What should Canadians know about donanemab’s initial drug trial release?

This is a blog post from our archive. For our latest updates about this drug, please visit alzheimer.ca/donanemab.

Over the past few years, there have been hundreds of national and international news reports about new Alzheimer’s disease drugs that use monoclonal antibodies to target amyloid in the brain.

Two of these drugs are aducanumab, which was conditionally approved by the U.S. Food and Drug Administration in 2021, and lecanemab, which released full Phase 3 trial results in 2022.

Now, a third drug, donanemab, is in the headlines. This news coverage follows drug company Eli Lilly’s May 3 release of some positive Phase 3 drug trial results.

Some of the results released so far for donanemab are indeed positive.

But the full release of trial data is expected to happen later, at the Alzheimer's Association International Conference (AAIC) in the Netherlands in July 2023.

The full trial results will be submitted for publication in a peer-reviewed clinical journal, the drug company says.

All this means that a wider and more rigorous scientific-community evaluation of donenamab’s risks and benefits are not available yet -- and are not anticipated for at least a few months.

In the meantime, here are some key questions we are hearing from people in Canada about donanemab – and some answers, too.

What is donanemab? How is it intended to work?

Donanemab is a monoclonal antibody treatment.
It is a drug taken intravenously that is designed to target amyloid plaques in the brains of people with mild cognitive impairment or the early stages of Alzheimer’s disease.
This drug is intended to bind to those amyloid plaques and to allow the body to clear or remove them from the brain. The main action for the drug to remove amyloid plaques from the brain.

What were the top results released so far from the most recent donanemab trial?

The partial results so far have been promising:

nearly half (47%) of the people on donanemab (compared to 29% on placebo) had no clinical progression of dementia at the one-year mark, with no clinical progression being defined as no decline in their CDR-SB score (see below for details on this measure);
donanemab treatment slowed clinical decline by 35% compared to placebo and resulted in 40% less decline on the ability to perform activities of daily living, as measured by the ADCS-iADL (see below for details on this measure);
more than half of all participants (52%) completed their course of treatment by 12 months and 72% completed by 18 months as a result of achieving plaque clearance (meaning the amyloid plaques were cleared from their brain). People on donanemab experienced a 39% lower risk of progressing to the next stage of disease compared to placebo.

It is important to note that these are partial results only.

How many people were in the most recent donanemab trial?

There were 1,736 people participating in the most recent trial, all were 60 to 85 years of age. They all had to have early symptoms of Alzheimer’s disease and have been diagnosed with either Mild Cognitive Impairment or with mild dementia due to Alzheimer’s disease. As part of the trial criteria, people in the trial had to have brain structure changes typical of Alzheimer’s disease.

How was the drug tested in the most recent trial?

About half of the people enrolled in the trial received the donanemab, while the other half received a placebo. Throughout the trial, scientists measured whether there were changes on a variety of tests, including:

the Integrated Alzheimer’s Disease Rating Scale (iADRS) – this scale is meant to measure cognition and activities of daily living such as managing finances, driving, engaging in hobbies, and conversing about current events;
the Clinical Dementia Rating-Sum of Boxes (CDR-SB) – a commonly used diagnostic tool that assesses memory, orientation, judgment, community affairs, home hobbies, and personal care;
the Alzheimer’s Disease Cooperative Study – Instrumental Activities of Daily Living inventory (ADCS-iADL) – this inventory assesses the competence of patients with Alzheimer’s disease in basic and instrumental activities of daily living.

What were the side effects reported so far?

As with other drugs of this type, Amyloid-related imaging abnormalities (ARIA) were found within the study. There were two types of these abnormalities reported:

Temporary swelling in an area or areas of the brain (ARIA-E).
Microhemorrhages or superficial siderosis (ARIA-H).

Temporary swelling in an area or areas of the brain (ARIA-E) occurred in 24% of people taking donanemab. Microhemorrhages or superficial siderosis (ARIA-H) occurred in 31.4% in the people taking donanemab group and in 13.6% of the people taking a placebo.

Of the people in this study, 1.6% experienced serious amyloid-related imaging abnormalities (ARIA). Two people in the trial died due to ARIA and a third person died after an incident of serious ARIA.

When will we know more about donanemab’s trial results?

The full release of trial data is expected in July 2023 at the Alzheimer's Association International Conference (AAIC) in the Netherlands

The drug company is also saying that results from the trial will appear in a peer-reviewed journal.

This timing means that wider, rigorous scientific-community evaluation of donanemab’s risks and benefits likely won’t be possible until the summer months at earliest.

How can I, or someone I know, participate in dementia drug trials and research studies in Canada?

If you or someone you know is interested in participating in a clinical drug trial or clinical treatment trial, there are a few different options available.

You can find information about clinical trials internationally at clinicaltrials.gov. It is important to note that while some of these trials have Canadian sites, many have geographic restrictions.

You can also find many Canadian dementia studies, and some clinical trials, to participate in at alzheimer.ca/find-studies.

You can also ask your doctor, neurologist or other dementia specialist about trials or studies they might know of or be involved in.

What else should I know about the field of dementia drug development right now?

There are now more than 200 dementia drugs in development internationally. A major push in the drug development field is to find drugs that treat underlying causes of dementia, not just dementia symptoms.

If you are interested in the wider field of drug development and therapy for dementia, you may want to view our recent expert panel on this topic: New dementia drugs and therapies: What Canadians should know.

Recorded on April 23, 2023, this talk covered various categories of drugs and therapies, how clinical trials work, and more, and it is available for viewing 24/7 on YouTube or on our website.

What drugs are currently approved in Canada to treat the most common form of dementia?

Currently, there are four drugs are approved in Canada to help manage the symptoms of Alzheimer’s disease, and these drugs have been used here for many years for that purpose.

You can read about them on our webpage Medications approved to treat Alzheimer's disease in Canada.

We also have a webpage where you can learn more about the general drug approval process in Canada.

What will the Alzheimer Society of Canada do about this next?

The Alzheimer Society of Canada will continue to monitor major drug news around dementia as it develops.

If you have any questions about dementia drugs and access to them, contact your regional Alzheimer Society team using the information at alzheimer.ca/find, or reach our national information line at [email protected] or 1-855-705-4636 (INFO).