Food and Drug Administration on Friday New Alzheimer’s drug approved It may modestly slow the pace of cognitive decline early in the disease, but also carries the risk of swelling and bleeding in the brain.

The approval of lecanumab, a drug marketed as Lekambi, is expected to generate considerable interest from patients and physicians. Studies of the drug – an intravenous infusion given every two weeks – suggest it is more promising than a number of other treatments available. Still, many Alzheimer’s experts said it was unexplained by medical evidence Whether Lecanbi can slow cognitive decline is something worth noting for patients.

Even a recent report of the findings of a large 18-month clinical trial, published The study, published in the New England Journal of Medicine and co-authored by scientists from the drug’s major maker, concluded that “longer trials are needed to determine the efficacy and safety of lecanumab in early-onset Alzheimer’s disease.”

The Japanese pharmaceutical company Eisai led the development and testing of the drug. It is partnering with US company Biogen, maker of the controversial Alzheimer’s drug Adhelmin, for its commercialization and marketing and the companies will split the profits equally.

Eisai said it planned to release information about the price of Leqembi (pronounced Le-KEM-bee) a few hours after the approval was announced. a preliminary report by Institute for Clinical and Economic ReviewAn independent nonprofit organization that assesses the cost of drugs said the price should be set between $8,500 and $20,600 a year to be cost-effective for patients.

In its decision, it appears that the FDA acknowledged the criticism it has received over approving Aduhelm in 2021 after both a committee of independent advisers and an FDA council of senior officials said there was not enough evidence that it Works.

Last week, an 18-month investigation by two congressional committees found that the approval process for EduHelm was “riddled with irregularities” and included an unusually close collaboration with Biogen. In response, the FDA stated “the agency has already begun implementing changes consistent with the committees’ recommendations.”

With Leqembi, the FDA initially included narrower and more cautionary language on the drug label than with Aduhelm. (It switched to the Adhelm label a month after its approval, following protests from physicians and others.)

The Lekambi label states that the drug should only be used for patients in the early and mild stages of Alzheimer’s disease, matching the condition of the patients in clinical trials of the drug. It instructs doctors not to treat patients without testing to confirm that they have one of the hallmarks of Alzheimer’s: a buildup of the protein amyloid, which Lekambi (like EduHelm) attacks.

“We’ve worked very hard with the FDA to limit the population to a very specific test, similar to clinical trials,” Evan Cheung, president and CEO of Eisai’s United States operations, said in an interview.

Of the six million people with Alzheimer’s in the United States, about 1.5 million are estimated to be in the early stages of the disease, diagnosed with either mild cognitive impairment or early-stage Alzheimer’s. How many people will be treated with Lekambi will largely depend on whether Medicare covers the drug.

Last year, the federal Centers for Medicare and Medicaid Services sharply limited Medicare coverage for Adhelmin, citing the treatment’s unclear benefits and safety risks, and allowed payment only for participants in clinical trials. This meant that very few patients could afford Adhelmin’s $28,800-per-year price tag, and the drug was effectively taken off the market.

If the agency determines that Lakenby has clear evidence of helping patients, Medicare could cover it for all eligible patients and impose only a requirement that patients’ experience be tracked.

Like Adhelm’s label, Lekembi includes warnings about brain swelling and brain bleeding and notes that patients with a gene mutation that increases the risk of developing Alzheimer’s have a greater risk of brain swelling with treatment. Is.

Lekembi’s label also includes cautionary language about taking blood thinners during treatment, which has been raised as a concern with anti-amyloid drugs but was not addressed on Adhelm’s label. The label states, “Additional caution should be exercised” when considering whether to give a blood thinner to a Lekembi patient.

Concerns about safety have been raised by reports of the deaths of three patients who experienced brain swelling and cerebral hemorrhage, two of whom were being treated with blood thinners. Those patients took part in a large phase 3 trial of the drug, during which they weren’t told whether they got it or a placebo. But he died after a phase of the trial in which he was being intentionally treated with lecanumab, known as an open-label extension study.

a matter, the subject of a Report this week in the New England Journal of Medicine, involving a 65-year-old woman who had had a stroke and, after receiving a standard treatment for stroke-related blood clots, known as t-PA, experienced severe brain bleeding and some He died days later. In an earlier article about the case journal scienceA neuropathologist who performed an autopsy said he believed Lekembi had weakened her blood vessels and made them vulnerable to rupture when she received blood clot treatment.

one in published paper Responding to the New England Journal of Medicine report, two researchers involved in Christian’s Lekemby trial claimed that “t-PA appears to be the proximate cause of death,” not Lekemby, and noted that the woman had two variants of the gene mutation. There were copies that increase the risk of inflammation in the brain with anti-amyloid treatment. But, they added, “we agree that this case raises important management issues for patients with Alzheimer’s disease.”

