What is the new drug against Alzheimer’s disease, Donanemab? Could it be a turning point?

Experts pointed to several challenges with administering the therapy in the real world. These involve getting the diagnosis of Alzheimer’s disease early on, carefully selecting patients with Alzheimer’s disease who can receive the therapy, selecting eligible patients, and following them with expensive tests. and monitor for serious adverse events that could lead to death.

With the most significant impact of donanemab seen in patients in the early stages of Alzheimer’s disease, the editorial mentioned above argues that there is a need for validated tools and expertise so that the disease can be suspected by primary care physicians and diagnosed through biomarkers in specialized dementia. clinics.

New drug for Alzheimer’s disease (designed by Abhishek Mitra)

Another editorial said a special and expensive PET scan would be needed to determine levels of protein abnormalities in the brain before and during treatment. The availability of these machines is limited in clinical settings, he said. Those screened for therapy should also get tested for the APOE4 gene, which has been linked to a higher risk of adverse events. “The costs will be substantial, not only for the drug itself, but also for the biomarker and the imaging workup,” the editorial said.

In short, most patients with Alzheimer’s disease will not benefit from therapy with strict therapy selection criteria. The likely high cost of therapy will also act as a deterrent.

So, is therapy worth it? What about side effects?

The phase III study shows that donanemab slows cognitive decline in patients with early Alzheimer’s disease by 35.1% in 76 weeks. The finding was based on a study of 1,736 patients, 860 of whom received the infusion every four weeks until the beta-amyloid plaque cleared.

“This 35% lower drop is measured by various tests that look at memory and motor skills. This translates into small daily activities like talking to another person. The therapy slows the progression of the disease, it ultimately does not treat the disease,” said Dr. Pravat Mandal, a senior researcher at the National Center for Brain Research, who is working on an alternative hypothesis about the underlying cause of the disease. Alzheimer’s disease.

Although the results cannot be directly compared with the 27% slower cognitive decline with Lecanemab – the two use different scales to measure cognitive decline – the recently published study shows that Donanemab may have slightly higher adverse effects .

Besides infusion-related reactions, the main adverse effect of drugs that remove amyloid-beta proteins is amyloid-related imaging abnormalities (ARIAs) such as swelling or bleeding in the brain, most of which are asymptomatic. The study showed that 24% of participants who received Donanemab had an ARIA involving brain swelling and 19.7% had an ARIA involving bleeding in the brain. Three treatment-related deaths were also reported in the study.

Many experts have always preferred Donanemab because the infusion must be given every four weeks instead of every two weeks with Lecanemab. Patients switched to placebo after reaching a certain level of protein clearance in the Donanemab study. “This is a welcome difference for patients and payers, limiting infusion-related burdens as well as longer-term costs,” the editorial said.

What are the doctors saying?

Dr. Mandal believes that given the enormous costs, “it is inadvisable to administer the therapy for limited benefits; unless someone has the money and really wants to go. As I said earlier, the therapy is also not a cure, which means the benefits will be for a limited time.

Dr PK Sethi, a neurologist at Sir Ganga Ram Hospital, says he will take a wait-and-see approach. “It’s a brand new drug; we do not yet know all the adverse effects that this could cause. We have to wait and see what happens when the drug is given to larger populations. This is besides the high cost of therapy. We have to do a cost-benefit analysis,” he said.

Why should we focus on other modalities?

Although the scientific community has been excited that a drug for Alzheimer’s disease has been shown to be effective and has been approved, there is an ongoing quest to find something better. “Alzheimer’s disease has multiple modalities and we would need various therapies to deal with it. Although beta-amyloid protein therapy has been at the forefront, there is also a need to investigate other targets,” Dr. Mandal said. His team is studying the impact of iron buildup and oxidative stress in the brain resulting from declining levels of an antioxidant called glutathione.

Dr. MV Padma Shrivastav from All India Institute of Medical Sciences had previously said the indian express“A lot of research has taken place and is continuing with the different mechanisms of Alzheimer’s disease in mind and so far most has not been spot on. This is one of the reasons for the craze for these drugs. But, there are more drugs in the pipeline with several different targets.

One of the editorials quoted above stated: “Ultimately, it seems likely that a combination of drugs targeting additional molecular pathways implicated in the pathophysiology of Alzheimer’s disease will be required to more profoundly affect the trajectory of disease.”