A month after drugmaker Eisai reported positive, topline phase three data of its Alzheimer’s treatment lecanemab, it has been reported that one of the trial investigators flagged the death of a participating patient after bleeding in the brain – and concluded it might have been related to the drug.
Citing a suspect adverse events report it had obtained, STAT reported that Eisai acknowledged “at least a reasonable possibility lecanemab may have contributed to the” haemorrhage, but ultimately concluded that other factors made it difficult to nail down.
According to Fierce BIOTECH, the patient developed the condition while enrolled in the open-label extension of the phase three trial, and because the phase three trial remains blinded, it’s not known whether he/she previously received lecanemab or placebo.
Eisai pointed to other health factors impacting the patient, including a heart attack and mini stroke-like events. The company also noted that after the heart attack, doctors prescribed the patient an additional blood thinner even after the bleed was discovered.
Nonetheless, STAT says Eisai directed its data and safety monitoring board to check for whether anticoagulants increased the risk of severe side effects. The board found that in fact, yes, a higher share of treated patients on blood thinners did report severe bleeds compared with those not on blood thinners, but the board concluded that this remained a relatively low-risk. The board ultimately did not recommend against including patients on blood thinners.
In a statement to Fierce Biotech, Eisai acknowledged the death, saying: “All of the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.” The company also said that information includes a review of all amyloid-related imaging abnormalities (ARIA) safety data.
In Eisai’s initial data release, the company reported that the symptomatic rate of ARIA-E was 2.8% compared with 0.0% for the lecanamab and placebo groups, respectively, while the symptomatic rate of ARIA-H was 0.7% and 0.2%.
The company told CNN because of patient privacy issues, it could not provide specific information about patients or comment on information from other sources.
In September, Eisai reported preliminary results from the trial that found the treatment slowed the progression of cognitive decline by 27% compared with a placebo.
The company said at the time that it believed that the study results “prove the amyloid hypothesis, in which the abnormal accumulation of (amyloid beta) in the brain is one of the main causes of Alzheimer’s disease”.
Dr Richard Isaacson told CNN in September that this was not proof per se but that the trial was significant. Isaacson is the director of the Alzheimer’s Prevention Clinic at the Centre for Brain Health at Florida Atlantic University’s Schmidt College of Medicine.
“In the past, reducing amyloid in the brain has not always been tied to cognitive improvements or any meaningful clinical improvements. In this study, every endpoint was positive. That’s never happened before.”
The early results showed that nearly 3% of the trial participants who took the drug had a side effect called ARIA-E, swelling in the brain, but no one who took the placebo did.
Eisai sent shockwaves through the pharma world in late September when it posted positive topline phase three data of lecanemab, showing the 27% reduction in clinical decline among patients with early Alzheimer’s disease. It was arguably the most consequential clinical Alzheimer’s data to date.
The company is currently pushing lecanemab through the US Food and Drug Administration’s accelerated approval pathway, with regulators expected to rule by early January. It then plans to submit full approval filings at the FDA and other global regulators by the end of the first quarter of 2023.
Eisai could have a major blockbuster on its hands, though it will heed the lesson learned by its former partner Biogen if it is going to bring in the big bucks.
Last year Biogen nabbed historic FDA approval for its Alzheimer’s drug Aduhelm, which works in a similar way to Eisai's drug, but the promised blockbuster sales never came after it became a major commercial flop amid ongoing safety concerns, deep questions over its efficacy and the decision not to have the drug funded by Medicare.
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