A newly approved Alzheimer’s drug will be available to patients in the coming days, according to its maker, the Japanese pharmaceutical company Eisai.
The drug, called Leqembi, has been shown in clinical trials to slow the progression of Alzheimer’s disease in people with mild cognitive impairment or early-stage disease. It is not a cure.
Leqembi targets a type of protein in the brain called beta-amyloid, which scientists have long thought was a major cause of the disease.
Given every two weeks as an infusion, patients will need to visit a hospital or clinic twice a month to receive the treatment. It also comes with a hefty price tag: $26,500 a year.
While Leqembi offers hope to patients and their families, experts say there are still some key unanswered questions about the drug, including about its safety and efficacy.
Here are questions that experts still have about Leqembi.
Will patients notice a difference?
Although clinical trials found that Leqembi slowed the progression of Alzheimer’s disease compared with a placebo, experts called the drug’s effect «modest» and said it’s unclear whether it will lead to noticeable changes in people’s daily lives. .
on the drug Phase 3 clinical trialthe researchers observed cognitive decline over 18 months in nearly 1,800 people given either the drug or a placebo.
Cognitive impairment was measured using a scale which focused on how well patients are doing in six areas: memory, orientation, judgment and problem solving, community issues, home and hobbies, and personal care.
For each category, patients are on a 5-point scale: 0 is normal, 0.5 is questionable dementia, and 1, 2, and 3 are mild, moderate, and severe stages of dementia, respectively.
The scoring method is «very subjective,» said Dr. Ronald Petersen, a neurologist at the Mayo Clinic in Rochester, Minn., because the scores are based on questions researchers ask patients. That said, it’s currently the best method researchers have for quantifying the severity of symptoms in patients, he said.
The researchers added up the scores and then looked at how much they changed over the course of the trial in people who got Leqembi compared to people who got a placebo.
At 18 months, patients in the Leqembi group had a mean score of 1.21 on the Clinical Dementia Scale and the placebo group had a score of 1.66, a difference of 0.45, or a rate of decline of one 27% slower.
That difference is small, said Dr. Alberto Espay, a neurologist at the University of Cincinnati School of Medicine, and below the threshold of what would be clinically significant for a patient.
It is unlikely that patients or their families «will be able to tell the difference,» he concluded.
Petersen, however, was more optimistic. «It doesn’t stop the disease, it doesn’t make it better, but it might slow down the rate of progression,» he said.
Who will benefit from Leqembi and for how long?
Leqembi is only approved for patients with mild cognitive impairment or who are in the early stages of Alzheimer’s disease.
A sub-analysis of data from Eisai’s clinical trial found that the drug seemed to work better in older people compared to younger people and in men versus women, which puzzled Dr. David Rind, a primary care physician and medical director of the Institute. of Clinical Medicine and economic review, a group that determines fair drug prices.
“It makes you wonder if lecanemab is doing something we don’t fully understand yet,” he said, using the generic name Leqembi.
Donna Wilcock, assistant dean of biomedicine at the University of Kentucky, said more research is needed.
«The short answer is: we really don’t know why this is happening right now,» he said. «We can all try to speculate on what that means,» but ultimately the findings will need to be further investigated in additional studies.
Still, the under-analysis is not a reason not to offer Leqembi to certain groups, Wilcock said. «I think there’s enough information out there that the decision should really be up to the doctor and the patient.»
In addition to questions about who will benefit the most, there are also questions about how long the drug will benefit patients.
The results from Eisai Phase 3 only looked at the effects of the drug over 18 months. It’s not clear how effective the drug will be after a longer period of time, Petersen said.
The 27% slowdown could «have an increasing impact over 24 months or 36 months or 48 months and could be more significant going forward,» he said. «I don’t think it’s accurate to portray this as a forever linear effect.»
Wilcock said that many colleagues he has spoken with are also «pretty confident» that the positive benefits of the drug will increase over time.
How safe is Leqembi?
According to the Food and Drug AdministrationLeqembi can cause cerebral hemorrhage or swelling of the brain, side effects that are of particular concern to researchers after reports of three deaths of the patients who received the drug. In response to the first two reports of deaths, Eisai has denied a link to Leqembi.
Petersen said the brain bleeding and brain inflammation are likely caused by the way the drug works: it removes amyloid from brain cells, but, in the process, it also removes amyloid from blood vessel walls, which can cause the brain to «leak.»
Side effects are also seen with another Alzheimer’s drug, Biogen’s Aduhelm, which also targets amyloid, Wilcock said.
About 12.6% of patients who received Leqembi in clinical trial developed brain swelling, compared with 1.7% of those in the placebo group. About 17% of the Leqembi group experienced brain bleeds, compared with 9% of the placebo group.
The company noted that many of the people found to have brain swelling did not have any symptoms as a result.
Because Eisai’s phase 3 trial only lasted 18 months, it’s unclear how common the condition may be, or if it becomes more common the longer a person takes the drug, Espay said.
Reports of brain hemorrhage and brain swelling «may just be the tip of the iceberg,» he said.
The condition is «potentially very serious,» Petersen said, «there’s no question about it.»
He said that people who contract Leqembi will need to be closely monitored, but added that the side effects should be manageable.