With little data available, experts question the usefulness of Eisai, Biogen’s new Alzheimer’s drug

Experts are torn about the significance a closely watched experimental drug for Alzheimer’s disease could have for patients, now that its developers have released the much-anticipated results of a large clinical trial.

The trial, which recruited nearly 1,800 participants with early-onset Alzheimer’s disease, found that those taking the drug declined significantly more slowly than those given a placebo, as measured by a scoring system that rates cognition and function. Both groups declined further over the 18-month study period, but scores in the drug arm fell nearly half a point less than the placebo arm, reflecting a 27-month slower trajectory. %.

These results meant the drug, called lecanemab, met the study’s primary goal – the first clear success for a drug of its kind in a late-stage trial. Analysts expect the positive result to support Eisai, the Japanese pharmaceutical company behind lecanemab, in its efforts to bring the drug to market. Eisai is co-developing lecanemab with Biogen and earlier this year formally submitted an application for approval to the Food and Drug Administration based on data from previous studies.

“Today’s announcement gives patients and their families hope that lecanemab, if approved, has the potential to slow the progression of Alzheimer’s disease and have a clinically meaningful impact on cognition and function,” Biogen CEO Michel Vounatsos said in a statement Tuesday.

Still, with little data available, doctors and researchers aren’t sure what to make of lecanemab. Some say they worry the drug won’t work for large segments of the Alzheimer’s population, or that when it does, the overall effects will be so modest that patients don’t notice them.

“It does better than the placebo, but not much better,” said Constantine Lyketsos, director of the memory and Alzheimer’s disease treatment center at Johns Hopkins Medicine, who consulted with Eisai and other pharmaceutical companies. “I would like to see more like a two or three point difference produced by the drug [on that scale]because it really brings us closer to meaningful change.

What a significant change looks like may also depend on the course of a patient’s disease. Earlier, small changes in the 18-point symptom scale used in the trial may indicate more noticeable declines in function, such as tasks becoming harder to perform or new difficulties finding one’s way. Later, when the disease takes root more strongly, a change of half a point may have less impact.

So far, lecanemab appears to be only marginally more effective than another Alzheimer’s disease treatment already marketed by Biogen and Eisai. The use of this drug, Aduhelm, has been severely restricted, with many insurance companies balking at its price and questioning the conflicting data that supported its controversial approval in June 2021.

Still, for some experts, the results released Tuesday represent a rare victory in a field marred by setbacks.

Robert Vassar, a professor of neurology and cell and developmental biology at Northwestern University, said lecanemab “won’t be the ultimate solution, but it will be one of many tools that the doctor will use at the future for treating Alzheimer’s disease. And Thomas Wisniewski, director of the Alzheimer’s Disease Research Center at NYU Langone, argued that there are “significant differences in the quality of evidence in the history of Aduhelm” compared to lecanemab.

“It seems to be a lot cleaner,” Wisniewski said. “All the data points in a similar direction, so there are no inherent contradictions as far as we can tell.”

Like Aduhelm, lecanemab is an antibody therapy designed to break up aggregates of beta-amyloid, a protein that has been a focus of Alzheimer’s disease research for decades. Almost all amyloid-targeting drugs have failed key studies, prompting debate about whether it would be better to spend time and resources testing other hypotheses.

The positive data for lecanemab is important new evidence supporting this “amyloid hypothesis,” but the debate over the protein’s role and significance is not likely to end.

“There will probably be a maximum effect of these types of drugs on the brain,” said Eliezer Masliah, director of the division of neuroscience at the National Institute of Aging. “Trying to determine the clinical significance of this is going to be the work ahead.”

Howard Fillit, co-founder of Alzheimer’s Drug Discovery Foundation, a nonprofit research funding organization, said in a statement that while the results reported by Eisai are encouraging, he believes “anti- amyloids will at best provide additional benefit and there is still a pressing need for the next generation of drugs aimed at other targets.”

Vassar, on the other hand, said he thinks the new lecanemab data is exciting and helps confirm the amyloid hypothesis. Vassar consulted for Eisai.

Wisniewski also said he found the new results exciting, even though they “weren’t hugely clinically meaningful.”

“There seems to be a clear cognitive benefit,” he said, “and the FDA may well approve it next year.”

Eisai and Biogen are awaiting a decision from the FDA in early January on accelerated approval and plan to use Phase 3 data to seek full clearance.

Along with its effectiveness, the FDA will also assess the safety of lecanemab. In the large clinical trial, researchers found more abnormalities in brain scans of the drug arm than its placebo counterpart. Eisai reported that 12.5% ​​of lecanemab-treated patients experienced brain swelling and 17% experienced small-scale brain bleeds, although the company said only a small fraction of those cases were symptomatic.

These symptoms and their severity will be of interest as more data becomes available, according to Wisniewski. “It is clear that this antibody therapy, like others, requires very close monitoring of patients.”

For Lyketsos, a key sticking point will be the ability to apply new findings to the wider Alzheimer’s community.

Eisai made an effort to recruit a more diverse group of trial volunteers. Twenty-five percent of U.S. participants were Hispanic or African American, Eisai said, far more than was typical in previous Alzheimer’s drug studies. However, his study also recruited participants who were relatively younger and healthier than the average Alzheimer’s patient, and whose disease was at an early stage.

“A lot of these variables that are different, especially comorbidities and age, really matter for the outcome,” Lyketsos said.

“I don’t know if I can say ‘my patients should definitely take lecanemab,’ he added. “I’ll probably say, ‘We’ll give it a try, see how it goes for you. But recognize that there are a lot of unknowns, and it will be hard for you to know that you are actually benefiting from them.

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