A third patient has died while being treated with an experimental Alzheimer’s drug that doctors hope will herald the “beginning of the end” for the disease.
The unnamed 79-year-old woman from Florida suffered severe swelling and bleeding in her brain after receiving the treatment for more than 18 months. She was hospitalized with seizures in mid-September and died five days later.
The patient was in the extension phase of phase 3 studies for the antibody drug lecanemab, which is being supported by the biotech company Eisai. The treatment works by removing amyloid beta proteins from the brain, which are thought to cause Alzheimer’s.
This is the latest setback for trials of the drug, which found it could slow the progression of Alzheimer’s disease by 27 percent over 18 months in the core part of the Phase 3 trial. The Food and Drug Administration (FDA) is expected to decide within the next month whether to approve the drug for use in the United States.
The scans above show the woman’s brain before treatment with the antibody (left) and after (right). Her brain swelled up during treatment and showed signs of bleeding
The latest death in the trial was revealed in Science magazine. It is associated with bleeding and swelling in the brain.
Two more deaths follow during the extension phase, including a man in his late 80s who died of a brain hemorrhage in June and the death of a 65-year-old Illinois woman.
Experts at the Tokyo, Japan-based biotechnology company said the deaths were likely due to other factors.
They linked the man’s death to a blood thinner he was also using and said the woman’s death was due to other medical problems.
The company has declined to comment on the recent death, citing privacy concerns.
A spokesperson said: “All serious events, including fatalities, will be reported to Eisai and will be considered in our review of the study.
Everything you need to know about the Alzheimer’s drug lecanemab
what does it do
Lecanemab is a drug that is injected every two weeks into patients with early-stage Alzheimer’s disease.
The antibody treatment, developed by Japanese and US pharmaceutical giants Eisai and Biogen, fights the build-up of plaque in the brain thought to be behind Alzheimer’s.
What have tests shown?
The phase III study of lecanemab evaluated the drug’s ability to reduce cognitive and functional decline in 1,795 patients with early-stage Alzheimer’s disease.
Half of the participants received 10 mg/kg of the drug every two weeks, while the others received a placebo drug.
The researchers measured the participants’ memory, judgment, problem solving, and judgment before they started taking the drug or placebo and again 18 months later.
The results showed that those given lecanemab worsened 27 percent less than those given the sham treatment.
The lecanemab group also experienced a slower build-up of amyloid levels in the brain, scans showed.
Is the drug dangerous?
In addition to promising results, clinical studies have also revealed safety concerns.
Brain swelling and microbleeds were seen in 21.3 percent in the lecanemab group and 9.3 percent in the placebo group.
According to the pharmaceutical giant, the numbers are in the expected range.
And a patient in the US reportedly died while taking lecanemab during clinical trials after suffering a brain hemorrhage.
However, Eisai and Biogen noted that all available safety information shows that the therapy is not associated with an increased risk of death.
How close is it to launch?
The drugmakers are seeking approval for lecanemab from the U.S. Food and Drug Administration, with a decision expected in early January.
The companies say they will also submit their findings to regulators in Japan and Europe by April 2023.
However, the watchdogs then have to assess whether the drug is safe and effective before making a decision, leaving it unclear when the treatment could be introduced.
How does it differ from the similar drug Aduhelm?
Both Aduhelm and lecanemab — both made by Eisai and Biogen — are antibodies designed to remove amyloid deposits.
However, lecanemab targets amyloid that hasn’t yet clumped together, while Aduhelm removes amyloid plaques that have built up in the brain.
The approval of Aduhelm was a rare bright spot for Alzheimer’s patients, but critics have warned of the drug’s disappointing results and highlighted its risks.
“This information will be provided to the FDA and other regulatory agencies and independent review panels for the study.”
A total of 13 fatalities were recorded in the core trail from 1,800 participants.
It wasn’t clear if these were related to the drug or other factors, but all participants had early-stage Alzheimer’s and had a median age of 71 years.
People with Alzheimer’s can live for several years after the first symptoms appear.
According to the Mayo Clinic, most patients live three to 11 years after diagnosis.
Patients were initially recruited for the Phase 3 core studies, which lasted 18 months, before moving into the six-week extension phase, during which they received doses of the drug every two weeks.
The last patient to die in the study had progressed through the core phase without issue and was then transferred to the extension phase.
But her family, who revealed the case anonymously, said she became so tired after the first injection that she stayed in bed for two days – just to go to the bathroom or eat a snack.
Two weeks later she received the second infusion. She suffered from severe headaches, had trouble completing sentences, and was confused.
In mid-September, she apparently suffered a stroke in a restaurant.
The woman was taken to the hospital, where she suffered from seizures. They were so violent that she began beating her arms and legs – which required shackles for her own safety.
The patient began to suffer from multiorgan failure and pneumonia. She died five days later.
Doctors reviewing the case said it was likely lecanemab was behind the death, noting the patient had no underlying medical conditions.
When she was moved into extension, a brain scan showed evidence of some microbleeds, although not severe enough to rule them out.
dr Ellis van Etten, a neuroscientist at Leiden University in Germany, told Science, “The brain swelling and the microbleeds … could be a serious side effect of the study medication.” He said this should be evaluated by investigators.
Lecanemab is one of several experimental Alzheimer’s drugs that target amyloid beta proteins that build up in the brains of people with the disease.
Many scientists argue that this deposit is responsible for the disease, although deposits of the protein can also be seen in the brains of healthy people.
The amyloid-seeking antibodies help remove the proteins but can cause brain swelling and bleeding in the process.
This is a condition medically known as amyloid-related imaging abnormalities (ARIA) because it’s diagnosed through brain scans.
Lecanemab targets two types of amyloid beta plaques.
About half of Alzheimer’s patients also have cerebral amyloid angiopathy CAA, in which amyloid beta plaques replace muscle in the walls of blood vessels.
When these are removed by antibodies, the blood vessels can become weakened and inflamed, increasing the risk of them rupturing.
The FDA is expected to decide next month whether the treatment can be used in the US, while the European Medicines Agency – Europe’s leading drug regulator – is expected to issue an opinion later in 2023.