Leqembi – the brand name, Mr Cheung said, is based on “qembi” in Japanese, which roughly translates to “beautiful, healthy, elegant” – was flagged on Friday under the designation “accelerated approval”. The FDA can give accelerated approval to drugs of uncertain benefit if they are for serious diseases with few treatments and attack the biological element of the disease – in this case, the amyloid protein.

The quick approval for EduHelm was controversial because the data it included was contradictory—one clinical trial had failed and another nearly identical trial showed only modest benefit—and because many Alzheimer’s experts said years of data had not shown it. It was found that reducing amyloid slowed cognitive decline.

Along with Lakenby, many experts do not agree that attacking amyloid can provide substantial benefits to Alzheimer’s patients. But they say the data are clearer and more consistent than for EduHelm and may be related to the fact that Lekembi targets a different form of amyloid.

Lakenby’s quick approval was based on Phase 2 trial data, but data from a larger Phase 3 trial in recent months has supported earlier results and provided more information. The main positive result of that trial was that patients receiving Lecanbi declined more slowly over 18 months — by less than half, 0.45, on an 18-point cognitive scale that assesses functions such as memory and problem-solving. Compared to patients receiving a placebo. (Lekembi patients declined by 1.21 points, while placebo patients declined by 1.66 points.) This equates to a 27 percent slower decline.

Lekembi patients also declined more slowly on three secondary measures of cognition and daily functioning, and the data on biological markers were generally stronger for Lekembi than for a placebo.

“From a scientist’s perspective, it is exciting that an experimental treatment targeting brain amyloid in Alzheimer’s disease appears to slow cognitive decline,” said Dr. Madhav Thambisetty, a neurologist and a senior investigator at the National Institute on Aging. Said about 3 test results.

But Dr Thambisetty, who was not speaking on behalf of the federal agency on aging, said: “From the perspective of a physician caring for Alzheimer’s patients, the difference between lecanumab and placebo is not a clinically meaningful treatment effect.” Far below.”

In the Phase III trial, about 13 percent of patients receiving Lekenbi experienced brain swelling, which was mild or moderate in most cases, compared to less than 2 percent of patients receiving a placebo. . Most brain swelling causes no symptoms and usually resolves within a few months. About 17 percent of patients taking Lekembi experienced brain bleeding, compared to 9 percent of patients who received placebo. The study noted that the most common symptom of a brain bleed was dizziness.

The authors reported that “serious adverse events” occurred in 14 percent of Lekambi patients and 11 percent of those who received a placebo. About 7 percent of Lekembi patients dropped out of the trial because of negative side effects, more than twice the percentage of placebo recipients who dropped out.

Overall, the results suggest that patients in Adhelm’s trials had a significantly lower risk of brain bleeding and swelling than those in the placebo group.

Accelerated approval requires companies to conduct one more clinical trial of the drug before full approval can be considered. Mr. Cheung said that, using the results of the Phase 3 trial, Christian intends to quickly apply for full approval.

It’s unclear whether Medicare will cover Lakenby even though it has accelerated approval. The decision to limit Aduhelm’s coverage technically applies to Leqembi and other drugs in the same class of drugs — monoclonal antibodies that attack amyloid — but the Medicare agency also said it would be “aggressive” and that each Will evaluate new drug.

Health economists say full approval of Lakenby would make Medicare coverage possible.

In the interview, citing Medicare uncertainty, Mr. Cheung sought to temper expectations about how many patients might be prescribed Lekembi and how soon they could start using it. He added that, even if Medicare ends up covering the drug, in three years “we estimate that the number of individuals potentially on Lekembi is about 100,000 people.”

There are still many unanswered questions about medicine. For example, Dr. Thambisetty said, some data about the drug suggests that it can accelerate brain shrinkage, which should be investigated as it may be a sign that the pathology of the disease is worsening. Another question is whether patients with a condition are called cerebral amyloid angiopathyor CAA, caution should be exercised regarding the use of Leqembi.

Eisai’s senior vice president of clinical research, Dr. Michael Irizarry, said that, “since CAA is ubiquitous” in Alzheimer’s, it makes sense to allow patients to use Leqembi with proper monitoring because it is the least effective. With anti-amyloid monoclonal antibody was far the rate of brain swelling and bleeding.

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