New Alzheimer’s drug: why the not-yet-approved donanemab aroused excitement

Two recent drugs cannot stop or reverse Alzheimer’s disease. Their results still excite neurologists. That’s because despite years of heavy investment, trials of Alzheimer’s drugs have failed one after another.

What are the findings?

Over an 18-month period, the trial met its primary endpoint of slowing cognitive decline in patients with early-stage Alzheimer’s disease. Cognitive decline slowed by 35% in those who received the drug, and it was reported that his ability to perform daily tasks decreased by 40%.

The results are based on data from 1,182 patients with intermediate levels of tau protein associated with Alzheimer’s disease severity. Interestingly, the drug slowed significant cognitive decline even when data from 552 patients with high levels of tau (representing those in late-stage disease) were added to the results. Combining the results for both groups, cognitive decline he slowed by 22% over 18 months.

More importantly, the study found that 47% of those who received the drug had no cognitive decline compared to 29% of those who received a placebo.

Indeed, these are the findings the company released in a statement, and a detailed study has yet to be published. More data may become available as the company files for regulatory approval.

“Based on these results, Lilly plans to proceed with its global regulatory submissions as soon as possible and submit to the U.S. Food and Drug Administration (FDA) this quarter. We look forward to working with regulators to achieve the fastest path to conventional approval,” Lilly said in a statement.

How do drugs work?

Donanemab is a monoclonal antibody that targets abnormal plaques of the amyloid beta protein that are characteristic of brain imaging in patients with Alzheimer’s disease. Its mechanism of action is similar to lecanemab, which was developed by Japanese-American companies Eisai and Biogen and received accelerated approval from the FDA earlier this year.

Another drug from Eisai and Biogen called aducanumab, the first Alzheimer’s drug to be approved in 2021 in decades, has a similar mechanism of action.

All three are associated with a similar side effect of temporary swelling and small hemorrhages in the brain called amyloid-associated imaging abnormalities (ARIA). Researchers believe that this class of monoclonal antibodies weakens blood vessels as they attack amyloid plaques, resulting in side effects.

“Side effects were more common with aducanumab, with no functional benefit. Lecanemab has fewer side effects and shows improved risk-offset function. Published results for this new drug show similar safety It shows that it has a profile,” said Dr. MV Padma Srivastava, Head of the Center for Neuroscience, All India Institute of Medical Sciences (AIIMS).

Eli Lilly reported that 24% of patients had transient brain swelling and 6.1% had visible symptoms. It was also reported that 31.4% of participants developed microbleeds, compared with 13.6% in the placebo group.

How would you compare the two drugs?

Although there are no trials directly comparing the results of donanemab and its predecessor lecanemab, both use similar scales to measure the effects of the drugs.

A 35% slower cognitive decline is measured using a scale called the Integrated Alzheimer’s Disease Rating Scale (iADRS). This represents 37% of the Clinical Dementia Rating Box Total (CDR-SB) used by lecanemab. For lecanemab, a phase III trial of 1,795 participants found it slowed cognitive decline by 27%.

This scale assesses patient performance in six areas: memory, orientation, judgment and problem-solving, community affairs, home and hobbies, and personal care.

Another difference between the two drugs is dosage. Lecanemab he will be given intravenously once every two weeks. Donamab, on the other hand, is given once a month and stopped when the patient’s amyloid level reaches a certain threshold.

Why are the results important?

Alzheimer’s cases are on the rise, but Alzheimer’s disease is part of it.Scientists are not sure what causes the disease, although some estimates put the burden of dementia in India rising to 14 million by 2050. has not yet reached an agreement.

Now, the success of three treatments in a row over two years in slowing cognitive decline in patients with early Alzheimer’s disease suggests that one of the main causes of the disease is abnormal clusters of amyloid-beta protein around brain cells. The theory that the

However, some believe that Alzheimer’s disease may be an autoimmune disease in which the body’s immune system cannot distinguish between brain cells and the fat that makes up the bacterial envelope.

Additionally, some believe that Alzheimer’s disease is caused by excessive deposition of iron in the brain and depletion of an antioxidant called glutathione that maintains iron levels.

“A lot of research has been done and is still ongoing,” Dr. Padma said.

But she remained cautious, saying the drug was only given to patients for a brief period of 18 months. “We don’t yet know how the disease will progress over time,” she said.

He said India should still focus on preventing Alzheimer’s disease as much as possible, as the high cost of treatment remains a major barrier to treatment.

How can Alzheimer’s disease be prevented?

Lifestyle modifications known to reduce the risk of other non-communicable diseases such as diabetes and hypertension are also associated with a reduced risk of Alzheimer’s disease. Doctors prescribe a healthy diet, regular exercise, sleep well, and reduce the risk of diabetes and heart disease. It also recommends quitting smoking and drinking less.

Beyond that, doctors suggest people, especially older people and those with a family history, need to keep their brains active. Solving puzzles, learning new languages ​​and new skills, going out and making friends all help.