In a surprising turn of events, the US Food and Drug Administration (FDA) has postponed its decision on the approval of donanemab, a potential breakthrough drug for Alzheimer's disease. Pharmaceutical company Eli Lilly had released data from a clinical trial earlier this year, claiming that the drug could slow cognitive and functional decline in patients by 35% over 18 months.

The findings sparked optimism among experts, with some calling donanemab the "beginning of the end" for Alzheimer's disease. However, the FDA announced on March 8th that it would convene an independent panel to further scrutinize the safety and efficacy data of the drug, pushing back the decision until later in 2024.

The delay by the FDA has come as no surprise to Dr. Timothy Daly, a dementia researcher, who contends that quantifying the benefits of drugs like donanemab remains challenging compared to their potential harms. Donanemab, along with other highly anticipated drugs such as aducanumab and lecanemab, belong to a class of medications known as novel monoclonal antibodies, targeting amyloid proteins in the brain that are associated with Alzheimer's disease.

While these drugs have demonstrated the ability to reduce amyloid levels, concerns have been raised about their side effects. Approximately three out of ten patients who participated in clinical trials for lecanemab or donanemab developed amyloid-related imaging abnormalities (ARIA), which can result in brain swelling or hemorrhaging. While most cases were minor and resolved without symptoms, a small percentage experienced more severe effects, sometimes resulting in death, particularly among those taking blood-thinning medications.

Furthermore, the long-term effects of these drugs, including potential brain shrinkage, remain uncertain. Critics argue that media reports have overstated the benefits of these drugs, as efforts to translate the clinical data into meaningful terms for patients have led to speculative interpretations.

Edo Richard, a professor of neurology, acknowledges that these drugs effectively remove amyloid proteins from the brain but questions their impact on slowing cognitive decline. According to Richard, previous research has shown that amyloid proteins are present in both individuals with dementia and those without it, suggesting that their reduction does not necessarily correlate with improved cognitive function.

The controversy surrounding the approval of Alzheimer's drugs came to the forefront in 2021 when the FDA approved aducanumab despite concerns about its efficacy, leading to the resignation of three advisory committee members. Subsequently, the drug faced limited usage due to Medicare's decision not to cover it. Similar skepticism from regulators was seen in Australia, where the Therapeutic Goods Administration found no evidence of clinically meaningful efficacy for aducanumab.

Beyond the limited clinical benefits of donanemab, patients also face logistical challenges. The drug requires intravenous infusion at medical facilities every two to four weeks, along with regular testing, amounting to significant financial and emotional burdens for vulnerable individuals and their families.

The focus on drugs targeting amyloid buildup in Alzheimer's disease has drawn criticism for diverting attention from alternative hypotheses and preventive measures. Researchers have identified various modifiable risk factors associated with dementia, such as air pollution, obesity, depression, and education levels. However, experts argue that addressing these factors requires governmental intervention to create a fairer and more dementia-resilient society.

Despite the collective desperation for effective treatments for Alzheimer's disease, scientists and patients must remain objective when evaluating the evidence. The FDA's decision to seek further scrutiny of donanemab highlights the need to fully understand its efficacy and safety before widespread approval.

As the journey towards finding a cure for Alzheimer's disease continues, it is crucial to consider not only pharmaceutical interventions but also broader societal factors that contribute to dementia risk.