Doctors Blast Biogen Alzheimer Approval as ‘Regulatory Failure’
Doctors Blast Biogen Alzheimer Approval as ‘Regulatory Failure’
(Bloomberg) -- Top researchers who advised the U.S. Food and Drug Administration on Biogen Inc.’s Alzheimer’s drug blasted the agency for approving it, calling the decision a “regulatory failure” that is “at odds with the evidence.”
The New England Journal of Medicine opinion piece, signed by seven members of an advisory panel that opposed clearing Biogen’s Aduhelm, is another sign of persistent furor over the agency’s decision. Two committees of the House of Representatives investigating the approval have asked the Cambridge, Massachusetts-based biotech to turn over documents about the drug’s development and approval.
Doctors and patients are desperate for new treatments for Alzheimer’s disease, which afflicts more than 5 million Americans. While many researchers have backed the FDA’s move, the drug hasn’t been shown to slow cognitive decline, as two big trials sponsored by Biogen yielded contradictory results. Three of the panel members resigned in protest shortly after the FDA approved the drug.
The new commentary is signed by them and four other panel members, including doctors from Harvard Medical School, the Mayo Clinic, and the University of California, San Francisco.
‘Regulatory Failure’
An investigation of Aduhelm’s approval “should be expeditiously performed, so as to learn how this regulatory failure occurred and to ensure that it doesn’t occur again,” the researchers wrote.
Not all the reaction has been negative. Patients, advocates, and groups such as the Alzheimer’s Association have all cheered for the drug. Samit Hirawat, chief medical officer of Bristol Myers Squibb Co., said Wednesday on an earnings call that the approval clarifies FDA’s standard for drugs for neurodegenerative diseases, making it easier to design studies for new therapies.
In early 2019, Biogen halted the two big trials of Aduhelm, also called aducanumab, saying the studies were unlikely to succeed. Later that year, the company said a new analysis of data from the same trials showed the drug might help some patients, and Biogen’s stock soared.
The biotech resumed development, working closely with the FDA’s staff on analyzing the results of one of the trials that provided a glimmer of clinical benefit. Earlier this month, acting FDA Commissioner Janet Woodcock requested an independent review into whether any interactions between Biogen and the agency’s staff were inconsistent with its policies and procedures.
In explaining its approval, the FDA cited Aduhelm’s ability to lower levels of an Alzheimer’s linked protein, called amyloid. That put the agency in the middle of one of the most contentious debates in medicine: whether lowering amyloid levels helps Alzheimer’s patients. In their commentary, the researchers said they were never asked whether the drug’s impact on amyloid was a good indicator of potential benefit.
Pushing Back
Biogen has pushed back against the criticism. Last week, research head Al Sandrock released an open letter denouncing “extensive misinformation and misunderstanding” about the approval that’s taken “a turn outside the boundaries of legitimate scientific deliberation.”
The drug was approved June 7 using a process that allows the FDA to give conditional clearance based on nonclinical data, such as scans or lab results. While accelerated approval is commonly used for cancer drugs, the FDA gave no public sign prior to its decision that it would use it in Alzheimer’s.
Accelerated approval has typically been a way to get promising drugs to the market quickly while definitive studies are underway. Here, the agency gave accelerated authorization to a drug whose big efficacy trials had already been conducted and failed to produce clear results.
“This product failed to meet the evidence bar and the FDA rescued this product using accelerated approval,” commentary co-author Caleb Alexander, an epidemiologist at Johns Hopkins Bloomberg School of Public Health, said in a telephone interview.
Positive View
Over the years, numerous attempts to develop drugs that target amyloid in various ways have failed or been abandoned, the commentary noted. The data “did not support” approving the drug based on its ability to remove amyloid, from the brain, the researchers said in the commentary.
Biogen has said earlier drug candidates weren’t able to clear amyloid from the brain in the same way Aduhelm can, and thus aren’t comparable. A separate editorial written by Gil Rabinovici, a UCSF neurologist, also took the more positive view that the approval is the first step in better understanding of anti-amyloid drugs with potential for improved treatment.
“Whether aducanumab proves to be a blockbuster or a bust, its approval heralds a new era in Alzheimer’s disease care that will feature early, biomarker-supported diagnosis and biologically specific therapies,” he said in the journal article. “The modern age of Alzheimer’s therapy is upon us, and the field may never look back.”
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