Nov. 30, 2022 -- Widely anticipated data from a phase 3 trial of a new Alzheimer’s disease treatment suggests the drug "modestly" relieved cognitive problems in patients early into the disease — but at a cost.
In the trial, adverse events among patients taking the drug, lecanemab, were common compared with placebo, including leaking blood vessels ; and a news report this week linked a second death to the drug.
Moving forward, "longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer's disease," Christopher H. van Dyck, MD, of the Yale School of Medicine in New Haven, CT, and colleagues write.
The full trial findings were presented at the 15th Clinical Trials on Alzheimer's Disease conference, and were also published Nov. 29 in the New England Journal of Medicine.
The phase 3 trial of lecanemab has been closely watched in Alzheimer’s circles, especially considering positive early data released in September, reported by Medscape Medical News at that time.
The FDA is expected to decide whether to approve the drug in January. The agency has approved only one other similar treatment, the highly controversial and expensive aducanumab (Aduhelm).
For the new 18-month, randomized, double-blind trial, researchers enrolled 1,795 patients ages 50 to 90 with early Alzheimer’s.. All were randomly assigned to receive either a placebo or intravenous lecanemab.
The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia.
Those on the experimental drug scored 27% better on a Alzheimer’s rating scale compared to those on the placebo.
The study authors did not speculate about how this difference would affect the day-to-day life of patients who took the drug, although it does refer to "modestly less decline" of cognition/function in the lecanemab group.
Concerning Adverse Event Data
With respect to adverse events, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, the journal Science reported Nov. 27 that a 65-year-old woman who was taking the drug as part of a clinical trial "recently died from a massive brain hemorrhage that some researchers link to the drug."
The woman, the second person "whose death was linked to lecanemab," died after suffering a stroke. Science summarized a case report as saying that the drug "contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels."
Eisai, which sponsored the new trial, told Science that "all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause."
In separate interviews with Medscape Medical News, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.
Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School
and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining what are known as anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.
However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive due to the large investment needed for research, he added, and patients will have to undergo costly testing such as PET scans and spinal taps.
Howard Fillit, MD, co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and had what he called a “modest” effect on cognition.
However, the drugmaker will need to explore the adverse effects, he said, especially in patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal -- fully reversing cognitive decline.
Rave Reviews from the Alzheimer's Association
In a statement, the Alzheimer’s Association raved about lecanemab and declared the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease…,” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”
The association, which is also a staunch supporter of aducanumab, called on the Centers for Medicare and Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the 2 reported deaths.