Controversy has swirled about the approval by the USA Food and Drug Administration (FDA) of aducanumab, a new drug for Alzheimer’s disease. This drug is an antibody against a toxic protein (called the A-beta or amyloid beta protein) that builds up in the brains of people. This toxic protein build-up eventually leads to the formation of amyloid plaques which are hallmarks of the brain pathology of Alzheimer’s disease. Previous similar trials have yielded negative results.
Biogen, a drug company, conducted 2 major trials of aducanumab for people with Mild Cognitive Impairment (MCI) or early Alzheimer’s disease and evidence of amyloid plaque build-up in their brain using PET brain imaging. MCI is a pre-dementia stage defined as having subjective and objective evidence of decline in cognition, particularly memory.
In March 2019 Biogen halted their trials of aducanumab as analysis indicated that continuation was futile. Later that year, after Biogen’s re-analysis of their data, they reported that participants who were on high dose of aducanumab showed benefit in cognition in one of their two major trials as well as reduction in the amyloid plaques in their brains.
Biogen worked with the FDA and applied for approval of the drug. Despite the FDA’s own external advisory group voting almost unanimously against approval, the FDA gave it Accelerated Approval based on an intermediate outcome. That is reduction of the amyloid protein build-up/plaque in the brain (visible on specialised PET Scans) even though the FDA noted the lack of convincing evidence of cognitive benefit.
Many experts decried the decision and three members of the FDA Advisory Committee resigned. Proponents of the drug drew an analogy with the statins (such as Crestor, Lipitor) that are widely prescribed help to reduce heart attacks by lowering cholesterol. Cholesterol reduction has been associated with decreased rates of heart attack and mortality have been dropping.
What are the downsides of aducanumab?
- Expense: U.S.$56,000 yearly.
- Administration: monthly intravenous infusions.
- Duration: at least for one year, maybe longer.
- Side effects: within the first four months, about one in three people will have headaches, difficulty with vision, disorientation and confusion, swelling in the brain and micro-haemorrhages. Symptoms generally subside over time.
Where does this leave us in Australia regarding aducanumab?
Biogen would need to make an application to the Therapeutic Goods Administration [TGA] which would need to consider its efficacy and safety. If approval were given, the next stage would be for Biogen to make an application to the Pharmaceutical Benefits Scheme (PBS) for subsidisation as the cost would be beyond many people.
Even if aducanumab proves to be successful, it is only indicated for Alzheimer’s disease, which is just one type of dementia. It will not work for other types such as vascular dementia, Lewy body dementia or fronto-temporal dementia. Nor do we know if it will be of use in people with more advanced Alzheimer’s. The hope is that it may be used in people with pre-Alzheimer’s – some symptoms and brain imaging showing amyloid plaques – to stop it progressing to clinically diagnosed dementia.
The danger with many news or stories about breakthroughs and cures is that sensationalism can lead to false hopes. Opinion among experts remains divided about how useful aducanumab will be. While it does give hope, it may be prudent to wait for more evidence.