Medical Fraternity Hold Their Breath for FDA's Decision on Experimental Alzheimer’s Drug - medtigo



Medical Fraternity Hold Their Breath for FDA’s Decision on Experimental Alzheimer’s Drug

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Lecanemab is an investigational drug that has been shown in clinical trials to decrease cognitive deterioration in Alzheimer’s disease patients. As per US News, the U.S. Food and Drug Administration is also considering fast clearance, with a decision likely on January 6.  

However, the medicine has been related to two fatalities from brain hemorrhages in study participants, so safety concerns could impede approval. If authorized, the treatment, manufactured by the Japanese pharmaceutical company Eisai, will become the second prescription ever approved to halt Alzheimer’s disease, following the controversial drug Aduhelm.  

Dr. Babak Tousi from the Cleveland Clinic emphasized that not every patient would benefit from lecanemab. He directed the component of the clinical trial done in Ohio at the Cleveland Clinic.  

Tousi stated that the trial was designed for patients in the early stages of Alzheimer’s disease, mild cognitive impairment, and dementia. If this treatment is approved, it will likely be prescribed to patients in the early stages of a disease who require limited assistance with everyday activities.  

Tousi remarked that the results of the 18-month research involving around 1,800 patients attracted widespread interest when they were published in the New England Journal of Medicine on December 1.  

In the trial, patients with early-stage Alzheimer’s who received lecanemab exhibited a 27% reduction in mental decline compared to patients who received a placebo. In comparison to non-users, drug users had less evidence of amyloid protein plaques in their brains.  

The accumulation of amyloid in the brain has long been a characteristic of Alzheimer’s disease. “Lecanemab accomplished exactly what it was meant to do — it eliminated amyloid plaque,” said Tousi, director of the Clinical Trials Program at the Center for Brain Health at the Cleveland Clinic.  

“Lecanemab recognizes this amyloid and aids in its elimination,” he stated. “The results revealed all of the hoped-for downstream benefits, including a reduction in biomarkers and a slower clinical decline on multiple functional and cognitive measures. Consequently, this distinction will likely result in a longer duration of independent living for patients.”  

Nonetheless, the deaths of two trial participants threw a shadow over these encouraging findings. Both died of cerebral hemorrhages that appear to be related to the use of lecanemab. According to an article published on November 27 in Science Insider, a 65-year-old lady with early-stage Alzheimer’s died of a large brain bleed that some experts relate to lecanemab. The woman suffered a stroke as well as a form of brain swelling and hemorrhage previously associated with these antibodies, according to the paper.  

Emergency room physicians at Northwestern University Medical Center in Chicago administered tissue-plasminogen activator, a common but potent clot-busting medication, to the woman (t-PA). She instantly experienced significant bleeding throughout the outer layer of her brain.  


Her spouse told Science Insider, “As soon as they injected it into her, it seemed like her body was on fire.” “She was wailing, and it took roughly eight people to subdue her. It was dreadful.” The woman died few days later, according to the case report. 

The death follows that of an 80-year-old man who participated in the phase 3 clinical trial of lecanemab. His death was associated with a probable interaction between the experimental medicine and apixaban, a blood thinner (Eliquis). The autopsy performed by neuropathologist Rudolph Castellani of Northwestern University revealed that the woman had amyloid plaques covering many of her brain’s blood vessels.  

Castellani stated that the woman received biweekly infusions of lecanemab, which appears to have irritated and weakened her blood vessels. When these veins are exposed to the clot-busting medication, they burst, a complication that can occur in traditional stroke cases. Castellani told Science Insider, “It was a one-two blow.” “There is no doubt in my opinion that this disease and death are the result of treatment. She would be alive now if she hadn’t been administered lecanemab.”  

Eisai declined to comment on the woman’s case but issued the following statement: “All available safety evidence suggests that lecanemab therapy is not related with an increased risk of mortality from any cause.” During the 18-month trial, the woman may have received either lecanemab or a placebo, but she was given the drug in the month prior to her death. She elected to get it as part of an extension of the clinical trial with an open label. 

Both the woman and the guy had extensive cerebral amyloid angiopathy (CAA), in which amyloid deposits gradually replace the smooth muscle of blood vessel walls. According to the paper, about half of Alzheimer’s patients have CAA, and many also suffer from cardiac conditions that are often treated with blood thinners.  

In these people, removing the amyloid, which medications like lecanemab are designed to accomplish, could weaken the blood arteries and make them susceptible to bleeds if exposed to blood thinners or clot busters, according to experts.  

Additional information on the woman’s case, including autopsy data, was published in the New England Journal of Medicine on Wednesday by specialists at Northwestern Medicine in Chicago. The autopsy revealed significant brain hemorrhaging and the presence of amyloid plaques in numerous blood vessels.  

The team from Northwestern believes that exposure to t-PA caused blood vessels in the patient’s brain to burst, resulting in death. “The enormous number and variance in diameters of the cerebral hemorrhages in this patient would be unexpected as a consequence of t-PA exclusively due to cerebrovascular amyloid,” they wrote. However, past usage of lecanemab may have tilted the scales and triggered the hemorrhages.  

Drs. Marwan Sabbagh and Christopher H. van Dyck stated in a journal comment to the article that they “believe that this case poses relevant management considerations for patients with Alzheimer’s disease.”  

However, they noted that variables other than the patients’ use of lecanemab could have been at play. An extended period of extremely high blood pressure may have contributed to the woman’s condition. In the man’s instance, the atrial fibrillation medication he was taking may have contributed to the bleeding.  

Additionally, Sabbagh and van Dyck stated that amyloid deposits within blood arteries have previously been observed in individuals who died after receiving t-PA. In addition to the two fatal occurrences, the clinical research revealed that 2.8% of individuals who received the medicine experienced a symptom called ARIA-E, which involves brain swelling. ARIA-E was not observed in any of the participants who received the placebo.  

However, for the millions of Alzheimer’s patients in the United States, any effective medicine could be welcome. The expectation surrounding lecanemab is a result of the controversial June approval of a comparable Alzheimer’s medicine, Aduhelm, despite the fact that trials failed to demonstrate the treatment’s efficacy and revealed significant safety hazards.  

As a result of Medicare’s decision to limit coverage for Aduhelm, citing dangers and a lack of demonstrated value, the pricey medicine was virtually sidelined.  

As with Aduhelm, lecanemab is a monoclonal antibody that targets amyloid, a molecule that tends to aggregate in the brains of Alzheimer’s patients. It is administered intravenously every two weeks. Decades of research have yielded scant evidence that removing these plaques helps with memory and cognitive difficulties. Another anti-amyloid monoclonal antibody, gantenerumab, failed to demonstrate efficacy earlier this month.  

Tousi emphasized that lecanemab will not generate a remarkable improvement in the cognitive health of Alzheimer’s disease patients. “Taking this drug does not improve your memory,” he explained. “It is a relatively new idea for many patients. It does not alleviate the symptoms, but it slows the deterioration… It is a modest advantage, but it is still an advantage. The outcomes are encouraging in the absence of other treatments.” 

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