Medical experts, regulators, industry, and deficit hawks continue to clash over the FDA’s decision to grant accelerated approval to Biogen Inc.’s Alzheimer's treatment Aduhelm (aducanumab), prompting renewed interest in this class of drugs.
For nearly two decades, those affected by Alzheimer’s have been frustrated by a dearth of new treatment options. Until now, available treatments have exclusively offered symptom relief as opposed to options for slowing, stopping, or reversing the progression of the disease.
The FDA’s decision early last month to grant accelerated approval of Aduhelm has spurred new hope
for the 6.2 million Americans living with Alzheimer’s dementia, and their loved ones.
"The Alzheimer's Association believes that approval ushers a new era in Alzheimer's treatment and even in research," said Maria Carrillo, chief scientific officer for the Alzheimer's Association in a statement. "For people living with Alzheimer's, this treatment means a potential to delay decline."
The decision also appears to have prompted Eli Lilly to announce that it will be seeking approval following a trial involving 272 patients with Alzheimer's for its similarly acting drug donanemab, which has been given “breakthrough” status by the FDA.
But critics have accused the FDA and proponents of this drug of promoting false hope in a treatment that presents significant medical risks but small to no clinical benefits.
The FDA’s decision went against the recommendation of its expert advisory panel that was convened to weigh in on the merits of the drug’s approval. Out of the ten experts who served on the panel, eight voted against approval and two were undecided.
Aaron Kesselheim, professor of medicine at Harvard Medical School, has served on the FDA’s expert advisory panel since 2015, and is one of three of the panel’s members who have resigned in the aftermath of this decision.
“It is clear to me that FDA is not presently capable of adequately integrating the committee’s scientific recommendations into its approval decisions,” he wrote in his resignation to acting FDA Commissioner Janet Woodcock, calling it “probably the worst drug approval decision in recent U.S. history”.
This class of drugs is intended to work by reducing clumps of a protein called amyloid plaque that has been found to develop in the brains of patients with Alzheimer’s, under the theory that a reduction in amyloid plaque will stall or slow progression of cognitive decline.
Like other drugs that have been developed for this purpose, the Aduhelm trials thus far failed to sufficiently demonstrate such cognitive improvement.
But in an interview with Bio Century, commissioner Woodcock defended the decision
explaining that despite insufficient data on clinical benefits to the patient there is solid evidence that the drug causes significant reductions of amyloid plaque in the brain which, as yet unproven, is sufficiently likely to result in a clinical benefit, making the drug “a very solid accelerated approval”.
Accelerated approval is a status the FDA can assign to drugs that “fill an unmet medical need” even though sufficient evidence of a clinical benefit is lacking based on findings of a surrogate endpoint, i.e., in this instance, amyloid plaque reduction.
Drugs identified for accelerated approval are then required to undergo a stage four trial in order to provide confirmation of a clinical benefit. If the trial fails to sufficiently confirm the necessary clinical findings, the FDA may revoke its approval.
Patrick Hope, Executive Director of the Medical Imaging and Technology Alliance (MITA), also hailed the decision. “The action taken today by the FDA will give patients and caregivers access to the first-ever Alzheimer’s disease-modifying treatment," he said in a statement. "Now, the Centers for Medicare & Medicaid Services (CMS) needs to act to update its outdated coverage and payment policies and provide patients with access to amyloid PET diagnostic drugs.”
According to Biogen, the maintenance dose per patient of Aduhelm is expected to cost $56,000 a year. Further, in order to monitor the effects of treatment and the occurrence of bleeding in the brain and other known dangerous side effects, patients taking Aduhelm require frequent brain monitoring with PET imaging.
CMS has the final say as to what extent Medicare coverage will be afforded for this treatment, but due to the lack of limitations prescribed by the FDA and intense industry lobbying, many fear that if decided incorrectly
, the overall cost of this course of treatment will place an unmanageable financial strain on insurance companies and the Medicare system.