A report published Wednesday in The BMJ questioned the safety and effectiveness of the Alzheimer’s disease drug Kisunla (donanemab).
Jeanne Lenzer and Shannon Brownlee, independent journalists who published the report, expressed concerns about deaths in people taking the drug as well as the financial ties of drug makers on the panel that approved the medication.
The anti-amyloid drug developed by Eli Lilly provides antibodies targeting the protein thought to cause Alzheimer’s disease.
The Food and Drug Administration denied the drug approval in January 2023, citing missing data and safety concerns. The agency noted a higher rate of treatment discontinuation because of adverse events such as brain hemorrhage and swelling in patients taking the medication compared with placebo. There was an imbalance in overall deaths, the FDA had said. Specifically, 2.7% of people in the group taking donanemab and 1.4% in the placebo group died. The drug was later approved in July this year.
After the FDA’s denial, Lilly acknowledged three deaths among patients taking donanemab, and then hired an outside company to search publicly available records and databases to find the missing data. That information included two additional deaths among those taking donanemab and five deaths in those on the placebo, narrowing the imbalance, according to the FDA.
In the new report, Steven Goodman, an expert in clinical trial design at Stanford University, said scientists can’t assess the reliability of the new data without more details of the outside company’s methods. Lilly refused to name the outside party, the authors noted.
“There was also no information on health outcomes in those patients other than death, nor the causes of the deaths,” he says, adding that the “failure to formally follow patients who stopped treatment was a significant design flaw, particularly when that discontinuation was partly due to adverse drug effects.”
Seven of the eight doctors appointed by the FDA to review donanemab received direct payments from drug companies, the authors said. Three of them had monetary ties to Lilly, and two had ties to Roche (Lilly’s development partner in creating an Alzheimer’s disease blood test). In addition, two others have patents on amyloid antibodies, and the eighth doctor had research funding from Janssen for another Alzheimer’s drug.
Lilly said donanemab slowed progression of Alzheimer’s by 22%, but promotes it as slowing decline by 35%.
“That is a misleading statement,” Alberto J. Espay, a neurologist and specialist in clinical epidemiology and healthcare research at the University of Cincinnati, was quoted as saying in the BMJ report. “That’s a relative difference that transforms a very tiny absolute difference into a number that seems impressive.”
