determined the drug was unlikely to benefit patients.
However, in October 2019, Biogen announced that it had conducted a new analysis of data from the trials. According to the updated analysis, a high dose of Aduhelm in one trial showed a small benefit in slowing cognitive decline, and in both trials Aduhelm was effective at removing beta-amyloid proteins.
The analysis also revealed significant side effects. Around 40% of participants receiving the higher dosage of Aduhelm developed brain swelling or bleeding, and around 6% of high-dose participants stopped taking the drug due to side effects. Further, one person died in an earlier safety trial after an adverse reaction.
Biogen submitted its analysis of the Phase 3 trials to seek FDA approval for the drug. Late last year, a panel of independent experts convened by FDA looked at Biogen's data. They determined there was not enough evidence to suggest the treatment had a significant benefit for patients, and they argued the drug should not be approved.
However, FDA is not obliged to follow the panel's recommendations, and on Monday it decided to approve Aduhelm on a conditional basis—saying Biogen must conduct a large clinical trial in order to confirm that removing beta-amyloid proteins actually leads to cognitive benefits for patients.
If that trial fails, FDA could rescind the drug's approval.
"The data included in the applicant's submission [was] highly complex and left residual uncertainties regarding clinical benefit," Patrizia Cavazzoni, director of FDA's Center for Drug Evaluation and Research, wrote on FDA's website.
Regardless, FDA decided to approve the drug through accelerated approval, a process designed "to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit," according to FDA.
Biogen did not disclose how much Aduhelm, which will be administered as a monthly infusion, will cost. However, analysts expect it will be priced between $10,000 and $25,000 per year, STAT News reports. Although the drug was tested on only early-stage Alzheimer's patients confirmed to have beta-amyloid in their brains via PET scans, FDA's label for the drug does not impose similar restrictions; rather, the label says the drug is "for the treatment of Alzheimer's disease."
Experts were divided on FDA's approval. Ronald Petersen, a neurologist who leads the Mayo Clinic Alzheimer's Disease Research Center, said he's "hopeful" for patients who qualify for the drug.
"Now we have a potential treatment for them that may modify the underlying disease course," he said. "But the largest responsibility for us is to educate patients and physicians as to what this means. This is not going to be penicillin for Alzheimer's disease."
However, some experts expressed concern about the approval, saying that—while it's clear Aduhelm reduces levels of beta-amyloid proteins—there's little evidence that it leads to an improvement in cognitive function.
G. Caleb Alexander, a member of FDA's advisory committee and an internist, epidemiologist, and drug safety and effectiveness expert at the Johns Hopkins Bloomberg School of Public Health, said prior to FDA's decision that an approval would "set a remarkably dangerous precedent—not only for the field of Alzheimer's research but also for the broader regulation of prescription drugs in our country" (Feuerstein/Garde, STAT News, 6/7; Belluck/Robbins, New York Times, 6/7; Belluck/Robbins, New York Times, 6/5; Herman, Axios, 6/7).