Eli Lilly Alzheimer's Disease Treatment Approved by FDA, What to Know

Last July, the FDA approved a similar drug, lecanemab (Leqembi), from Japanese drugmaker Eisai and Massachusetts-based drugmaker Biogen.

Both drugs are monoclonal antibodies, given as IV infusions, that target the buildup in the brain of plaques caused by the clumping together of the beta-amyloid protein.

In June, the 11 members of the FDA panel voted a unanimous “yes” to the question of whether donanemab is effective for the treatment of patients with early stages of Alzheimer’s disease. Advisors also voted unanimously that the benefits of the drug outweigh its risks.

However, some advisors said during the meeting that more data are needed on the benefits of the drug for Black and Hispanic patients, as well as other groups.

Donanemab has faced a long road to get to this point. On March 8, Eli Lilly announced that approval of the drug would be delayed.

The FDA had reversed its fast-track approval of donanemab and called a meeting of its outside advisors to review the drug’s safety and efficacy.

Eli Lilly said it had expected the FDA to approve the drug by the end of the first quarter of this year, which had already been pushed back from an expected earlier approval of sometime last year.

Dr. Howard Fillit, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said in a statement in March that the FDA’s decision is not a “setback,” but is a sign that the FDA is “doing its due diligence” to ensure the safety and efficacy of donanemab.

“The decision to hold an advisory committee before granting approval follows the regulatory process that was used for the other drugs in this class, including Leqembi,” he said.

In June the FDA advisory committee discussed the results of Eli Lilly’s phase 3 clinical trial, published in JAMA in July 2023. The trial, called Trailblazer-Alz 2, tested the efficacy and safety of donanemab in people with early symptomatic Alzheimer’s.

As with the Leqembi trial, participants in the donanemab trial took cognitive assessments and underwent brain scans to measure the level of beta-amyloid plaques.

The panel also looked at the donanemab study’s unique trial design. This includes allowing participants to stop treatment when scans showed that the beta-amyloid plaques had been cleared from the brain. In contrast, the clinical trial for Leqembi had no designated stopping point.

“A big question about this [aspect of the trial] is how it might be implemented in real-world practice. Do we stop medication in patients? Do we have to repeat PET scans?” said Dr. James Galvin, founding director of the Comprehensive Center for Brain Health and professor of both neurology and psychiatry and behavioral sciences at the University of Miami Miller School of Medicine in Florida.

Another unique aspect of Lilly’s trial is that it measured the level in the brain of a protein called tau, which collects inside neurons in people with Alzheimer’s disease.

“Clinically, we have no good way of measuring this,” Galvin told Healthline. “So again, how might this be implemented in practice?”

The clinical trial for donanemab, which included more than 1,300 participants with early symptomatic Alzheimer’s disease, separated participants based on the level of tau.

Among participants with “low or medium” levels of tau, people who received donanemab had a 35% slower decline in the ability to think clearly and perform daily activities, compared to those receiving an inactive placebo.

When researchers also included people with high levels of tau — which suggests they are further along in the course of the disease — the benefit of donanemab compared to placebo was 22%.

In addition, 47% of people who received the drug showed no decline on a test of disease severity after one year, compared to 29% among people in the placebo group.

In addition, 47% of people in the “low or medium” tau group who received the drug showed no decline on a test of disease severity after one year, compared to 29% among people in the placebo group.

The main safety concerns of donanemab are brain swelling (edema) and micro-bleeding (hemorrhages), both known as amyloid-related imaging abnormalities, or ARIA.

In the clinical trial, among people receiving donanemab, micro-bleeding occurred in 31.4% and brain swelling in 24%.

ARIA usually does not cause symptoms, the company said in a release, but it can be serious and life-threatening. In the trial, three people died from a serious case of ARIA.

The rate of ARIA was lower in the clinical trial for Leqembi, but the drug has been linked to patient deaths as well.

“The seemingly higher rate of ARIA with donanemab compared to lecanemab is of concern and requires further scrutiny [by the FDA] that, in the long run, will serve to benefit current and future generations of patients with Alzheimer’s disease,” Dr. Seyed Sajjadi, a neurologist at UCI Health in California, told Healthline.

These side effects are serious enough to raise concerns among experts about whether these drugs are worth the risks.

“[Some] clinical neurologists continue to not use this family of medications, as they have not significantly improved patient’s memory loss in the drug trials, and have caused severe cerebral edema and intracranial bleeding,” Dr. Clifford Segil, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, told Healthline.

So far, drugs that target beta-amyloid plaques in people with Alzheimer’s disease have been slow to take off.

Before the approval of Leqembi, the FDA granted accelerated approval of Biogen’s Alzheimer’s drug aducanumab (Aduhelm) in 2021, despite the FDA’s advisory committee not supporting the drug moving forward.

The subsequent drug approval was met with criticism from the scientific community. Biogen discontinued Aduhelm last month.

Leqembi had a smoother route to FDA approval, but as of February, only about 2,000 people were taking the drug, Biogen said Feb. 13 on its quarterly earnings call — far short of its goal of 10,000 by the end of this month.

This limited reach of Leqembi may be due to the number of brain scans and tests patients must undergo before starting treatment, or patient and physician concerns about the potential serious side effects.

In March, Segil said he thought the FDA committee should not recommend the drug’s approval.

“Both [Leqembi and Aduhelm] are without any data showing they cause meaningful improvements in memory loss,” Segil noted, “and there is no post-market surveillance data to indicate they cause any noticeable improvements in patients using them.”

The FDA has approved a new drug to treat Alzheimer’s disease.

The news comes weeks after an independent panel of advisors for the FDA voted to endorse Eli Lilly’s experimental Alzheimer’s drug donanemab. The committee found that the drug was effective and that the benefits outweighed the risks.

The drug targets the buildup of plaques in the brain caused by the clumping together of the beta-amyloid protein. It is the same mode of action as Leqembi, from Japanese drugmaker Eisai and Massachusetts-based drugmaker Biogen.

The main safety concerns seen with donanemab in clinical trials was swelling (edema) and micro-bleeding (hemorrhages), two types of amyloid-related imaging abnormalities, or ARIA.