Patients and doctors await FDA decision on Alzheimer’s drug

Lecanemab: An drug that has been shown in trials to slow cognitive decline in people with Alzheimer’s disease.

It is also scheduled for expedited approval by the U.S. Food and Drug Administration, with a decision expected by January 6.

However drag It has also been associated with two deaths from cerebral hemorrhages among those who used it. trialso safety concerns may threaten approval.

If approved, the drug, made by Japanese pharmaceutical company Eisai, would be the second drug approved to slow Alzheimer’s disease, after the controversial drug Aduhelm.

Not all patients will benefit from lecanemab, stressed Cleveland Clinic physicians. Dr. Tusi RoundHe led some of the clinical trials conducted at the Cleveland Clinic in Ohio.

“This trial was designed for patients with early-stage Alzheimer’s disease, mild cognitive impairment, or early-stage dementia,” Tousi said. “If this drug is approved, it will probably be for people in the early stages of the disease who do not require minimal support for activities of daily living.”

Results from the 18-month study of approximately 1,800 patients were announced on December 1. New England Journal of Medicine, Toushi pointed out.

The trial showed that patients with early-stage Alzheimer’s disease who took lecanemab experienced a 27% reduction in mental depression compared to patients in the placebo arm of the trial. It also showed that drug users had less evidence of amyloid protein plaques in their brains compared to non-users.

Amyloid accumulation in the brain has long been a hallmark of Alzheimer’s disease.

“Lecanemab clearly served the purpose for which it was designed. amyloid plaquesaid Toshi, who heads the clinical trial program at the Cleveland Clinic Center for Brain Health.

“Lecanemab identifies this amyloid and helps the body clear it,” he explained. “The results showed all the downstream effects we were hoping for in terms of reduced biomarkers and reduced clinical decline in several functional and cognitive measures. It may lead to longer periods of independent living for patients.”

Two patient deaths raise questions

Still, the deaths of two patients enrolled in the trial overshadowed these promising findings. Both died from cerebral hemorrhages that were likely related to the use of lecanemab.

In one case, a 65-year-old woman with early Alzheimer’s disease died of a massive cerebral hemorrhage that some researchers have linked to lecanemab, according to a report published Nov. 27. science insider.

The woman had a stroke, the kind of brain swelling and bleeding previously seen with such antibodies, the report notes.

An ER doctor at Chicago’s Northwestern University Medical Center treated a woman with tissue plasminogen activator (t-PA), a common but potent clot-busting drug. She soon had a massive hemorrhage all over the outer layers of her brain.

“As soon as they put it on her, it felt like her body was on fire,” her husband said. science insider“She was screaming. It took eight people to hold her down. It was terrifying.”

According to case reports, the woman died a few days later.

This death follows that of an 80-year-old man who was participating in a Phase 3 clinical trial of lecanemab. His death was linked to a possible interaction between an drug and a blood thinner called apixaban (Eliquis).

Rudolph Castellani A Northwestern neuropathologist who performed an autopsy on the woman determined that she had amyloid deposits surrounding much of her brain. blood vessel.

Castellani said the woman was being injected with lecanemab every other week, which appeared to have inflamed and weakened her blood vessels. These blood vessels rupture when exposed to thrombus buster. This can occur even in the case of conventional stroke.

“It was a one-two punch,” Castellani said. Science Insider. “There is no doubt that this is treatment-related illness and death. Had the patient not taken lecanemab, she would be alive today.”

Eisai declined to comment on the woman’s case, but the company issued a statement. statement “All available safety information indicates that lecanemab therapy is not associated with an increased overall risk of death or an increased risk of death from any specific cause.

The woman may have received either lecanemab or placebo during the 18-month trial, but definitely received lecanemab in the month before death. She chose to receive it as part of an open-label extension of the clinical trial.

weakened blood vessel

Both women and men had extensive cerebral amyloid angiopathy (CAA), a condition in which amyloid deposits gradually replace smooth muscle in the vessel walls.

Nearly half of Alzheimer’s patients have CAA, and many also suffer from heart disease that is usually treated with blood thinners.

explained by an expert science insider In these types of patients, stripping away the amyloid, as drugs like lecanemab do, can weaken blood vessels and make them more prone to bleeding if exposed. blood thinner Or thrombus buster.

Details of the woman’s case, including autopsy results, were released Wednesday. New England Journal of Medicine by a doctor at Northwestern Medicine in Chicago. An autopsy confirmed extensive cerebral hemorrhage and amyloid deposits in many blood vessels.

The Northwestern team believes that exposure to t-PA caused blood vessels to burst throughout the patient’s brain, leading to death.

“The variability in the number and size of cerebral hemorrhages in this patient is unusual for a complication of t-PA associated solely with cerebrovascular amyloid,” they wrote, although prior use of lecanemab may have unbalanced it. , which may have caused bleeding.

and journal response To the article Dr. Marwan Sabbagh and Christopher H. van Dyck said, “We agree that this case raises important management issues for patients with Alzheimer’s disease.”

However, they noted that factors other than patient use of lecanemab may be involved. In this woman, a prolonged and very high blood pressure may have contributed. In men, drugs taken to fight atrial fibrillation may have contributed to the bleeding.

Sabbagh and van Dyck also said: amyloid deposits It has been previously seen in blood vessels in people who died after ingesting t-PA.

In addition to the two fatal cases, clinical trials also showed that 2.8% of participants who took the drug had a symptomatic side effect called ARIA-E, involving swelling of the brain. ARIA-E was not seen in participants receiving placebo.

risks and benefits

But for the millions of Americans with Alzheimer’s disease, any beneficial drug could be welcome.

Rising hopes over lecanemab continue in controversial June approval Studies of a similar Alzheimer’s drug, Aduhelm, did not prove the treatment was effective and presented serious safety risks.

Post Medicare exclusive Citing risks and unclear benefits, Aduhelm’s report essentially sidelined expensive drugs.

Like Aduhelm, lecanemab is a monoclonal antibody given by infusion every two weeks that targets amyloid, a protein that tends to aggregate in the brains of people with Alzheimer’s disease. Years of research have found little valuable evidence that removing these plaques actually helps with memory and thinking problems. Earlier this month another anti-amyloid monoclonal antibody, handsome bdid not show any benefit.

Tousi emphasized that lecanemab does not dramatically improve cognitive health in people with Alzheimer’s disease.

“This drug does not improve your memory,” he said. “This is a new concept for many patients. It doesn’t treat the symptoms, but it slows down the decline. …Small benefit, but nonetheless. In the absence of other treatments, the results are promising.” ”

Copyright © 2022 health day. all rights reserved.