Eli Lilly Claims Kisunla Brain Swelling Side Effects Can Be Reduced With Modified Dosing Schedule

Findings come amid continuing concerns drug maker failed to inform clinical trial subjects that their genetics could increase the risk of brain swelling from Kisunla.

To reduce the risk of brain swelling that may result from side effects of Kisunla, Eli Lilly indicates that it is altering the dosing plan for its recently introduced Alzheimer’s disease drug.

Kisunla (donanemab) was approved by the U.S. Food and Drug Administration (FDA) in July 2024, as part of a new generation of Alzheimer’s disease and dementia medications, which work by affecting proteins that form plaque in the brain, known as beta-amyloids. It is part of a new class of treatments, known as anti-amyloid drugs, that also include the direct competitors Leqembi and Aduhelm, which were developed by Eisai and Biogen, respectively.

These new Alzheimer’s drugs do not stop cognitive decline or reverse brain damage, but do remove the plaques in the brain, and are designed to slow disease progression. However, concerns have emerged about potentially serious side effects Kisunla, Leqembi and Aduhelm may have on the brain, including a potential risk of brain swelling, brain bleeds and brain shrinkage.

The most recent clinical trials for Kisunla, known as Trailblazer-Alz, found that nearly a quarter of patients taking the standard dosing regimen experienced brain swelling side effects. That dosing schedule requires patients to receive three Kisunla infusions of 700 mg over a period of four weeks. This is followed by 1,400 mg doses given over the same time interval.

However, Eli Lilly issued a press release on October 29, indicating that an alternate dosing schedule that starts with a lower dose appears to reduce the chance of brain swelling.

The alternate dosing plan calls for a first injection of just 350 mg, with follow-up doses being given every four weeks, increasing to 700 mg, 1,050 mg, and 1,400 mg, with each dose. As a result, the rate of brain swelling from Kisunla dropped to 14% among those patients.

Alzheimer’s Disease Drug Approval Concerns

The FDA has faced substantial criticism in recent years over its approval of Kisunla, Leqembi and Aduhelm, as critics indicate there were too many questions about the safety and effectiveness of the drugs during their clinical trials.

A recent New York Times report indicates that Eli Lilly and Eisai both failed to disclose the risk of brain problems from the Alzheimer’s drugs to clinical trial test subjects, including indications that patients with certain genetic profiles may face a greater risk of brain bleeds and brain swelling. Bioethicists have called this process “ethically fraught.”

In addition, a study published last year by former FDA scientific advisors indicated an agency history of bias toward approving new drugs, particularly those involving Alzheimer’s disease treatments.

The study found that federal regulators almost always follow the recommendations of its advisory committees when the members indicate a drug should be approved. However, when independent advisory panels recommend rejecting a proposed new treatment, the agency only follows that advice about two-thirds of the time.

Scientific advisory committees are designed to offer advice on approving or rejecting new drugs. While the FDA is not required to follow their recommendations, the findings are supposed to guide regulatory decisions.

Following a review of the Alzheimer’s drug Adulhelm, the FDA’s scientific advisory committee voted against the approval, calling it reckless, since there was no evidence indicating the drug was beneficial to patients. As a result, two members of the committee resigned in protest, while a Congressional report indicated the FDA has a close relationship with Biogen, the maker of Aduhelm.