The Food and Drug Administration on Friday approved a brand new Alzheimer's medication which could slow the rate of cognitive decline in the early stages of the course of the disease, but has the potential for bleeding and swelling in the brain.

The decision to allow lecanemab, the medication lecanemab which will be advertised as Leqembi will likely to draw a lot of attention from both doctors and patients. The studies of the drugan intravenous infusion that is given every two weeksindicate that it is more effective than the limited quantity of other therapies that are available. However, a number of Alzheimer's experts claimed it was difficult to determine by the evidence from medical studies whether Leqembi would slow cognitive decline to the point that it would be noticed by patients.

In a report released recently of the findings of a massive 18-month clinical study, published in the New England Journal of Medicine and co-written by scientists of the leading company responsible for the drug found the following "longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer's disease."

Eisai is a Japanese drug company was the one to lead its development, testing and production of the medication. It has partnered in collaboration with American company Biogen which is the maker Aduhelm, a notorious Alzheimer's drug Aduhelm for commercialization and marketing. The companies will share profits equally.

Eisai stated that the cost for the Leqembi (pronounced le-KEM-bee) will be $26,500 annually. It is a little less than that of Aduhelm, however, it is higher than the price suggested by some analysts.

"Based on our draft results, that price would not meet typical cost-effectiveness thresholds," the Dr. David Rind, the chief medical officer of the Institute for Clinical and Economic Review which is an independent non-profit group that studies the value of drugs. In its preliminary report in the last month, this institute stated that for a cost-effective approach to patients the cost should be placed between $8,500 to $20,600 per year.

"Given the large number of patients with Alzheimer's disease, it is particularly important that new therapies be priced in line with their value to patients," Dr. Rind said Friday.

In making its decision the F.D.A. seemed to acknowledge the outrage that ensued when it endorsed Aduhelm in 2021, after an independent advisory committee as well as an F.D.A. Council of top officials claimed there was no evidence to show that it had worked.

The week before an investigation lasting 18 months by two congressional committees revealed that the process for approving Aduhelm had been "rife with irregularities" and included an unusually close relationship with Biogen. In response to the findings, Biogen's F.D.A. stated that "the agency has already started implementing changes consistent with the committees' recommendations."

With Leqembi, the F.D.A. provided more slender and cautionary words on the label of the drug than it did initially with Aduhelm. (After protests from doctors and others, the company modified the Aduhelm label after a month following the approval.)

The Controversy Surrounding the Aduhelm Alzheimer's Drug

Card 1 of 5

An unproven drug. Aduhelm is not a drug that has been proven to work. F.D.A.'s Independent advisory panel as well as the council of agency officials of the highest rank voted unanimously that the data did not definitively prove that Aduhelm slows cognitive decline. The agency nevertheless approved the drug. It demanded Biogen the manufacturer of the drug to conduct a new trial in clinical trials, but it gave Biogen an additional eight years in order to finish the trial, while also allowing users to take the drug until evidence from the trial is available.

Concerns are increasing. Concerns about the approval process and the possibility that the F.D.A. was too close to Biogen led to investigation by congressional committees and the department's Health and Human Services inspector general. Major health institutions, like Cleveland Clinic, Cleveland Clinic and the Department of Veterans Affairs refused to accept Aduhelm.

The Leqembi label states that the drug should be prescribed only by patients who are in the moderate and early stage of the disease. similar to the those who are participating in clinical trials for the drug. It advises doctors to not treat patients without conducting tests to determine if they are suffering from one of the most common signs of Alzheimer's disease: a build-up of the protein amyloid that the drug (like Aduhelm) fights.

"We have been very diligent together with the F.D.A. to reduce the number of people to a specific group similar to the clinical studies," Ivan Cheung, the chief executive and chairman for Eisai's United States operations, said in an interview.

Around 1.5 million people out of 6 million Alzheimer's patients within the United States are estimated to be in the initial stages of the disease. They have diagnoses of moderate cognitive impairment, or Alzheimer's disease in the early stages. The number of people who will be treated by Leqembi will depend on the extent to which Medicare will cover the medication.

The Federal Centers for Medicare and Medicaid Services drastically reduced Medicare coverage for Aduhelm due to its unclear benefits and risks to safety, and permitting reimbursement only to those who participate who are in trials. This meant that a small percentage of patients could afford Aduhelm's $28,800 per year amount as well as the medication has been removed from the market.

If the agency decides that Leqembi's evidence is stronger of improving the lives of people, Medicare could cover it for all patients who are eligible and only require that the patient's experience be recorded.

Similar to Aduhelm's and Leqembi's, the label contains warnings about bleeding and swelling in the brain and mentions that those with genetic mutations that increase the chance of developing Alzheimer's have a higher chance of developing brain swelling as a result of the treatment.

The label of Leqembi also contains the word "warning" about taking blood thinners when on the medication. This has been cited as a problem with anti-amyloid drugs , but wasn't addressed in Aduhelm's label. "Additional caution should be exercised" when deciding whether to administer blood thinners to Leqembi patients The label states.

Safety concerns have been fuelled by news reports about death of 3 patients suffering from bleeding from the brain and swelling of the brain Two of them were treated with blood thinners. These patients took part in the large Phase 3 trial of the drug, in which they weren't told if they had received the drug or the placebo. However, their deaths took place following the conclusion of that trial, after they knew that they were being treated with lecanemab during what's known as an open-label expansion study.

