The FDA's advisory committee has recommended approval of Eli Lilly's Alzheimer's drug donanemab.

• The FDA is likely to approve Eli Lilly's Alzheimer's drug donanemab after a panel of independent advisors recommended it.
• Another Alzheimer's drug, Eli Lilly's, would enter the U.S. market after Leqembi from Biogen and Eisai.
• The expansion of treatment options for the more than 6 million Americans of all ages who have Alzheimer's, the fifth-leading cause of death for adults over 65, would require an approval.

On Monday, a group of independent advisors to the Food and Drug Administration recommended approval of Eli Lilly's Alzheimer's drug donanemab, which could lead to full approval in the U.S. later this year.

Although the FDA is not obligated to follow the advice of its advisory panels, it usually does so. If approved for use, Eli Lilly's donanemab would be the second Alzheimer's drug to enter the U.S. market after Leqembi from Biogen and Eisai.

The expansion of treatment options for the more than 6 million Americans with Alzheimer's, the fifth-leading cause of death for adults over 65, would require an approval.

Although 11 committee members agreed that available data indicates that donanemab is effective in treating Alzheimer's patients at the early stages of the disease, several advisors pointed out that more data is necessary on the drug's effectiveness in Black and Hispanic patients, as well as other groups.

The unanimous consensus of advisors was that the advantages of Eli Lilly's donanemab outweigh its risks.

Sarah Dolan, a temporary committee member and consultant for Critical Path Institute, stated during a Monday meeting that there is a significant medical need that requires attention.

The recommendation follows snags Eli Lilly faced in bringing the treatment to market.

In March, the FDA held a last-minute meeting of an advisory panel to reassess the safety and effectiveness of Eli Lilly's drug in a late-stage trial, only weeks before the deadline for the agency to make a decision on the treatment.

Eli Lilly faced another setback with donanameb as the FDA rejected the drug in January 2020 due to insufficient data.

After three decades of unsuccessful attempts to develop Alzheimer's medications, leqembi and donanemab represent significant milestones in the treatment of the disease.

Both drugs are monoclonal antibodies that target amyloid plaque in the brain, which is a hallmark of Alzheimer's disease, to slow the progression of the disease in patients at the early stages of it.

But neither of the treatments are cures.

The use of drugs that target and eliminate amyloid plaque can result in severe and potentially fatal brain swelling and bleeding in patients. In a late-stage trial, three patients who took Eli Lilly's drug experienced severe cases of amyloid-related imaging abnormalities (ARIA), which led to their deaths.

Since its approval in July, several obstacles have delayed Leqembi's implementation, including the process of diagnosing Alzheimer's and administering and managing the weekly infusions. However, Biogen and Eisai reported in April that adoption rates are increasing.

David Risinger, a Leerink Partners analyst, predicts that donanemab will have limited commercial adoption compared to Leqembi due to Eli Lilly's drug's safety concerns and inconvenience, as it is administered once a month through intravenous infusion.

Biogen plans to launch an injectable version of leqembi next year, with Risinger predicting that donanemab will generate $500 million in sales by the end of the decade.

How effective is Eli Lilly's Alzheimer's drug?

A phase three trial by Eli Lilly involving over 1,700 patients showed that donanemab slowed the progression of Alzheimer's by 29% compared to a placebo after 18 months, according to a traditional tool used to assess dementia severity.

Those results are comparable to those seen with Leqembi.

The primary analysis of Eli Lilly's phase three trial for Alzheimer's disease only included patients who tested positive for amyloid plaque and had high levels of tau, a protein thought to be a marker of disease severity. Patients with low levels of tau were excluded from the analysis because researchers believed their disease was less likely to progress during the study.

The trial of Eli Lilly primarily centered on patients with low-to-medium tau levels, who seemed to experience greater benefits from the treatment compared to those with high tau.

Eli Lilly contended that patients should undergo amyloid plaque testing to qualify for the drug but not tau. The company explained that it tested for tau in the trial to enroll patients whose condition was anticipated to deteriorate, increasing the likelihood of the study accurately determining the drug's impact.

The majority of advisors concurred that mandating tau tests to obtain donanemab would limit the number of people who could benefit from the medication.

Dr. Kathleen Poston, a temporary committee member and professor in neurology, neurological sciences, and neurosurgery at Stanford University, stated during a Monday meeting that from a practical standpoint, having this as a barrier would not be wise.

In the Eli Lilly trial, patients were eligible to switch to a placebo if their amyloid levels fell below a certain threshold. By the end of the trial, 60% of donanemab participants were able to stop treatment.

Allowing patients to stop the drug once enough amyloid has been removed could motivate them to adhere to their infusions and testing, according to Dolan.

Risks of brain swelling, bleeding

Brain swelling was experienced by 24% of trial participants who took donanemab, while 31% experienced brain bleeding.

The majority of ARIA cases were mild to moderate, with 6% of participants experiencing brain swelling and 1% experiencing brain bleeding. Symptoms included headache, confusion, dizziness, nausea, and in rare cases, seizures.

Less than 1% of patients with brain bleeding experienced serious cases, while more than 1.5% of those with brain swelling did.

If donanemab is approved, the FDA expects 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. The FDA also expects recommendations for MRIs to monitor for those side effects in patients, among other strategies.

That is consistent with Leqembi's approval label.

The final analysis of data by FDA staff revealed that there were 19 deaths among donanemab participants, including three attributed to Eli Lilly's drug, during the 18-month trial. This is compared to 16 deaths among placebo patients, indicating a smaller imbalance in the number of deaths between those who took donanemab and those who did not.