Over the years Alzheimer’s patients and their families have seen more than one hundred twenty drugs that were developed for the treatment of Alzheimer’s have failed. For a while, it appeared that Biogen’s aducanumab would be added to the list. However, a recent article in the Wall Street Journal announced Biogen’s unprecedented move to resurrect two failed clinical trials.
The company will seek FDA approval in early 2020. The drug had been tossed aside after disappointing results from a December 2018 clinical trial.
The FDA had granted aducanumab fast track (expedited review) designation in 2016. The drug at that time was considered to have the highest potential for success in the treatment of early-stage Alzheimer’s.
Why The Reversal?
Participants in one of the trials who had a specific genetic variant (variation in the DNA sequence) continued to receive treatment with aducanumab for a longer period and at higher doses. This was not reported in the final results. These participants exhibited a significantly slower cognitive decline.
As a result of these findings, the company will be able to submit its application for approval. From now on, it will include all trial participants in its analyses.
FDA Intervention
After reporting its mediocre trial results, Biogen met with FDA officials who recommended additional analyses. One of the officials suggested that the trials be based on initial clinical data that identified patients who may benefit most from treatments in addition to the customary randomized double-blind protocol.
As it turned out, Biogen’s trials did show how tailoring the trials can bring about positive results.
Two important factors emerged from Biogen’s updated analyses. First, it is critical to be aware of the dose of aducanumab that travels across the blood-brain barrier and second it is important to track the duration of treatment.
Prior to setting the clinical trial findings aside, it was later discovered that Biogen investigators had not included several patients who had received higher doses of the drug nor had they included patients who had taken the drug for extended periods.
About Aducanumab
The experimental drug aducanumab is an antibody that zeros in on beta-amyloid (amyloid-β) proteins. These proteins are thought by researchers to be responsible for plaque forming in the brain. The popular opinion among scientists is that plaque in the brain causes or contributes to Alzheimer’s. But so far every late-stage study targeting amyloid-β protein in the brain has failed.
When Biogen initially set its clinical trial aside, some researchers and journalists suggested halting further work connected to the amyloid hypothesis, even though a wealth of evidence had accrued supporting the theory over the past thirty-five years.
Biogen recently announced that patients who had participated in the trials may be able to participate in future trials.
About Alzheimer’s
Approximately six million Americans over the age of 65 may have Alzheimer’s.
Currently Alzheimer’s disease is irreversible. It is a progressive brain disease that destroys memory, thinking skills, and at a later stage prevents patients from being able to go about their daily lives. It is known to be a major cause of dementia among the elderly.
The first symptoms of Alzheimer’s generally begin in the patient’s mid-sixties. It is rare that someone in their thirties to mid-sixties has the disease.
The most prominent features of Alzheimer’s are tangles and plaques in the brain as well as the connections between nerve cells in the brain being interrupted.
Researchers suspect that there are also other complex changes that take place in the brain of an Alzheimer’s patient. Additional information about Alzheimer’s is available here.
Waiting for FDA Approval
A scientist commented that if the FDA does not approve the drug, there is still evidence that the anti-amyloid hypothesis has merit. One observer thinks that the drug’s modest effect may not be sufficient to qualify for coverage by insurance companies.
The controversy surrounding aducanumab will continue.
