Outside advisers to the U.S. Food and Drug Administration on Monday voted unanimously that the benefits of Eli Lilly’s LLY.N experimental Alzheimer’s treatment donanemab outweighed its risks, and agreed that trial data showed it was effective in patients with an early stage of the memory-robbing disease.
The vote clears the way for a final FDA decision on the treatment, which initially had been expected earlier this year before the agency called for the meeting so its independent panel of experts could weigh in.
“We really are pleased that the advisory committee recognized donanemab’s strong positive benefit risk,” Dawn Brooks, Lilly’s development leader for donanemab, said in an interview after the vote.
Now with the panel’s unanimous support, the company looks forward to the FDA finishing its review, she said.
The agency is not obligated to follow the recommendations of its outside advisers, but typically does so.
In its discussion, the FDA had asked the panel to consider some unique aspects of Lilly’s trial, which differed significantly from the trial design of Eisai 4523.T and Biogen BIIB.O Leqembi, which won U.S. approval after going through a similar advisory committee meeting.
Both drugs are designed to remove toxic beta amyloid plaques from the brains of people with early Alzheimer’s disease.
The antibody treatments, which succeeded in slowing disease progression in clinical trials, follow three decades of failed attempts to find drugs to fight the fatal mind-wasting disease.
A key difference in trial design for the two treatments is that Lilly measured levels of a second Alzheimer’s-related protein called tau associated with brain cell death to select patients most likely to show a benefit within the study’s 76-week trial period.
As a result, Lilly excluded patients with very low or no levels of tau from the pivotal trial, but they did a separate analysis in this group from another fairly large study to see if the drug resulted in underlying changes.
Several panelists noted that that data was likely suggestive of a treatment benefit.
Panelists also largely agreed that testing for tau should not be required before treatment, noting that such testing was not widely available and could reduce access to rural or underserved populations.
Several panel members noted there were elevated safety issues for people who have two copies of the APOE4 gene that is associated with a higher risk of Alzheimer’s. They suggested that doctors prescribing the drug need to be educated on the heightened risk and discuss that with patients.
In Lilly’s 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.
Brain swelling and bleeding – a known risk for this class of drugs – occurred in 24% and 31%, respectively for those taking donanemab and three patients died.
In Eisai and Biogen’s late-stage study, 12.6% of participants taking Leqembi experienced brain swelling and 17.3% brain bleeding.
Leqembi was approved with the agency’s strongest “boxed” warning about the risk of potentially dangerous brain swelling and bleeding that applies to all drugs in the class.
Several panel members commended Lilly’s innovative trial design, which allowed participants to stop treatment as soon as brain imaging showed the amyloid plaque was cleared, but they said it could make the treatment harder for doctors to know when to withdraw treatment, and when to restart it if needed.
Lilly said it is planning trials to test the treatment in patients genetically predisposed to develop Alzheimer’s, including people with Down syndrome.
Jefferies analyst Michael Yee said in a note to clients that the vote “sets up an eventual FDA approval,” adding that having two players on the market would be a good thing longer-term.
Shares of the Indianapolis drugmaker closed up 1.8% at $865.
—Reporting by Bhanvi Satija in Bengaluru and Julie Steenhuysen in Chicago; Editing by Caroline Humer and Bill Berkrot
