New FDA guidelines for use of Aduhelm – a step in chasing the rainbow?
Today Biogen announced the changes highlighted in yellow below in the prescribing information for Aduhelm, recently approved for treatment of Alzheimer’s disease. There were several problems with the FDA’s initial brand label authorizing use in any patient with Alzheimer’s disease. The drug has only been studied in those with mild cognitive impairment due to Alzheimer’s and those with early-stage Alzheimer’s dementia. There have been no trials of the drug in patients with advanced Alzheimer’s disease. There are reasons to think that it will not be effective in the late stages of the disease and also that side effects may be more severe in the late stages. I strongly feel that Aduhelm should not be used in moderate and severe Alzheimer’s outside of a clinical trial until safety and efficacy have been studied in these groups.
The changes in the prescribing information to limit the use of Aduhelm to those with MCI or mild dementia due to Alzheimer’s disease are welcome and very important. This should limit inappropriate use in more advanced disease for which it is unlikely to be beneficial and may be more dangerous. Interestingly, the stock market today seemed to agree that this was a good move by Biogen. The company’s stock traded almost 4% higher on a generally down day for the market.
However, the new guidelines still do not address another shortcoming: the lack of a requirement to use Aduhelm only in those with biomarker-evidence of Alzheimer’s pathology, eg. a positive amyloid PET scan or CSF amyloid levels consistent with Alzheimer’s. Within a few years, blood tests for beta-amyloid are almost certain to be available that will easily and relatively inexpensively identify Alzheimer’s pathology. Without requiring evidence of Alzheimer’s pathology, the drug will almost certainly be used in many people with non-Alzheimer’s dementia for which it will not be beneficial. This is not a trivial objection. A drug that works by removing amyloid from the brain cannot be expected to provide any benefit for those with dementias not associated with amyloid deposition in the brain. It is not possible to reliably determine if a given case of dementia is due to Alzheimer’s disease by neurologic exam and cognitive testing alone. There must also be biomarker evidence of amyloid in the brain to confirm the diagnosis.
Biogen and the FDA have made a good start at tightening up the eligibility criteria for Aduhelm, but in my opinion, more prescribing guidance is needed.
I was shocked when the FDA approved ADUHELM after their scientific advisory committee recommended against approval because of a lack of evidence of patient benefit. That decision was based on the review of two clinical trials. One trial did not demonstrate any benefit and the other trial demonstrated a 22% decrease in cognitive decline in the treatment arm. The tightening of patient indications for ADUHELM seems to me like closing the barn door after the horse has escaped.
Implementing Dan’s recommendations would be a significant improvement in prescribing guidance for ADUHELM. We American physicians have be admonished for decades to practice “Evidence-Based Medicine.” The FDA should be held to the same standard.
The FDA scientific advisory committee structure was developed to shield FDA drug decisions from bribes, corruption and political pressure. We may never know how this decision was justified. The FDA has a public confidence problem.