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 final-stage trial . This paved 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 Monday Eli LillyThe Alzheimer’s drug donanemab was developed, paving the way for full approval of the treatment in the US later this year.
The FDA generally follows the recommendations of its advisory committees, but is not required to do so. If approved, Eli Lilly’s donanemab would be the second Alzheimer’s drug of its kind currently on the U.S. market, following another drug called Leqembi from Biogen and its Japanese partner Eisai.
Approval would expand now-limited treatment options for the more than 6 million Americans suffering from Alzheimer’s disease, the fifth leading cause of death in adults over 65.
In an initial vote, 11 committee members said unanimously that available data on the drug shows it is effective in treating Alzheimer’s patients in the early stages of the mind-altering disease. However, several consultants noted that more data on donanemab is needed in black and Hispanic patients, among others.
In a second vote, advisers agreed that the benefits of Eli Lilly’s donanemab outweighed the risks.
“There is a huge unmet medical need here that hopefully can be addressed,” interim committee member Sarah Dolan said during a meeting Monday. Dolan is an advisor to the non-profit organization 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 difficulties Eli Lilly faced in bringing the treatment to market.
The FDA convened a last-minute advisory panel meeting in March 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 decide on the treatment.
It was another blow to Eli Lilly, which initially expected donananameb to win approval late last year. The FDA also rejected the drug in January last year, saying there wasn’t enough data to give it the green light.
The FDA appears to be considering donanemab more cautiously after receiving the polarizing approval of the ill-fated Alzheimer’s drug Aduhelm from Biogen and Eisai. The authority granted accelerated approval to this treatment despite a negative recommendation from an advisory committee.
Biogen and Eisai have since discontinued the drug.
Leqembi and donanemab are milestones in the treatment of Alzheimer’s after three decades of failed efforts to develop drugs to combat the deadly disease.
Both drugs are monoclonal antibodies that target amyloid plaque in the brain, considered a hallmark of Alzheimer’s disease, to slow the progression of the disease in early-stage patients.
But none of the treatments are a cure.
Medications that target and eliminate amyloid plaques can also cause patients to experience brain swelling and bleeding, which can be serious and even fatal in some cases. Three patients who took Eli Lilly’s drug in a late-stage study died from severe cases of these side effects, called amyloid-related imaging abnormalities, or ARIA.
A variety of hurdles have slowed the rollout of Leqembi since its approval in July, including the steps required to diagnose Alzheimer’s and monitor and manage required weekly infusions of the drug. Biogen and Eisai signaled in April that acceptance was increasing.
In a note Sunday, Leerink Partners analyst David Risinger said he expects limited commercial acceptance of donanemab compared to Leqembi because Eli Lilly’s drug poses “more safety risks” and will be less practical as it administered through the veins once a month. This is a method known as intravenous infusion.
Leqembi is currently administered through twice-monthly infusions, but Biogen expects to bring an injectable version of the drug to market 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 3 trial in more than 1,700 patients found that donanemab slowed the progression of Alzheimer’s disease by 29% compared to a placebo after about 18 months, based on a traditional tool for measuring dementia severity.
These results are comparable to those of Leqembi.
Patients in Eli Lilly’s Phase 3 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 of the severity of Alzheimer’s disease. People with no or very low levels of tau were not included in the study’s primary analysis because researchers believed their disease would be less likely to progress during the study.
Eli Lilly’s study focused primarily on patients with low to moderate tau levels, who appeared to benefit more from the treatment than patients with high tau levels.
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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 study to include patients whose condition was expected to worsen, making it more likely for the study to “unambiguously determine” the drug’s effect.
Most advisers agreed that tau testing should not be required for access to donanemab because it would likely limit the population that can benefit from the drug.
“From a very practical point of view, I think it wouldn’t be a wise thing to use this as a barrier,” said Dr. Interim committee member Kathleen Poston, professor of neurology, neurological sciences and neurosurgery at Stanford University, during the meeting Monday.
Patients taking Eli Lilly’s drug in the study were able to switch to a placebo if amyloid levels in their brain fell below a certain threshold. At the end of the study, 60% of participants receiving donanemab were able to discontinue treatment.
Dolan said allowing patients to stop taking the drug when enough amyloid has been cleared could be a “motivating factor” for patients to comply with their infusions and regular testing.
Risk of brain swelling and bleeding
About 24% of study participants who took donanemab experienced brain swelling, while 31% experienced brain bleeding.
The majority of these ARIA cases were mild to moderate, as 6% of participants experienced brain swelling and 1% of participants experienced cerebral hemorrhage. These included headaches, confusion, dizziness, nausea and, in rare cases, seizures.
Serious cases occurred in 1.5% of patients with cerebral swelling and in less than 1% with cerebral hemorrhage.
If donanemab is approved, FDA officials expect the drug’s label will contain a clear warning about the risks of brain swelling and bleeding, particularly for people with two copies of a gene called ApoE4. Among other things, they also expect recommendations for MRIs to monitor these side effects in patients.
This is consistent with Leqembi’s approval label.
According to a final data analysis by FDA staff, there were 19 deaths in participants taking donanemab during the 18-month study, including the three attributable to Eli Lilly’s drug. This compares with 16 deaths in patients taking placebo, reflecting a smaller imbalance in the number of deaths between people who took donanemab and those who did not.
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2024-06-10 21:08:08
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