We have been aware of Alzheimer’s disease for well over a century while still having limited treatment options. Therefore, this new drug may have been seen as a breakthrough for the company behind aducanumab, Biogen, as well as patients with Alzheimer’s disease. However, there are many concerns about the efficacy and safety of aducanumab.
Many criticisms have been made about the outcomes of the clinical trials, which were terminated early. There was a significant reduction in the amount of plaques in the brain. However, there were no significant findings in one of the clinical trials, but one trial, called Study 203, demonstrated a 22% point reduction in a dementia clinician rating scale when participants were given a high dose of aducanumab. However, that high dose also increased the rate of brain imaging abnormalities including brain swelling, fluid buildup, or microbleeds in the brain (Alexander et al., 2021). Additionally, some researchers also argued that although that these results may not necessarily translate to actual clinical benefits, such as improved memory or significant slowing of the progression of Alzheimer’s disease (Liu et al., 2021). Lastly, the cost of the drug is exceptionally high at $56,000. There would also be additional costs as imaging would be needed with administration of the drug to monitor for any brain swelling, fluid buildup, or microbleeds. Although it has been given FDA approval, the Centers for Medicare and Medicaid Services have only approved aducanumab coverage to clinical trials based on these criticisms.
Lecanemab (Lequembi) is another drug that was developed to target amyloid plaques. Similar to aducanumab, there was substantial reduction in the plaques when participants were assessed after 18 months. One study (van Dyck et al., 2023) has demonstrated moderately favorable results indicating better scores on cognitive and functional measures. Additionally, although there were some adverse outcomes, there were less demonstrable adverse effects such as microbleeds in the brain in comparison to aducanumab. It is also set at a more reasonable price point at 26,500 dollars per year, and it is covered by CMS in “appropriate settings.” Some criticism is that initial studies show that it only slows cognitive decline by about six months. Additionally, it is yet to be seen if the drug leads to real world benefit or increased functionality and decreased memory loss. It is also suspected that patients will need to undergo imaging and genetic testing to determine eligibility and having ongoing imaging studies. More studies are needed before solid conclusions about the drugs safety and efficacy can be confirmed.
The lack of substantial evidence from research has also put into question the driving hypothesis that led to the creation of medications that target plagues. The amyloid hypothesis proposes that one of the primary reasons people experience cognitive decline from Alzheimer’s disease is from accumulation of these plaques as well as other cascading effects (Jack et al., 2019). The idea is that if we stop the buildup of plaques early on into the disease, we can prevent further consequences from it. However, the research has not been consistent in supporting this hypothesis. Others have proposed a more multifactorial approach to the cause of Alzheimer’s disease, including blood vessel diseases and inflammation.
In a nutshell, aducanumab has not demonstrated significant benefit for clinical use. There is some initial evidence that lecanemab may be helpful, but the jury is still out. These drugs continue to be expensive and require significant medical tests before approval as well as during follow up visits. They are also appropriate for those diagnoses with mild cognitive impairment or the earliest stages of dementia. This drug would also not be safe for those who have had any brain bleeds, strokes, or major cardiovascular conditions. As always, it is best that you discuss these options with your doctors before pursuing a new line of experimental treatment.