Eli Lilly and Company is headquartered in Indianapolis, Indiana, United States, on Wednesday, May 3, 2023. Slowed the progression of the disease, paving the way for the company to apply for U.S. approval.
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An independent advisory panel to the U.S. Food and Drug Administration recommended on Monday Eli Lilly and CompanyAlzheimer’s drug donanemab paves the way for full U.S. approval of the treatment later this year.
The FDA generally follows the recommendations of its advisory panels, but is not required to do so. If approved for use, Eli Lilly’s donanemab would be the second of its kind to enter the U.S. market, following another treatment called Leqembi made by Biogen and its Japanese partner Eisai. Alzheimer’s disease drugs.
If approved, it would expand currently limited treatment options 6000000 Americans with Alzheimer’s disease fifth leading cause of death Suitable for adults aged 65+.
In the first vote, the 11 committee members unanimously said existing data on the drug showed it could be effective in treating patients with early-stage Alzheimer’s disease. But several consultants noted that more data on donanezumab is needed in black and Hispanic patients, as well as other groups.
In a second vote, advisers unanimously said the benefits of Eli Lilly’s donanezumab outweighed its risks.
“There is a huge unmet medical need here that hopefully will be addressed,” interim committee member Sarah Dolan said during the meeting. a meeting on Monday. Dolan is an advisor to the Critical Path Institute, a nonprofit organization that seeks to improve the drug development process.
The recommendation comes after Eli Lilly faced obstacles in bringing the therapy to market.
In March, the FDA convened a last-minute advisory panel meeting to further review the safety and effectiveness of Eli Lilly’s drug in late-stage trials, just weeks before the agency’s deadline to rule on the treatment.
It’s another blow for Eli Lilly, which originally expected to get approval for dolemeib late last year. The FDA also rejected the drug last January, saying there was insufficient data to approve it.
Leqembi and donanemab are milestones in treating Alzheimer’s disease, after three decades of failed efforts 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, to slow the progression of the disease in patients in the early stages.
But neither treatment offers a cure.
Drugs that target and remove amyloid plaques can also cause brain swelling and bleeding in patients, which can be serious or even fatal in some cases. Three patients taking Eli Lilly’s drug in a late-stage trial died from these serious side effects, known as amyloid-related imaging abnormalities (ARIA).
A series of hurdles have hampered Leqembi’s rollout since its approval in July, including the steps required to diagnose Alzheimer’s disease and monitor and manage the weekly infusions the drug requires. Biogen and Eisai said in April that their adoption rates were rising.
Leerink Partners analyst David Risinger said in a report on Sunday that he expects donanemab to have limited commercial use compared with Leqembi because Eli Lilly’s drug has “more safety responsibilities” and due to the monthly intravenous It’s a one-time injection, so it’s not very convenient. This is a method called intravenous infusion.
Risinger noted that Leqembi is currently administered as a twice-monthly infusion, but Biogen expects to launch an injectable version of the drug next year. He expects donanemab sales to reach $500 million by the end of the decade.
How effective is Eli Lilly’s Alzheimer’s drug?
Eli Lilly’s Phase 3 trial of more than 1,700 patients found donanemab slowed the progression of Alzheimer’s disease after about 18 months compared with placebo, based on traditional tools used to measure dementia severity 29%.
These results are comparable to those of Leqembi.
Patients in Eli Lilly’s Phase 3 trial need to have PET scans that detect amyloid plaques and another protein in the brain called tau, which is considered a marker of Alzheimer’s disease severity. People with absent or very low tau levels were not included in the trial’s main analysis because researchers believed their disease was less likely to progress during the study.
Eli Lilly’s trial focuses on patients with low to moderate tau levels, who appear to benefit more from treatment than those with high tau levels.
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Eli Lilly believes patients should be tested for amyloid plague to qualify for the drug, but not for tau. The company said it tested tau in the trial to recruit patients whose condition was expected to worsen, making the study more likely to “definitely” determine the drug’s effect.
Most consultants agree that a tau test should not be required to get donanelimab, as it could limit who can benefit from the drug.
Dr. Kathleen Poston, professor of neurology, neuroscience and neurosurgery at Stanford University and an interim committee member, on Monday.
Patients taking Lilly’s drug in the trial were eligible to switch to the placebo if their amyloid levels in their brains fell below a certain threshold. At the end of the trial, 60% of donanemab participants were able to discontinue treatment.
Allowing patients to stop taking the medication when enough amyloid has been cleared could be a “motivating factor” for patients to comply with infusions and regular testing, Dolan said.
Risk of brain swelling and bleeding
About 24% of trial participants who took donanemab developed brain swelling and 31% developed brain bleeding.
Most ARIA cases were mild to moderate, with 6% of participants with brain swelling and 1% of participants with brain hemorrhage experiencing symptoms. These symptoms include headache, confusion, dizziness, nausea, and in rare cases, seizures.
In severe cases, 1.5% of patients develop brain swelling, and less than 1% develop cerebral hemorrhage.
FDA staff said that if donanemab is approved, they expect the drug’s label to include a strong “black box” warning about the risk of brain swelling and bleeding, particularly for people with two copies of the ApoE4 gene. They also expect to recommend the use of MRI to monitor patients for these side effects, among other strategies.
This is consistent with Leqembi’s approved labeling.
During the 18-month trial, 19 participants taking donanezumab died, including three with Eli Lilly’s drug, according to one agency. final data analysis By FDA staff. This compared with 16 deaths among patients taking placebo, reflecting a smaller imbalance in the number of deaths between patients who took donanelumab and those who did not.
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