Status of Eli Lilly’s New Alzheimer’s Drug: Donanemab

A new drug for the early stages of Alzheimer’s disease is closer to becoming available to the public. Donanemab, made by the pharmaceutical company Eli Lilly and Co., is working its way through clinical trials and has shown benefits including slowing the progression of symptoms like memory loss.

Donanemab is an antibody that targets amyloid-beta, which forms in the brains of people with Alzheimer’s disease and related dementias. Alzheimer’s disease is our 6th leading cause of death and affects more than 6 million Americans. The number of cases is expected to more than double in coming years, making pharmaceuticals like donanemab crucial to slowing the impact of this deadly disease.

On this page, we’ll take a closer look at donanemab, including how the drug works and when it might hit the market.

Benefits & Side Effects of Donanemab

Benefits
Evidence suggests donanemab can slow the progression of Alzheimer’s disease when taken by individuals in the early stages of the disease. It can’t cure Alzheimer’s (there is no cure for most types of dementia), but memory, thinking ability, and movement might stay stronger longer after taking the drug. Some of the evidence that donanemab can help with Alzheimer’s disease include results from clinical trials:

– PET brain scans showed reduced plaques between cells in the brains of some participants
– Thinking ability declined more slowly for individuals who took donanemab, compared to placebo

For much more on clinical trials, see below. The results of testing donanemab on people were good enough that the Food and Drug Administration called it a “breakthrough,” and the process of development and review has been sped up.

Side Effects
Brains with dementia become smaller over time as cells weaken and die, but researchers said there was an association in trial subjects between donanemab and greater brain-volume loss than the subjects who took placebo. There was also a higher rate of amyloid-related imaging abnormalities (ARIA, also called “cerebral edema”), which causes swelling in the brain. The ARIA are usually asymptomatic, meaning they show up on scans but can’t be felt, though some of the donanemab trial subjects experienced difficulties concentrating.

Some experts have suggested that the clinical trials for donanemab are not long enough to fully assess the long-term consequences of the drug’s side effects. Alzheimer’s disease takes years to move through stages, and so observation over that same amount of time might be necessary to understand the impact on the brain and whether benefits shown in trials hold up.

Other side effects observed in a low percentage of subjects included brain bleeds, siderosis (buildup of iron in the brain and spinal cord), and nausea.

How Donanemab Works

Donanemab is an antibody that sticks to clumps of amyloid-beta plaques, found in the brains of people with Alzheimer’s disease, and signals the immune system to attack those clumps and clear them out. Specifically, donanemab is a monoclonal antibody, which means it was designed to mimic our natural antibodies and tell the immune system where to find and fight harmful cells.

Amyloid-beta is a normal protein that occurs in healthy brains, but in the brains of people with Alzheimer’s disease it builds up between brain cells (neurons) and harms their ability to communicate. When brain cells can’t communicate, thinking and movement become much more difficult.

Another protein that also tangles in the brains of people with Alzheimer’s disease is called tau, and scans have shown that there was a reduction in both amyloid-beta and tau in the brains of people who took donanemab for clinical studies.

Compared to Other Alzheimer’s Medications
Donanemab works in a similar fashion to another medication that recently made headlines as the first Alzheimer’s drug to receive FDA approval in more than 17 years: aducanumab. Both drugs are administered intravenously. Aducanumab and donanemab are also similar in that they are both monoclonal antibodies (see explanation above) that specifically target amyloid-beta. An important difference, obviously, is that aducanumab has achieved FDA approval and is available now, whereas donanemab is probably still years away. More on aducanumab (brand name Aduhelm).

The other medications approved specifically for Alzheimer’s disease and related dementias are cholinesterase inhibitors (brand names Aricept, Razadyne, and Exelon) and memantine (brand name Namenda). These medications are taken as a pill, and studies have shown they help strengthen communication between brain cells, which can improve symptoms like memory loss.

Cholinesterase inhibitors and memantine can be paid for through Medicare if prescribed by a doctor. Whether aducanumab (Aduhelm) will be covered by Medicare has yet to be determined, and it could be years before cost and coverage are decided for donanemab. For more on medications for Alzheimer’s, including supplements, antidepressants, and antipsychotics, click here.

Status of Clinical Trials of Donanemab

Donanemab is currently in the third stage of trials, and, unfortunately, there are no longer openings for subjects to participate. The study is expected to be completed in December 2023, and more than 1,000 participants are taking the drug, or a placebo, so that researchers can learn more about donanemab’s effectiveness.

In the first phase of clinical trials, PET brain scans showed that individuals who took super high doses of donanemab had less amyloid-beta in their brains after six months. This unfortunately doesn’t cure Alzheimer’s but it does slow down the disease’s progression. Memory, movement, and thinking ability might stay stronger longer as a result of the medicine.

During Phase 2, in fact, the drugmaker Lilly tested 272 subjects on their ability to think and do instrumental activities of daily living (IADLs) like prepare meals or use the telephone, and said donanemab slowed the decline of thinking ability in people with Alzheimer’s by 20-40%. This was compared to subjects who were given a placebo and showed predictable change. There was also some evidence that tau protein tangles, another symptom of Alzheimer’s, also declined, though less than amyloid-beta. (In normal brains, tau helps cells receive nutrients and stay healthy.)

When Will Donanemab Become Available?

The ongoing phase 3 trial to test donanemab’s effectiveness is expected to conclude in December 2023, and FDA approval would come after the data is reviewed, a process that typically takes 6-10 months. The bottom line is that donanemab probably won’t be available until 2024 or later. The goal of drugmaker Eli Lilly is to have donanemab available for people with Alzheimer’s within the next five years.

A promising development, however, came in June 2021 when the Food and Drug Administration granted the “breakthrough therapy” designation to donanemab. Breaththrough therapies are considered by the FDA to have shown notable promise, and the designation allows for a slight speeding up of the process to develop and review drugs for common and serious illnesses (in this case Alzheimer’s disease).