But the detailed results also concluded that the drug, lecanemab, was associated with “adverse events” and warranted more study.
Marwan Sabbagh, a neurologist at the Barrow Neurological Institute and a co-author of the study, described two patient deaths that had raised concern about the safety of the drug ahead of Tuesday’s presentation. “Causality with lecanemab is a little difficult,” he said, noting that both patients, a 65-year-old woman and an 87-year-old man, had underlying health issues. Though the rate of brain bleeding was low, he said, the risk increases with medications to prevent blood clotting.
“That might be a relative risk that needs to be managed,” he said at the Clinical Trials in Alzheimer’s Disease conference late Tuesday.
Eisai confirmed the two deaths Tuesday night and denied they were related to the drug.
The new details have been the subject of intense anticipation by doctors and Wall Street since Eisai and Biogen announced in September that lecanemab had slowed cognitive decline by 27 percent compared with a placebo.
Lecanemab has emerged as the front-runner among a class of drugs that seeks to remove clumps of a protein in the brain called amyloid beta, which researchers have long suspected plays a role in Alzheimer’s. The Food and Drug Administration is set to make a decision on accelerated approval of the drug as early as January. That could translate into a multibillion-dollar prize for treating a progressively debilitating disease that affects 6 million Americans and has few approved therapies.
“It’s the best data we’ve seen in Alzheimer’s in a pivotal trial,” Myles Minter, a biotechnology analyst at William Blair, said of the initial results announced in September.
Lecanemab’s positive results followed a controversy over a different drug developed by Eisai and Biogen, aducanumab. That drug, known by the brand name Aduhelm, was approved by the FDA last year despite conflicting data on its effectiveness. Aduhelm fizzled commercially after Medicare declined to broadly reimburse for it.
“This is an unambiguously positive clinical trial,” said Gil Rabinovici, a neurologist at the University of California at San Francisco, while acknowledging that there is a “potentially serious safety concern that will require a discussion with patients.” Still, he added, “for the first time in over a century, we have modified the course of Alzheimer’s disease, and that is great news for the field and most importantly for patients.”
Lecanemab is designed to work by removing clumps of tiny proteins known as amyloids from the brain, and the study found that patients experienced a greater cumulative benefit the longer they were on the drug. Yet, despite the drug’s early success, some experts remain skeptical that targeting these amyloids is the key to treating Alzheimer’s. This month, Roche announced disappointing results from its anti-amyloid drug.
Matthew Schrag, a neurology professor at Vanderbilt University Medical School, said the lecanemab trial was well-designed and showed strong statistical results on a cognitive measure. But he doubted that the drug would cause a noticeable improvement for many sufferers, and noted that the medication can cause significant side effects.
“I worry any minor benefit may be washed out by the practical difficulties of living with the drug and the substantial risks associated with taking the drug,” he said in an interview.
Eisai and Biogen reported that patients in the trial experienced brain swelling and bleeding, which are known to be complications of anti-amyloid drugs, but the companies said the rates were within expectations. Concerns about the drug’s safety, however, were heightened by the two patient deaths.
On Sunday, Science magazine reported that a patient taking lecanemab died after suffering a stroke and receiving a medication to bust blood clots. That followed a report last month by Stat news that another patient in the trial had died while on a blood-thinner. Both deaths reportedly stemmed from a condition where amyloid binds to blood vessels in the brain and makes them more susceptible to rupture.
Research analysts at investment bank UBS questioned whether the deaths would lead to FDA restrictions for patients taking blood-thinners, which it estimated could make up as many as 20 percent of Alzheimer’s patients.
Libby Holman, a spokeswoman for Eisai, said the patients who died had underlying medical conditions and risks, including being on medications that prevent blood clots, that contributed to their deaths. “It is Eisai’s assessment that the deaths cannot be attributed to lecanemab,” she said, adding that the rates of brain hemorrhage deaths were 0.1 percent for patients in both the placebo and treatment groups.
Despite unknowns about lecanemab’s risk and benefits, it remains a draw for patients suffering from Alzheimer’s eager for any option to slow its degenerative effects and contribute to finding a cure.
Hugh Courtney, a 59-year-old economist diagnosed with early Alzheimer’s, said he feels lucky to have participated in the clinical trial even if he isn’t sure how much he’s benefited.
“It’s hard to tell how much has changed, quite frankly,” he said of the lecanemab infusions he gets about twice a month. Still, he said, “it’s given me a sense of purpose, a concrete way to help.”