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FDA Advisors Recommend Eli Lilly’s Alzheimer’s Drug Donanemab
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 the disease’s progress in a late-stage trial, paving the way for the company to apply for US approval.
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An approval would expand now-limited treatment options to more than 6 million Americans who have Alzheimer’s, the fifth cause of death for adults over 65 years old.
In a first vote, 11 members of the committee unanimously stated that the available data on the drug show that it is effective in treating Alzheimer’s patients in the early stages of the disease that causes loss of consciousness. But several advisers noted that more data is needed on donanemab in black and Hispanic patients, among other groups.
In a second vote, advisors unanimously said that the benefits of Eli Lilly’s donanemab outweigh its risks.
“There is a huge unmet medical need here that we hope can be met,” temporary committee member Sarah Dolan said during a date 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, vice president of Eli Lilly’s neuroscience research and development group, said in a statement.
The recommendation follows the obstacles Eli Lilly faced in bringing the treatment to market.
The FDA called a last-minute advisory panel meeting in March to further analyze 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 yet another blow to 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 the green light.
The FDA appears to be reviewing donanemab more cautiously following the polarizing approval of the ill-fated Alzheimer’s drug Aduhelm from Biogen and Eisai. The agency granted accelerated approval to this treatment despite a negative recommendation from an advisory panel.
Biogen and Eisai have since abandoned the drug.
Leqembi and donanemab are milestones in the treatment of Alzheimer’s disease, after three decades of failed efforts to develop drugs that can combat the fatal disease.
Both drugs are monoclonal antibodies that target the amyloid plaque in the brain, considered a hallmark of Alzheimer’s, to slow the progression of the disease in patients in the early stages.
But none of the treatments are cures.
Medications that target and eliminate 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 study died from severe cases of these side effects, called amyloid-related imaging abnormalities, or ARIA.
A series of obstacles have slowed the rollout of Leqembi since its approval in July, including the steps needed to diagnose Alzheimer’s disease and monitor and manage the required weekly infusions of the drug. Biogen and Eisai signaled in April that they are seeing increased adoption.
In a note Sunday, Leerink Partners analyst David Risinger said he expects limited commercial adoption of donanemab versus Leqembi because Eli Lilly’s drug has “more safety risks” and will be less convenient once it is administered once a month through the veins. This is a method known as intravenous infusion.
Leqembi is currently administered through biannual infusions, but Biogen hopes 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.
Eli Lilly’s phase three trial in more than 1,700 patients found that donanemab slowed the progression of Alzheimer’s disease by 29% compared with 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 protein in the brain called tau, which is believed to be a marker of Alzheimer’s severity. People with zero or very low levels of tau were not included in the trial’s primary analysis because researchers considered their disease was less likely to progress during the study.
The Eli Lilly trial focused primarily on patients with low to medium tau levels, who appeared to benefit more from treatment than those with high tau levels.
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Eli Lilly argued that patients must be tested for amyloid plague to be eligible for the drug, but not for tau. The company said it tested tau in the trial to enroll patients whose condition was expected to worsen, which made it more likely that the study would “clearly determine” the drug’s effect.
Most advisors agreed that tau testing should not be required to access donanemab because it would likely restrict the population that can benefit from the drug.
“From a very practical perspective, I don’t think it would be a sensible thing to have 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. fair.
Patients who took the Eli Lilly drug in the study 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 who took donanemab were able to stop treatment.
Dolan said allowing patients to stop medication when enough amyloid has been eliminated can be a “motivational factor” for patients to stick to their regular infusions and tests.
About 24% of trial participants who took donanemab experienced brain swelling, while 31% experienced brain bleeding.
Most cases of ARIA were mild to moderate, as 6% of participants with brain swelling and 1% with brain bleeding experienced symptoms. They included headaches, confusion, dizziness, nausea and, in rare cases, seizures.
Severe cases occurred in 1.5% of patients with brain swelling and less than 1% with brain bleeding.
If donanemab is approved, FDA staff said they expect the drug’s label to include a strong “boxed” warning about the risks of brain swelling 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 label of approval.
There were 19 deaths of participants taking donanemab, including the three attributed to the Eli Lilly drug, during the 18-month trial, according to a report. final data analysis by FDA staff. This compares to 16 deaths in patients who received placebo, reflecting a smaller imbalance in the number of deaths between people who took donanemab and those who did not.