US FDA staff raise no major concerns about Eli Lilly Alzheimer’s drug

The U.S. Food and Drug Administration (FDA) has conducted an analysis of trial data for Eli Lilly’s experimental Alzheimer’s drug donanemab. The analysis, released on Thursday, did not find any major concerns, but it did raise questions about the safety of the treatment for patients in the early stages of the disease.

Donanemab is seen as a potential competitor to Eisai and Biogen’s Leqembi, which received approval in July last year. Both drugs are antibodies designed to eliminate the toxic beta amyloid plaques that accumulate in the brains of individuals with early Alzheimer’s disease.

The FDA will convene an external panel of advisers on Monday to review the staff’s analysis and vote on whether the benefits of donanemab outweigh its risks. While the panel’s recommendations are not binding, the FDA typically follows them.
According to FDA staff, if donanemab is approved, its prescribing label will emphasize certain risks and strategies to manage those risks. These risks include brain swelling and bleeding, particularly in individuals with two copies of the ApoE4 gene.

Additionally, FDA staff reviewers stated that post-approval requirements may include expedited reporting of any deaths in ongoing studies of the drug and the collection of data on side effects through a patient registry.

Several analysts predict that donanemab will be approved. This drug, along with Leqembi, represents a new era in Alzheimer’s treatment, as they are designed to slow down the progression of the disease. This marks a significant development after decades of unsuccessful attempts to find effective drugs for this debilitating condition.

In a large-scale clinical trial, donanemab, administered via monthly infusion, demonstrated a 29% overall reduction in the progression of memory and cognitive decline. This result is comparable to the 27% slowing observed with Leqembi.
According to RBC analyst Brian Abrahams, the agency’s overall comments may slightly favor Leqembi due to its fewer adverse side effects. However, the FDA seems inclined to approve Lilly’s drug.

In the trial, 24% of participants taking donanemab experienced brain swelling, while 31% experienced brain bleeding. The majority of these cases were mild, with 6% experiencing symptoms of brain swelling and 1% experiencing symptoms of brain bleeding.

Serious cases of brain swelling occurred in 1.5% of patients, while serious cases of brain bleeding occurred in 0.4% of patients.

The FDA requested a broader analysis of deaths, including those who dropped out of the trial. After considering this additional information, there were 19 deaths among participants on donanemab, with three attributed to the treatment. In comparison, there were 16 deaths among patients on placebo, indicating a smaller difference in the number of deaths between the two groups.
In a late-stage study conducted by Eisai and Biogen, it was found that 12.6% of participants who took Leqembi experienced brain swelling, while 17.3% experienced brain bleeding.

Following the approval of Leqembi, the FDA issued a strong warning, known as a “boxed” warning, regarding the potential risk of dangerous brain swelling and bleeding. The FDA also recommended regular MRIs or brain scans to monitor the safety of patients taking Leqembi.

Stifel analyst Paul Matteis commented on the situation, noting that the label for Leqembi will be of particular interest, as it remains to be seen whether longer-term MRI scans will be recommended for patients compared to the three recommended after starting treatment with the drug donanemab.

In contrast to the trial conducted by Eisai and Biogen, Lilly, another pharmaceutical company, measured levels of a different protein called tau, which is associated with Alzheimer’s disease and indicates brain cell death. In their submission to the FDA, Lilly argued that tau imaging is not necessary to determine which patients will benefit from the drug.
In the donanemab trial, participants were allowed to discontinue treatment once brain imaging indicated the clearance of amyloid plaque. However, FDA staff expressed concerns about the duration of the treatment’s effectiveness.

According to the Alzheimer’s Association, over 6 million Americans are affected by various forms of memory loss conditions.

Reported by Bhanvi Satija in Bengaluru, Deena Beasley in Los Angeles, and Julie Steenhuysen in Chicago. Edited by Bill Berkrot.

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