Summary: Recent approval of the drug by the US FDA to treat Alzheimer’s has raised a lot of controversies. It appears that its approval is supported by weak data. The US FDA approved the injectable monoclonal antibody called aducanumab to treat Alzheimer’s. It targets the amyloid plaques formed in the person’s brain living with Alzheimer’s. However, targeting these amyloid plagues does not appear to prevent or manage the condition effectively. Two phase-3 clinical trials had inconclusive findings, according to experts. However, the US FDA and the drug manufacturer Biogen claim that it is effective at higher dosages.
US FDA recently approved aducanumab for Alzheimer’s treatment. However, there does not seem to be enough evidence that it works. It appears to have marginal to no benefit, and at the same time, might cause severe side effects.
Researchers have been studying Alzheimer’s for more than 100 years, yet they appear to know little about it. There is no firm understanding of its etiology and pathogenesis. It seems that the disease is heterogeneous, thus caused by a combination of factors like aging, vascular conditions, and much more1.
Familial history of Alzheimer’s has poor predictive value. The disease may affect even those with no family history of Alzheimer’s. There are no early tests that may help predict the risk of Alzheimer’s confidently.
So, why the new drug aducanumab is so controversial?
It appears that the drug is trying to manage something which has something to do with Alzheimer’s, but its role is unclear. This particular drug tries to get rid of the accumulation of amyloid plaques.
There is no doubt that amyloid plaques are present in all cases of Alzheimer’s. However, it is not clear what causes the accumulation of these plaques and the death of brain cells. In addition, it is not clear if amyloid plaques have a central role in the disease or are just one of the changes caused by poorly understood etiological factors/disease-causing factors.
Amyloid theory or hypothesis has just become too strong and central to Alzheimer’s development. It is not the first drug targeting these plaques. However, early approaches targeting these plaques have failed. But, even worse, data from clinical studies of the new drug isn’t encouraging either, despite potential insights from interventional pain management in Saint Louis.
The data of clinical trials is so discouraging that members of the advisory committee to the US FDA advised against the drug’s approval. And yet, US FDA went forward with its approval. Furthermore, its manufacturer priced the drug at 56000 USD for annual treatment, making it one of the most expensive medications in US history. The pricing also raises specific ethical concerns.
So, what the company and the US FDA is saying? The pooled data of the two phase-3 trials did not show much benefit, with one trial showing no benefit at all and the other only marginal benefit. However, the company and US FDA say that they saw that it helped better at higher dosages. It’s a statement expert are finding hard to accept.
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Thus, for example, analysis of data by neutral experts did not show any benefit from the drug. A study published in Alzheimer’s & Dementia journal concluded that two clinical trials with the drug called EMERGE and ENGAGE have failed to confirm the benefit. However, further clinical trials with higher dosage might be justified2.
Further, experts point out that Alzheimer’s seems to have achieved its peak. Thus, it appears that lifestyle modification may have greater benefit in reducing its risk than using toxic drugs to clear amyloid plaques.
Thus, a study regarding dementia prevention published in the journal The Lancet says that reducing alcohol intake, quitting smoking, preventing head injuries, reducing air pollution, improving education, reducing hypertension, managing obesity, reducing depression, increasing physical activity, preventing diabetes, and increasing social intervention may delay dementia in as many as 40% of cases3.
References
- An Y, Zhang C, Siyu H, Yao CX, Zhang L, Zhang Q. Main hypotheses, concepts and theories in the study of Alzheimer’s disease. Life Science Journal. 2008;5.
- Knopman DS, Jones DT, Greicius MD. Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019. Alzheimer’s & Dementia. 2021;17(4):696-701. doi:10.1002/alz.12213
- Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020;396(10248):413-446. doi:10.1016/S0140-6736(20)30367-6
