Results from an 18-month study showed that a new Alzheimer’s drug can delay disease progression by up to 35.1 percent. This means that some patients had a slow decline in decline from 4.4 to 7.5 months during the study.
The drug, called donanemab, is expected to be approved by the US Food and Drug Administration (FDA) soon. This will make it the third drug available to treat the debilitating condition in the United States. However, the study also demonstrated possible serious side effects associated with the treatment, and the results make it clear that the drug is especially effective for those in the early stages of the disease. More than 6% of the 860 patients who received donanemab infusions experienced symptoms associated with brain bleeding and swelling, such as confusion, headaches and seizures. There were also 3 deaths thought to be related to the treatment. However, having a third potential treatment for this devastating disease after decades of little clinical progress is an exciting step forward. This “may prove to be just the opening chapter of a new era of molecular therapies for [la malattia di Alzheimer] and related neurodegenerative disorderswrite Dr. Gil Rabinovici and neuroscientist Renaud La Joie, both of the University of California at San Francisco. Neither investigator was involved in the study, but commented on the findings in an accompanying editorial in the Journal of the American Medical Association (JAMA). Donanemab is an anti-amyloid monoclonal antibody created by Eli Lilly and Company. It works by attacking amyloid-beta proteins in the brain and is the same type of drug as the other two approved treatments for Alzheimer’s: aducanumab, which was approved in 2021, and lecanemab, which was approved in January of this year. . The accumulation of beta-amyloid is closely linked to the progression of Alzheimer’s disease. Though debated, the hypothesis suggests that clearing amyloid plaques will help treat the condition. To test whether this was the case, the Phase 3 study of donanemab took 1,736 patients and randomly placed them into two groups who received an intravenous infusion, consisting of donanemab or placebo, every 4 weeks for 72 weeks. Patients were tested at baseline and at the end of the trial and rated on both the Integrated Alzheimer’s Disease Rating Scale (iADRS) and the Clinical Dementia Rating Scale (CDR-SB). They were also scanned during the experiment to identify levels of beta-amyloid plaques and abnormal tau proteins in their brains. This study is unique in that it divided the study groups into those with low/medium or high tau pathology – high pathology is generally thought to be associated with more advanced Alzheimer’s . The analysis revealed that disease progression slowed by more than 20% among those who received doses of donanemab compared with those who received a placebo. When the analysis was restricted to individuals with low/medium tau pathology, progress was stalled by 35.1%, based on iADRS.
Surprisingly, 47% of the low/medium group who received donanemab had no change in their CDR-SB score after one year, compared with only 29% of those who received the placebo. During the study, if a patient had a high enough clearance of beta-amyloid plaques, he was unknowingly switched from the drug to the placebo, a move intended to save money and unnecessary treatment. This occurred in 52% of patients with low/medium tau in the test treatment group. What is interesting is that such a significant removal of beta-amyloid plaques could be associated with relatively little clinical impact, again highlighting how much we still have to learn. “These findings serve to highlight the complexity of Alzheimer’s disease itself. The exceptional ability of drugs such as donanemab and lecanemab to remove amyloid, coupled with their rather subtle effect on the rate of decline of cognitive and functional measures, suggests that amyloid is probably not the only factor contributing to the progression of Alzheimer’s”. It’s important to note that there are some major limitations to the study: Almost all of the participants were white, and the ages of the participants ranged from 60 to 85 years old. The trial also ended after 18 months, though the researchers say an extension is now in the works. More data is needed before we can find out exactly who donanemab will benefit and whether the potential side effects will be worth it.