[Updated] Your questions, answered: What should Canadians know about Donanemab (Kisunla™)
On July 2, 2024, the United States Food and Drug Administration granted full approval to the drug donanemab (brand name Kisunla). Health Canada accepted the drug for review in February 2024.
Note to readers: This story was updated with more information. Refer to the bottom of this webpage under the heading "Updates since this story was first posted" for more details.
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.
One of these drugs is lecanemab, which was given full approval by the U.S. Food and Drug Administration on July 6, 2023. Another is aducanumab, which was conditionally approved by the same U.S. agency on June 7, 2021.
Recently, a third drug, donanemab, has been in the headlines.
On July 2, 2024, the United States Food and Drug Administration granted full approval to the drug donanemab (brand name Kisunla).
On July 17, 2023 drug company Eli Lilly released full Phase 3 drug trial results at the Alzheimer’s Association International Conference in the Netherlands.
The Journal of the American Medical Association has also now posted the full set of Phase 3 donanemab trial results on its website — along with some important editorials about the pros and cons of this drug study.
Some of the results released so far for donanemab are indeed positive.
Yet this drug is not a cure. What it can potentially do is slow the progression of Alzheimer’s disease in some people.
This drug is only for patients with mild cognitive impairment or mild dementia stage of Alzheimer’s disease. It is not for people in the later stages of that disease. And it is not for people with other forms of dementia.
It will take time for a wider and more rigorous scientific-community evaluation of donenamab’s new, full Phase 3 trial data.
There are also at least four other Phase 3 trials of donanemab that are currently in progress. These studies won’t be complete until 2024, 2025 and 2027.
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.
- In sum, the main action for the drug to remove amyloid plaques from the brain.
What were the key results from the most recent donanemab trial data?
- The drug was able to slow down disease progression in some people.
- Nearly half (47%) of the people on donanemab (compared to 29% on placebo) had no clinical progression of dementia after one year. (No clinical progression was defined as no decline in their CDR-SB score; see below for details on this measure.)
- Treatment with donanemab reduced amyloid plaque on average by 84% after 18 months, compared with a 1% decrease for people taking a placebo.
- People on donanemab experienced a 37% lower risk of progressing to the next stage of disease compared to people taking a placebo.
Did this drug work better for some people than for others?
Yes. A few different factors came into play:
- Donanemab seemed to be more effective in people who had mild cognitive impairment than it was in people who were in the early stages of Alzheimer’s disease.
- The drug also seemed to be more effective in people under 75 than it was in people over 75.
- The drug seemed to be more effective in people with low-to-medium tau levels than in people with higher levels of tau protein.
What major concerns have emerged about this research on donanemab so far?
- Some researchers have pointed out that the group of people participating in this most recent trial wasn’t diverse enough to ensure that the drug would be safe and effective for a variety of people.
- Those researchers note that 91.5% of this Phase 3 trial group was white. By comparison, population census data for the U.S. (where the trial was based) is 75.5% white.
- As a result, those researchers conclude that, “similar to previous trials of lecanemab and aducanumab, this donanemab trial does not provide sufficient evidence of safety or efficacy among people racialized as American Indian or Alaska Native, Asian, Black, or Hispanics.”
- Furthermore, most people who are living with dementia have multiple health issues. But the group of people in the trial tended to only have dementia as their main health issue. So the group of people the drug was tested on also doesn’t match real-world populations when it comes health condition status.
What major concerns have emerged about these monoclonal antibody drugs for Alzheimer’s disease generally?
- Another concern that some researchers have raised is around accessibility barriers to drugs like donanemab, lecanemab and aducanumab.
- All three of these drugs are taken intravenously monthly or twice monthly. This requires access to specialized medical facilities and transport to and from them.
- All three of these drugs also require frequent brain scanning to monitor effectiveness and safety.
- Resources for intravenous infusion and for brain scanning are not widely available in minoritized communities, some researchers point out.
- Other researchers note that, at best, these monoclonal antibodies can only be considered for a subset of people with Alzheimer’s disease. And that also, even within this subset, people with high tau levels may not benefit.
How many people were in the most recently completed 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 Clinical Dementia Rating Scale Global score (CDR-G) - a full summary measure designed to measure the overall severity of dementia accounting for the six different areas listed above in the CDR-SB.
- 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, or have more data about, donanemab/Kisunla?
Now that the full Phase 3 trial results have been released, scientists internationally will be reviewing the data closely. This wider, rigorous scientific-community evaluation of donanemab’s risks and benefits will continue for some time.
According to clinicaltrials.gov, there are also at least four other Phase 3 trials of donanemab still going on. These studies are due to complete in 2024, 2025 and 2027. When those studies are released, we will know even more about donanemab’s risks and benefits.
Can people in Canada use donenamab/Kisunla?
A few Canadians have taken or are taking donenamab /Kisunla as part of experimental drug trials. In Canada, the drug is not available outside of those experimental drug trials. The Alzheimer Society of Canada supports any and all findings Health Canada has had or may have in future about the safety and efficacy of dementia drugs for people living in Canada.
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.
Will Health Canada review, or has it already started reviewing, donenamab/Kisunla?
Yes. According to Health Canada's webpage about new drug submissions under review, Health Canada accepted the drug for review in February 2024. This means the drug is currently in the review process with Health Canada.
How long will it take for Health Canada to review the drug and make a decision?
Health Canada reviews of drugs can take different lengths of time. The Health Canada website explains that timing can vary depending "on the product being submitted and the size and quality of the submission, and is influenced by [our] workload and human resources."
What else should I know about the field of dementia drug development right now?
There are now more than 127 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.
It’s also important to be aware that more than 50 different diseases and conditions can cause dementia. So drug development is going to be different for different types of dementia. The drugs most often covered in the news are those that aim to treat Alzheimer’s disease, the most common form of dementia.
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.
Updates since this story was first posted
October 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) (United Kingdom) approved a product licence for donanemab (Kisunla) for use in adults in the early stages of Alzheimer’s disease who have one or no copies of the apolipoprotein E4 gene (ApoE4). The National Institute for Health and Care Excellence (NICE’s) draft guidance at this time does not include approving funding for use in the National Health Service (NHS).
In Japan on September 24, 2024, donanemab was approved to manufacture and market as a treatment for mild cognitive impairment and mild dementia due to Alzheimer's disease.
What will the Alzheimer Society of Canada do about this next?
During May-July 2024, the Alzheimer Society of Canada developed an online survey to gather the experiences of people living with Alzheimer's disease or mild cognitive impairment (MCI) due to Alzheimer's disease, and their caregivers, and those who were involved in clinical trials of Leqembi (lecanemab) and/or donanemab. The results of this survey (see links below), were submitted to Health Canada to ensure that the voices of people with lived experience are represented and considered during the review process.
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 info@alzheimer.ca or 1-855-705-4636 (INFO).
Alzheimer Society groups are always here to help support people in Canada who are impacted by dementia and to support quality of life.
Last updated: October 31, 2024