Japan’s Eisai has refused to rule out the possibility its Alzheimer’s drug contributed to brain bleeds in two patients who died during clinical trials but insisted its medicine was not responsible for their deaths.
The company said the deaths could not be directly attributed to lecanemab, a drug it is developing with Biogen that slows the rate of cognitive decline in early-stage patients by 27 per cent, according to a late-stage trial.
Both of the patients who died — a 65-year old woman and a man in his 80s — had also taken blood thinning medicines. That prompted Eisai to recommend doctors hold so-called risk-benefit discussions with caregivers and sufferers before prescribing the treatment to those on anticoagulation drugs.
However, Eisai defended the safety of its monoclonal antibody therapy, the first drug to slow progression of Alzheimer’s in a large study trial, which has raised hopes of a new treatment for a disease affecting 50mn people worldwide.
“Our assessment is that these deaths cannot be attributed to lecanemab. Of course, we cannot rule out the possibility that lecanemab might have increased the susceptibility of bleeding risk in the brain,” Ivan Cheung, chief executive of Eisai US, said in an interview ahead of the presentation of detailed trial results on Tuesday.
The results presented at a conference in San Francisco showed 13 out of almost 1,800 participants died during the first 18 months of the trial, but investigators did not attribute any of the fatalities to lecanemab. Seven of the deaths were among trial participants on a placebo rather than the active Alzheimer’s drug.
The two deaths that have caused consternation among investors occurred after the initial 18 months during an extension period, when patients that had been given a placebo were also offered lecanemab. Doctors have long worried that monoclonal antibodies treating Alzheimer’s can cause swelling and bleeding in the brain.
Eisai said one of the patients died of a brain haemorrhage while an autopsy conducted on the second, who also experienced brain bleeding, concluded the cause of death was cardio pulmonary.
“Both of these cases had complicating factors,” said Michael Irizarry, Eisai’s vice-president of clinical research. “Lecanemab does not appear to be the direct cause of death for these. [But] we can’t rule out that there might be a contribution.”
“We do believe that there will need to be a benefit risk discussion regarding the use of lecanemab and people who are on anticoagulation or want to start anticoagulation.”
Serious adverse events occurred in 14 per cent of the participants in the group of patients on lecanemab, compared to 11.3 per cent of those in the placebo group.
Almost one in six participants given lecanemab experienced micro-bleeds in the brain, compared to just under one in ten people on a placebo, according to the study results.
Health experts who reviewed the results of the study, which have been peer reviewed and published in the New England Journal of Medicine, said longer trials were warranted to determine the effectiveness and safety of lecanemab.
Keith Vossel, a professor of neurology at the University of California Los Angeles, said deaths were to be expected during trials where participants tend to be elderly.
He said the fatalities might not stop the drug securing regulatory approval but could affect doctors’ perceptions of how safe the treatment is and whether it should be widely prescribed.
“I personally would not use it hardly at all in patients that have risk factors for bleeding in the brain, like, if they’re on a blood thinner,” said Dr Vossel.