Alzheimer’s Drug Approval Brings Controversy
Our primary care doctors in Delray Beach have been receiving questions from some of our patients about the new drug the U.S. Food and Drug Administration (FDA) approved earlier this month.
The new drug, aducanumab, is the first new drug since 2003 approved by the FDA to treat Alzheimer’s disease. Marketed under the trade name Aduhelm, it is manufactured by Biogen. Biogen says it expects to charge $56,000 a year for a patient of average weight with mild cognitive impairment.
How it works
There are many forms of dementia. Alzheimer’s disease is one of them. Experts believe that between 60-80 percent of those with dementia have Alzheimer’s disease. Alzheimer’s disease is characterized by memory loss, trouble planning and performing familiar tasks.
Researchers have attributed one cause to a build-up of a type of plaque in the brain called beta amyloids. They believe this sticky compound damages communication between the cells that affect memory and eventually kill them.
Unlike other drugs on the market that are used to manage symptoms such as anxiety and insomnia, the purpose of aducanumab is to treat the cause. The cause of Alzheimer’s is the build-up of beta amyloids in the brain. It is not intended for use in those who are in the latter stages of the disease.
Biogen does not claim it stops or reverses the disease, only that it can slow its progression.
Aducanumab is administered every four weeks intravenously in a doctor’s office. Because some instances of brain swelling and bleeding resulted from the treatment, all patients will need an MRI and blood drawn at regular intervals during treatment. Some insurers may also require a PET scan or lumbar puncture (“spinal tap”) before approving the treatment.
Other common side effects noted in the trials include falls, diarrhea, headache, confusion, delirium, or disorientation.
The Alzheimer’s drug approval process
Aducanumab gained approval through the FDA’s “accelerated approval pathway.”
This means the FDA conditionally approves drugs for serious or life-threatening illnesses. In other words, if a disease is serious enough and early clinical trials appear to show that it can work, the FDA will grant an emergency authorization.
The agency hedged its authorization, however, ordering Biogen to conduct another post-approval study to prove the drug can slow the progression of Alzheimer’s disease.
The drug failed its Phase 3 clinical trials in 2019. After reanalyzing the study results, Biogen showed positive results in two trials last year.
Alzheimer’s affects some six million Americans, ruining not only their lives but impacting those of their loved ones. This has people clamoring for a cure.
The Alzheimer’s Association released a statement that read in part: “This is the first drug that slows Alzheimer’s disease.”
Critics, however, have disputed that assertion, because they say that statement is not supported by evidence. They claim the FDA submitted to pressure from Biogen and its Japanese partner, Eisai. They also claim there was pressure from desperate patients and their families.
In fact, three members of the FDA advisory panel that had been reviewing the drug took the unprecedented step of resigning in protest after the drug’s approval.
One of them, David S. Knopman, a neurologist at the Mayo Clinic, called the approval process a “sham.” In his resignation, he wrote: “Biomarker justification for approval in the absence of consistent clinical benefit after 18 months of treatment is indefensible.”
That means that there is little evidence that reducing beta amyloids (also known as a “biomarker”) slows mental decline.
Coincidentally, an unrelated CBS “60 Minutes” piece last month featured a study of those ages 90 and above. Lead investigator and neurologist Claudia Kawas told correspondent Lesley Stahl about a subject who had donated his brain for tests after he died.
The participant had years of memory problems, most likely from Alzheimer’s disease. Yet, a post-mortem examination showed zero beta amyloids present in his brain tissue.
Which was Knopman’s point. Others agree, saying the drug should have shown some cognitive improvement in actual patients, not just a reduction of beta amyloids in brain scans.
The arguments against the Alzheimer’s drug
But, you may ask if it might work, what’s wrong with approving it?
For one thing, it will now be nearly impossible to recruit volunteers who may be experiencing memory issues to volunteer for other studies. Why risk receiving a placebo in a study when you can receive this drug? This could also impact the follow-up study on aducanumab ordered by the FDA.
A second reason is stress on patients. According to Biogen, only those with mild to moderate cognitive impairment should be prescribed the drug. However, the FDA approval includes anyone at any stage of the disease. Some worry those with more advanced cases may be unable to handle the stress associated with the required tests.
The price tag is another cautionary flag. The $56,000 annual price tag doesn’t include the cost of associated tests. The tests could bring the total to over $100,000 a year for a drug that may not work. This siphons money from Medicare that might be better used elsewhere, such as in paying for caregivers to help patients remain at home longer.
In addition, families will feel pressure to subject their loved ones to the stress and expense of the treatments in the hope it might help. While Medicare or insurers will likely cover the cost of the drug, there will be expensive out-of-pocket costs, including co-pays, for an already costly illness.
If you’re considering aducanumab for yourself or a loved one, we are happy to review all the available data to help you make the best decision possible.