Donanemab | Quiet Cheers

Donanemab, a new drug prescribed to people with Alzheimer’s disease, has sparked a lot of interest in whether it could represent a “breakthrough” in treating Alzheimer’s disease, the most common form of dementia. Unfortunately, there is very little to support.

On July 17, Eli Lilly, the US manufacturer of donanemab, published the results of a 1,736-person trial in the Journal of the American Medical Association (JAMA). The drug did not promise a cure, but among people in the early stages of the disease, it significantly slowed cognitive decline in 47% of those who took the drug, as opposed to 29% of those who received a placebo. About 860 people received the drug every 4 weeks for 72 weeks, and 876 did not.

damage to brain cells

Donanemab is a monoclonal antibody. Synthesized in the lab to mimic the antibodies our immune system produces to fight antigens and harmful invaders. The philosophy underlying the use of donamab is that it can be used to neutralize the accumulation of amyloid protein, which is believed to be most associated with this disease. Elevated amyloid levels trigger another protein called tau that damages brain cells, causing the cognitive decline that is typical of the disease.

Two other drugs, aducanumab and lecanemab (also monoclonal antibodies, premised on the amyloid-tau hypothesis), have also been reported to reduce amyloid levels in recent weeks. However, analysis of the trial results showed equivocal effects in reducing cognitive decline. Two trials of aducanumab showed minimal efficacy, with follow-up after 6 months revealing a 22% slower rate of cognitive decline in patients taking aducanumab compared to placebo. His 18-month trial of lecanemab in 1,800 young-onset Alzheimer’s patients reported similar results, slowing his cognitive decline by 26%. As researchers Yen Ying Lim and Emily Rozenich from Monash University in Australia said in an article for The Conversation, this effectively means a “six-month stipend.”

With donemab, people with low or moderate tau levels experienced a 35% slower decline in tau over 76 weeks than those who took placebo. However, those with high tau levels declined at a similar rate regardless of whether they received donamab or placebo. “The drug also cleared about 90% of the total amount of amyloid from the brain. Once the people’s amyloid levels were minimal, the researchers switched them to placebo. One year after the switch, patients who took donanemab continued to decline at a slower rate than those who took the placebo to begin with,” says a report on the results of the trial published in the scientific journal Nature.

cognitive decline

Patients’ degree of cognitive decline was assessed by assessing their ability to drive, pay bills, and perform errands outside the home at various intervals up to 18 months. Ultimately, there was an overall reduction in both treatment and placebo groups. The drug was ineffective in patients with mild or worse symptoms, but like aducanumab and lecanemab, patients managed to halt cognitive decline for five to six months.

An additional set of complications related to donanemab occurred in this trial. Donanemab, like lecanemab and the related drug aducanumab, can cause amyloid-associated imaging abnormalities (ARIA), a condition that can lead to fatal cerebral hemorrhages and strokes. Nearly one-fourth of his participants in Eli Lilly’s Phase 3 trial developed ARIA, and three died from the disease. ARIA was most common among study participants carrying APOE4 genetic variants that increase the risk of developing Alzheimer’s disease, according to a Nature report.

Donanemab has already been approved by the U.S. Food and Drug Administration, but it is expected to be quite expensive at an estimated $26,500, making it out of reach for most of the affected population without substantial government subsidies. While it may be too early to hope for a cure for Alzheimer’s disease, donanemab and other drugs in its class only underscore what has been known about the disease for a quarter of a century, and early diagnosis offers the best chance of managing the disease.

According to the India Dementia Report 2020, about 7.6 million people are expected to be affected by the disease in India by 2030, the majority of whom will likely be diagnosed with Alzheimer’s disease.