Eli Lilly headquarters in Indianapolis, Indiana, U.S., on Wednesday, May 3, 2023. Shares of Eli Lilly & Co. rose in early U.S. trading after its experimental Alzheimer's drug slowed disease progression in a late-stage trial. paving the way for the company to apply for US approval.
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An independent advisory panel to the Food and Drug Administration on Monday recommended Eli LillyDonanemab, an Alzheimer's drug, paves the way for the treatment to receive full approval in the United States later this year.
The FDA typically follows the recommendations of its advisory panels, but is not required to do so. If authorized for use, Eli Lilly's donanemab would become the second Alzheimer's drug of its kind to enter the U.S. market after another treatment called Leqembi from Biogen and its Japanese partner Eisai.
An approval would expand now-limited treatment options for the more than 6 million Americans who suffer from Alzheimer's, the fifth leading cause of death among adults age 65 and older.
In a first vote, 11 committee members unanimously said available data on the drug shows it is effective in treating Alzheimer's patients in the early stages of the mind-wasting disease. But several advisers said more data is needed on donanemab in black and Hispanic patients, among other groups.
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 can hopefully be addressed,” temporary committee member Sarah Dolan said during a meeting Monday. Dolan is a consultant for the nonprofit Critical Path Institute, whose goal is to improve the drug development process.
The recommendation comes after the problems Eli Lilly faced in bringing the treatment to market.
In March, the FDA called a last-minute meeting of an advisory panel to further review the safety and effectiveness of Eli Lilly's drug in a late-stage trial, just weeks before the agency's deadline to rule. about the treatment.
It was another blow for Eli Lilly, which initially expected donanameb to win approval late last year. The FDA also rejected the drug in January last year, saying it did not have enough data to give it the green light.
Leqembi and donanemab are milestones in the treatment of Alzheimer's after three decades of failed efforts to develop drugs that can combat this deadly disease.
Both drugs are monoclonal antibodies that target amyloid plaque in the brain, considered a hallmark of Alzheimer's, to slow the progression of the disease in patients who are in the early stages of the disease.
But none of the treatments are a cure.
Medications that target and remove amyloid plaque can also cause brain swelling and bleeding in patients, which in some cases can be serious and even fatal. Three patients who took Eli Lilly's drug in a late-stage trial died from severe cases of those side effects, called amyloid-related imaging abnormalities, or ARIAs.
A series of obstacles have slowed the launch of Leqembi since its approval in July, including the steps required to diagnose Alzheimer's and monitor and manage the weekly infusions required with the drug. Biogen and Eisai noted in April that they were seeing an increase in adoption.
In a note on Sunday, Leerink Partners analyst David Risinger said he expects limited commercial adoption of donanemab relative to Leqembi because Eli Lilly's drug has “more safety risks” and will be less convenient since it is administered once a month through the veins. That's a method known as intravenous infusion.
Currently, Leqembi is administered via infusions twice a month, but Biogen hopes to launch an injectable version of the drug next year, Risinger said. He expects donanemab to generate $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 Alzheimer's progression by 29% compared to a placebo after about 18 months, based on a traditional tool used to measure the severity of dementia.
These results are comparable to those observed with Leqembi.
Patients in Eli Lilly's phase three trial were required to test positive on a PET scan for amyloid plaque and another brain protein called tau, which is believed to be a marker of the severity of Alzheimer's. People with very low or no tau levels were not included in the main analysis of the trial because researchers thought their disease was less likely to progress during the study.
The Eli Lilly trial focused primarily on patients with low to medium 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 should be tested for amyloid plague to be eligible 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 would “clearly determine” the drug's effect.
Most advisors agreed that tau testing should not be required for access to donanemab because it would likely restrict the population that can benefit from the drug.
“From a very practical perspective, I think it would be unwise to have this as a barrier,” Dr. Kathleen Poston, a temporary committee member and professor of neurology, neurological sciences and neurosurgery at Stanford University, said during the Monday meeting.
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. At the end of the trial, 60% of participants taking donanemab were able to stop treatment.
Dolan said allowing patients to stop the medication when enough amyloid has been removed could be a “motivating factor” for patients to comply with their regular infusions and tests.
Risks of brain inflammation, bleeding.
About 24% of trial participants taking donanemab experienced brain swelling, while 31% experienced brain hemorrhage.
Most of those ARIA cases were mild to moderate, with 6% of participants with brain swelling and 1% with brain hemorrhage experiencing symptoms. They included headache, confusion, dizziness, nausea and, in rare cases, seizures.
Severe cases occurred in 1.5% of patients with brain inflammation and less than 1% with brain hemorrhage.
If donanemab is approved, FDA staff said they hope the drug's label will include a strong “boxed” warning about the risks of brain inflammation and bleeding, 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 is consistent with Leqembi's approval label.
There were 19 deaths in participants taking donanemab, including three attributed to the Eli Lilly drug, within the 18-month trial, according to a final analysis of the data by FDA staff. That compares with 16 deaths in patients who took placebo, reflecting a smaller imbalance in the number of deaths between people who took donanemab and those who did not.
