The evolution of medicine over the past few centuries — from primitive practices like bloodletting to the adoption of evidence-based therapies — is nothing short of breathtaking. And yet, when it comes to a disease particularly close to my heart, Alzheimer's, cures remain elusive. Though there are effective drugs out there, they primarily seek to treat symptoms of Alzheimer's rather than the disease itself.
My first experience with an Alzheimer’s patient occurred in a neurology clinic I worked in during my last year of college. Mr. X was an older man, accompanied by his beloved wife of 30 years. He was prescribed donepezil, but it didn’t seem to be working — in the exam room, he struggled to recognize where he was, leading the medical assistant to grow flustered. When the physician finally entered, Mr. X’s wife pleaded with them to prescribe her husband something more effective. The rest of the conversation remains a blur to me, but I left the clinic with a newfound fear of Alzheimer's and what it does to a person’s mental capacities.
Recently, the FDA approved the Alzheimer’s drug Aducanumab, which purported to be the first to actually treat the underlying cause of the disease. A monoclonal antibody capable of removing a hallmark feature of Alzheimer’s, beta-amyloid plaques, Aducanumab gave many in the scientific community hope that it would stop the disease in its tracks. The drug’s manufacturer, Biogen, worked quickly to push it through clinical trials — but unfortunately, Aducanumab was not the silver bullet clinicians and patients were hoping for. It failed, just as other alpha-beta plaque targeted medications had in the past. As a result, Biogen ended clinical trials early, and participants were abruptly informed of the failure.
And yet, the FDA still approved Aducanumab. As a medical student, I watched from the sidelines as the agency implemented an "accelerated approval process" to authorize Aducanumab’s use — an approval based solely on the drug’s ability to eliminate the aforementioned alpha-beta plaques. This would make sense, of course, if the evidence bore out that these alpha-beta plaques directly lead to cognitive decline. However, it doesn’t: More than 25 different clinical trials failed after drugs successfully targeted beta-amyloid plaques but did not result in cognitive benefits. This means, alarmingly, that Aducanumab was approved without the rigorous evidence and checks and balances that are the foundation of the scientific process.
For me, the scariest part of the FDA’s circumvention of the integral protective yellow tape of medicine was that Aducanumab has potentially lethal side effects, including cerebral edema and microhemorrhage. As a result, patients are required to undergo MRIs in order to receive the drug. This strikes me as a direct contradiction of the first Hippocratic tenet of nonmaleficence, "First, do no harm." As a med student, I feel that by recommending a drug with unknown benefits (or possibly nonexisting benefits) and known deleterious and even deadly side effects, the FDA has put all prescribing clinicians at risk of violating our own Hippocratic oaths.
And yet, there is hope: In the last two months, the medical community has fought back against the FDA approval of Aducanumab. We’ve forced a label change, and the drug's label has been narrowed to patients with mild cognitive decline. In addition, three vocal FDA advisory members have resigned; one member, Dr. Aaron Kesselheim, even went so far as to state, "This might be the worst approval decision that the FDA has made." The medical community has also applied pressure to the acting FDA Commissioner, Janet Woodcock, who has since called for an independent investigation into Aducanumab's approval process.
In addition, numerous hospital chains and medical institutions, including UNC Medicine, have posted informational webpages clearly laying out the drug's dubious efficacy and dangerous side effects. Other major hospitals, including Cleveland Clinic and Mount Sinai, have likewise denounced the medication approval process and vowed not to administer Aducanumab to patients.
Furthermore, the CMS has launched a National Coverage Determination analysis to evaluate the drug's benefits to determine if they merit the $56,000 price tag. Additionally, the American Academy of Neurology has released guidance for neurologists urging them to disclose to patients the unknown potential benefits and known risks of the drug. Many neurologists have heeded this advice, and as of this writing only 3% have written a prescription for Aducanumab. More saliently, a full 18% have stated they will never prescribe the medication. In addition, Biogen has undertaken a massive advertising campaign, which seems to indicate that clinicians’ efforts are succeeding.
As I reflect on all that’s transpired around this issue, I think back to Mr. X and fear that Aducanumab would have given his wife false hope. And yet, the medical community's response these past months has given me real hope. Contrary to what I expected, clinicians still have a voice in modern medicine. I am confident that if we mobilize the way we’ve done with Aducanumab, we can fight back against the many issues that plague our medical landscape, from unaffordable medications to insurance coverage denials and social inequities.
When I graduate, I will enter a world of great injustice. Yet, I am certain that we clinicians have the collective power to combat all that goes against the Hippocratic tenets, just as we have done with Aducanumab.
What actions undertaken by the medical community have inspired you recently? Share your thoughts in the comments below.
All names and identifying information have been modified to protect patient privacy.
Lachlan Shiver is a current second-year medical student attending the USF Morsani College of Medicine. His interests include neurological research, medical humanities, and running.
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