One instance, which was that was the topic of an article article published this week by the New England Journal of Medicine was a 65-year-old woman who suffered an accident and, following receiving the standard treatment for blood clots that result from strokes called t-PA, suffered grave brain bleeding and passed away within a couple of days. In a previous article on this case, published that appeared in the journal Science, neuropathologists who performed an autopsy claimed that Leqembi damaged her blood vessels, making them susceptible to rupture after she received bleeding treatment.

In an released letter in response to the New England Journal of Medicine report, two scientists involved with Eisai's Leqembi trial claimed the fact that "t-PA appears to be the proximate cause of death," not Leqembi and pointed out that the woman was carrying two variants of a genetic mutation which increases the risk of brain swelling in patients receiving anti-amyloid treatment. However, they added "we agree that this case raises important management issues for patients with Alzheimer's disease."

Leqembi - the brand's name, Mr. Cheung said, is an adaptation of "qembi" in Japanese, which "roughly translates into beautiful, healthy, elegant" -it was approved on Friday, under a classification known as "accelerated approval." The F.D.A. may grant accelerated approval to medicines with no effectiveness if they're for grave diseases that require a lot of treatment and are aimed at a biological aspect of the illness -- in this instance amyloid protein.

The approval process was controversial for Aduhelm due to the fact that the evidence included were inconsistent the clinical trial failed, while another, nearly identical study showed little benefit and also because several Alzheimer's experts claimed that years of research had not proved that the reduction of amyloid slows the decline in cognitive capacity.

With Leqembi, a lot of experts aren't convinced that targeting amyloid could provide significant benefit to patients with Alzheimer's. They say that the evidence is more clear and consistent as with Aduhelm. It could be due by the fact Leqembi is a different type of amyloid.

Leqembi's rapid approval was dependent on phase 2 trial results, however in the last few months, evidence from a huge Phase 3 trial has supported the earlier findings and offered additional information. The most significant positive result of this study was that the patients who received Leqembi slowed down more over the course of 18 months -- less than half a percentage point, 0.45, on an 18-point cognitive scale , which measures the ability to think and solve problems -- than those receiving placebo. (Patients using Leqembi decreased in the range of 1.21 points, whereas patients who were given placebo lost 1.66 percent.) This amounts to an increase of 27 percent.

Leqembi Leqembi patients also showed declines slower on three other assessments of cognition as well as daily functioning, and data on biological markers was generally more favorable in Leqembi than for the placebo.

"From the perspective of a scientist, it is exciting that an experimental treatment targeting brain amyloid in Alzheimer's disease appears to slow cognitive decline," Dr. Madhav Thambisetty who is neurologist and senior researcher of the National Institute on Aging, expressed his excitement over the Phase 3 trial's results.

However, the doctor. Thambisetty, who was not speaking on behalf of the federal agency for aging and added: "From the perspective of a physician caring for Alzheimer's patients, the difference between lecanemab and placebo is well below what is considered to be a clinically meaningful treatment effect."

Within the Phase 3 study, more than 13 percent of the patients taking Leqembi suffered from brain swelling, that was moderate or mild generally, whereas just a tiny fraction who were given placebos experienced this swelling. The majority of the brain swelling did not result in any discomfort and usually disappeared within a few months. Around 17 percent of Leqembi patients suffered from bleeding in their brains as opposed to 9 percent of those who received the placebo. The most frequent symptom of bleeding in the brain was dizziness the study found.

The authors noted the fact that "serious adverse events" occurred in 14 percent of patients in the Leqembi trial as well as 11 percent patients who were given placebo. About 7 percentage of Leqembi patients were unable to participate in the trial due to negative side effects. This is more than double that of placebo participants who quit.

Overall, the results suggest that the risk of bleeding from the brain and swelling was much lower than that of patients who participated in clinical trials of Aduhelm.

Accelerated approval requires that companies run another clinical trial for the product before it is approved in full is considered. He said. Cheung said that, with the Phase 3 trial's results, Eisai intends to quickly seek approval for the full amount.

It's not clear if Medicare will be able to cover Leqembi as it is undergoing been approved in a speedy manner. The agency's decision to restrict coverage of Aduhelm technically is applicable to Leqembi as well as other drugs belonging to the same class of monoclonal antibodies that target amyloid however, the Medicare agency also claimed it will remain "nimble" and evaluate each new drug.

A full Leqembi approval would ensure Medicare coverage more likely health economists suggest.

The interviewer cited Medicare uncertainness in the interview, Cheung referred to the uncertainty surrounding Medicare. Cheung sought to lower expectations about the number of patients that may be given Leqembi and the speed at which they could begin using it. He stated that, even in the event that Medicare is able to cover the drug, within the next three months "we estimate the number of individuals potentially on Leqembi is probably about 100,000 people."

There are many unanswered concerns about the medication. For instance, it is said that Dr. Thambisetty noted, some studies on the drug suggest that it may cause brain shrinkage to increase that is something that should be studied because it could indicate that the pathology is deteriorating. Another issue is whether those suffering from a condition known as cerebral amyloid angiopathy also known as C.A.A., should exercise caution when using Leqembi.

Doctor. Michael Irizarry, senior vice-president of clinical research at Eisai He said that "since C.A.A. is widespread" in Alzheimer's it was logical to let patients use Leqembi in conjunction with proper monitoring since it was the monoclonal anti-amyloid antibody with the lowest risk of bleeding and swelling in the brain to date.
http://www.dream11today.com/fda-approves-leqembi-new-treatment-for-early-alzheimers/