Eli Lilly headquarters in Indianapolis, Indiana, USA, on Wednesday, May 3, 2023. Eli Lilly & Co. stock. rose in early U.S. trading after the experimental Alzheimer's drug slowed the disease's progression in a late-stage trial. clearing the way for the company to apply for US approval.
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A panel of independent advisers to the Food and Drug Administration recommended this on Monday Eli LillyThe Alzheimer's drug donanemab, paving the way for the treatment to receive full approval in the US later this year.
The FDA generally follows the recommendations of its advisory panels, but is not obligated to do so. If approved for use, Eli Lilly's donanemab would become the second Alzheimer's drug of its kind to hit the U.S. market, following another treatment called Leqembi from Biogen and its Japanese partner Eisai.
An approval would expand the now limited treatment options for the more than 6 million Americans who have Alzheimer's disease, the fifth leading cause of death for adults over 65 years old.
In an initial vote, 11 committee members unanimously said that available data on the drug shows it is effective in treating Alzheimer's patients in the early stages of the mind-consuming disease. But several consultants noted that more data is needed on donanemab in black and Hispanic patients, among others.
In a second vote, advisers unanimously said the benefits of Eli Lilly's donanemab outweigh its risks.
“There is a huge unmet medical need here that hopefully can be addressed,” interim committee member Sarah Dolan said at the meeting a meeting on Monday. Dolan is a consultant for the nonprofit Critical Path Institute, which aims to improve the drug development process.
Eli Lilly is “pleased” with the panel's recommendation and looks forward to bringing the treatment to patients, Mark Mintun, group vice president of neuroscience research and development at Eli Lilly, said in a statement.
The recommendation follows challenges Eli Lilly faced in bringing the treatment to market.
The FDA convened a last-minute advisory panel meeting in March to further assess the safety and efficacy of Eli Lilly's drug in late-stage research, just weeks before the agency's deadline to decide on the treatment.
It was another blow to Eli Lilly, which initially expected donanamb to win approval late last year. The FDA also rejected the drug last January, saying there wasn't enough data to greenlight it.
Leqembi and donanemab are milestones in the treatment of Alzheimer's disease after three decades of failed attempts to develop drugs to combat the deadly disease.
Both drugs are monoclonal antibodies that target amyloid plaques in the brain, considered a hallmark of Alzheimer's disease, to slow the progression of the disease in patients in its early stages.
But neither treatment is a cure.
Drugs that target and remove amyloid plaques can also cause swelling and bleeding in the brain in patients, which can be serious and even fatal in some cases. Three patients taking Eli Lilly's drug late in the study died from severe cases of these side effects, called amyloid-related imaging abnormalities, or ARIA.
A host of hurdles have slowed Leqembi's rollout since its approval in July, including the steps needed to diagnose Alzheimer's disease and monitor and handle the weekly infusions required with the drug. Biogen and Eisai indicated in April that they are seeing an increase in adoption.
In a note Sunday, Leerink Partners analyst David Risinger said he expects limited commercial adoption of donanemab compared to Leqembi because Eli Lilly's drug has “more safety risks” and will be less convenient because it is administered once a month via the veins is administered. That is a method known as intravenous infusion.
Leqembi is currently administered via bimonthly infusions, but Biogen expects to launch an injectable version of the drug next year, Risinger noted. He expects donanemab to bring in $500 million in sales by the end of the decade.
How effective is Eli Lilly's Alzheimer's drug?
Eli Lilly's phase three trial in more than 1,700 patients found that donanemab slowed the progression of Alzheimer's disease by 29% after about 18 months compared with a placebo, based on a traditional tool used to measure the severity of dementia to measure.
These results are comparable to those at Leqembi.
Patients in Eli Lilly's phase three trial were required to test positive on a PET scan for amyloid plaque and another protein in the brain called tau, which is thought to be a marker for the severity of Alzheimer's disease. People with no or very low tau levels were not included in the study's primary analysis because researchers thought their disease was less likely to develop during the study.
Eli Lilly's study focused mainly on patients with low to moderate levels of tau, who appeared to benefit more from the treatment than those with high levels of tau.
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Eli Lilly argued that patients must be tested for amyloid plague to qualify for the drug, but not for tau. The company said it tested for tau in the trial to enroll patients whose condition was expected to worsen, making it more likely that the study “clearly established” the drug's effect.
Most advisors agreed that tau testing should not be required to access donanemab as this would likely limit the population that can benefit from the drug.
“From a very practical perspective, I don't think it's wise to have this as a barrier,” said interim committee member Dr. Kathleen Poston, professor of neurology, neurological sciences and neurosurgery at Stanford University, during the meeting on Monday.
Patients taking Eli Lilly's drug in the trial were eligible to switch to a placebo if amyloid levels in their brains fell below a certain threshold. By the end of the trial, 60% of participants were able to stop donanemab treatment.
Dolan said allowing patients to stop the drug once enough amyloid has been cleared could be a “motivating factor” for patients to monitor their infusions and get regular testing.
Risks of brain swelling, bleeding
About 24% of trial participants taking donanemab experienced brain swelling, while 31% experienced brain hemorrhage.
The majority of these ARIA cases were mild to moderate, as 6% of participants with brain swelling and 1% with brain hemorrhage experienced symptoms. These include headache, confusion, dizziness, nausea and in rare cases seizures.
Severe cases occurred in 1.5% of patients with brain swelling and in less than 1% of patients with cerebral hemorrhage.
If donanemab is approved, FDA officials say they expect the drug's label to include a strong warning about the risks of swelling and bleeding in the brain, especially for people with two copies of a gene called ApoE4. They also expect recommendations for MRIs to monitor these side effects in patients, among other strategies.
This corresponds to Leqembi's approval label.
There were 19 deaths among participants taking donanemab, including three attributed to Eli Lilly's drug, within the 18-month trial, according to a final analysis of data by FDA personnel. That compares with 16 deaths in patients who received a placebo, reflecting a smaller imbalance in the number of deaths between people who took donanemab and those who did not.
