Eisai Never Told Patients in Leqembi Clinical Trials They Faced Higher Risk of Brain Bleeds: NYT

Scientists and health experts call the Leqembi clinical trials “ethically fraught,” after drugmaker failed to inform test subjects that they had genetic markers that may make them more susceptible to side effects.

A new investigative report claims that the manufacturer of a new generation Alzheimer’s disease drug failed to disclose safety information needed to allow patients to provide fully informed consent during clinical trials for Leqembi, leading to hundreds of serious side effects and some deaths.

According to a New York Times investigative report, drug maker Eisai decided not to tell patients the drug posed a serious risk to some volunteers who had a specific gene, in order to quickly get through the trials and the approval process. As a result, it appears that a number of Leqembi patients suffered severe brain bleeds, brain swelling and some died.

The findings were published on Wednesday, as part of an investigation into clinical trials for Alzheimer’s disease drugs introduced by major pharmaceutical companies in recent years.

Drugs like Leqembi are meant to work by reducing a protein called beta-amyloid that forms plaque in the brains of patients with Alzheimer’s disease.

While the drugs do remove the plaques, they are not designed to stop cognitive decline or reverse brain damage. Patients continue to suffer from reduced cognitive function and in many cases, they also suffer from health side effects caused by the drugs themselves.

An Australian study in April 2023 warned Leqembi and similar Alzheimer’s drugs like Aduhelm, may even speed up the progression of dementia by causing brain shrinking.

Leqembi Clinical Trial Secrecy

The New York Times investigation concluded that Eisai recruited volunteers for the Leqembi clinical trial, telling them that they would undergo genetic testing to determine if they carried a specific gene making them prone to developing Alzheimer’s disease.

In their recruiting efforts, Eisai reportedly indicated the same gene would also increase the volunteer’s risk of brain bleeds or swelling if they took the drug. However, the investigators say Eisai kept the results of the genetic tests secret and did not tell the patients, a tactic that ethicists say violates informed consent rules.

The secrecy provisions were not previously reported during drug trial reviews, or when the drug was approved by the U.S. Food and Drug Administration (FDA) to enter the U.S. market, according to the report.

The provision only came to light during the New York Times’ investigation, after journalists reviewed data from clinical trials, patient records, and injury reports, as well as conducted interviews with researchers, neurologists, trial participants, families of Alzheimer’s patients, and FDA officials. Bioethicists said the secrecy provision was “ethically fraught.”

More than 100 volunteers who were not given the results of their genetic tests suffered brain bleeding and swelling, the data suggests. Some suffered serious and life-threatening symptoms, and several died.

The report indicates one participant took only three doses of the drug and died, after experiencing 51 brain bleeds. An autopsy linked the death directly to side effects of Leqembi.

Data from the drug trials also suggested the benefits of Leqembi were modest, the investigation states. Patients experienced a slowing of cognitive decline by a few months, but ultimately the drug did not prevent a complete decline.

The lack of more significant results from Leqembi has some researchers thinking the dominant theory of Alzheimer’s being caused by plaque in the brain may be incorrect.

Leqembi FDA Approval

Despite lackluster clinical trial results, the FDA granted approval of Leqembi for the treatment of Alzheimer’s in 2023, determining the benefits outweighed the risks.

In July 2024, the FDA approved another Alzheimer’s drug similar to Leqembi, which also removes plaques from the brain and is marketed under the brand name Kisunla. However, the New York Times report suggests that the manufacturer of that drug, Eli Lily, also failed to disclose the genetic profile and risk to study volunteers in their original clinical study. As a result, the report indicates that dozens of participants experienced what Eli Lily classified as “severe” brain bleeds.

In new clinical studies, Eli Lily began giving volunteers the option to learn their test results before entering the Kisunla trial.

European Union drug regulators recommended against approving Leqembi in July, and earlier this month Australia declined to approve the drug. Both said the temporary delay of cognitive decline, by five months at most, did not outweigh the risks of Leqembi side effects.

FDA Bias Toward Approving New Drugs

The FDA has a history of bias toward approving new drugs, according to a study by former FDA advisors. This has become a controversial topic in recent years, particularly involving Alzheimer’s disease treatments.

A scientific advisory committee only offers advice on approving or rejecting new drugs. The FDA is not required to follow their recommendations, but the former advisors’ study indicated the agency almost always follows those recommendations when advisors call for a drug’s approval. However, it only follows recommendations for rejecting new drugs about two-thirds of the time.

The agency came under fire after it approved the Alzheimer’s disease drug Aduhelm in 2021, when the advisory committee voted against approval. The committee called the approval reckless, since there was no evidence indicating it was beneficial to patients.

Two members of the committee resigned in protest of the Aduhelm approval, and a Congressional report indicated the FDA has a close relationship with the drug maker, Biogen.