By Bhanvi Satija and Julie Steenhuysen
(Reuters) – An FDA analysis of trial data for Eli Lilly’s experimental Alzheimer’s drug donanemab released on Thursday revealed no red flags, but raised questions about safety of the treatment for patients with early-stage disease.
The drug is a potential rival to Eisai and Biogen’s Leqembi, which won approval last July.
Both treatments are antibodies designed to remove toxic beta amyloid plaques from the brains of people with early Alzheimer’s disease.
An outside panel of FDA advisers will consider the staff’s view during a meeting on Monday in which they will vote on whether the drug’s benefits outweigh its risks, according to documents published on the agency’s website. The panel’s recommendations are non-binding but typically followed by the U.S. Food and Drug Administration.
If donanemab is approved, FDA staff said they expect its prescribing label to highlight several risks and strategies to mitigate those risks, which include brain swelling and bleeding, especially in people with two copies of a gene called ApoE4.
Post-approval requirements that may also be requested include expedited reporting of any deaths in ongoing studies of the drug and collection of data about side effects through a patient registry, FDA staff reviewers added.
At least two analysts said they expect donanemab will be approved.
Drugs like donanemab and Leqembi, which are designed to slow disease progression, represent a new era in the treatment of Alzheimer’s, after three decades of failed attempts to find drugs to fight the fatal mind-wasting disease.
In a large clinical trial, donanemab, given by infusion once a month, slowed progression of memory and thinking problems by 29% overall, roughly comparable to the 27% slowing seen with Leqembi.
RBC analyst Brian Abrahams said in a research note that overall, the agency’s comments may slightly favor Leqembi due to fewer adverse side effects, but with the FDA appearing inclined to approve Lilly’s drug.
Brain swelling occurred in 24% and brain bleeding in 31% of trial participants taking donanemab. Most cases were mild, with 6% of participants with brain swelling and 1% with brain bleeding experiencing symptoms.
Serious cases occurred in 1.5% of patients with brain swelling and 0.4% with bleeding in the brain.
The FDA asked Lilly for a wider analysis of deaths, including of people who had dropped out of the trial. With the addition of that information, there were 19 deaths in participants on donanemab – three attributed to the treatment – and 16 deaths in patients on placebo, reflecting a smaller imbalance in the number of deaths between the groups.
In Eisai and Biogen’s late-stage study, 12.6% of participants taking Leqembi experienced brain swelling and 17.3% brain bleeding.
With its approval of Leqembi, the FDA issued its strongest “boxed” warning about the risk of potentially dangerous brain swelling and bleeding. It also recommended a series of MRIs or brain scans to monitor Leqembi patients for safety.
“The most interesting wrinkle here will come with the label, and whether MRIs (brain scans) are recommended for longer,” for donanemab than the three recommended after starting Leqembi treatment, said Stifel analyst Paul Matteis.
Unlike Eisai and Biogen’s trial, Lilly measured levels of another Alzheimer’s-related protein called tau – an indicator of brain cell death – to help group patients in the study. In documents submitted to the FDA, Lilly argued that tau imaging is not needed to determine who will benefit from the drug.
Participants in the donanemab trial could stop treatment as soon as brain imaging showed the amyloid plaque was cleared, but FDA staff raised questions about how long the treatment benefit would last.
More than 6 million Americans have some form of the memory-robbing condition, according to the Alzheimer’s Association.
(Reporting by Bhanvi Satija in Bengaluru, Deena Beasley in Los Angeles and Julie Steenhuysen in Chicago; Editing by Bill Berkrot)
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