The media has been hyping donanemab as a major advance against Alzheimer’s disease. For example, Time’s headline read: “Eli Lilly’s Alzheimer’s Drug Shows Greatest Benefit Yet.” That is a true statement…but how helpful is donanemab for Alzheimer’s disease when it comes to things people really care about? That’s what this reader and many others want to know.
What Does the Drug Actually Do?
This person wants to know how well donanemab works.
Q. Can you comment on the new findings about donanemab? I read that in a Phase 3 clinical trial, “Donanemab slowed clinical decline by 35% compared to placebo on the primary outcome measure and resulted in 40% less decline in the ability to perform activities of daily living.” What exactly does that mean?
A. Eli Lilly created headlines with its new study of the drug donanemab for Alzheimer’s disease (AD). We hope the company will soon release more details so we can better evaluate the benefits of the medication.
All of the participants in the trial performed worse on cognitive tests as the study progressed. However, those on donanemab declined somewhat more slowly. Whether this will keep such patients out of nursing homes remains to be determined. That’s just one aspect of AD that people really care about!
What Do Patients and Families Want from AD Drugs?
Let’s be clear, dementia is devastating. It not only robs patients of their memories, it takes away their ability to function. AD makes it impossible for people to continue working. When this mind-slayer hits people in mid life, it has ruinous effects on finances.
Older retired people are also in trouble. Nursing homes can be unbelievably expensive, if they will even take someone with dementia. The annual cost can exceed $100,000 per year. If a person with AD has not been admitted to a long-term care facility, they can be refused entrance if they depend upon Medicaid.
Then there are the practicalities. People with advanced AD may not be able to care for themselves. Getting dressed may seem like an insurmountable challenge. Brushing teeth, getting to a doctor’s appointment or just interacting with friends and family can be overwhelming.
Will Donanemab for Alzheimer’s Disease Reverse the Brain Decline?
Donanemab may show the “Greatest Benefit Yet,” but that is a very low bar. None of our previous drugs have been able to meaningfully slow or stop the inevitable decline of AD.
When Eli Lilly states that donanemab for Alzheimer’s disease “showed 35% slowing of decline,” that does not mean the drug will keep patients out of nursing homes. It does not mean it will enable people with AD to recognize their grandchildren. We have seen no evidence that it will allow people to keep working or driving once the disease has progressed.
Will Donanemab Prevent the Inevitable Downward Spiral of AD?
Read the words from Eli Lilly carefully. The drug produced “less decline” than people taking placebos. We found an earlier study of donanemab published in the New England Journal of Medicine (May 6, 2021).
Here is what the authors reported:
“In this trial of donanemab, an amyloid plaque–specific intervention, in participants with early symptomatic Alzheimer’s disease, the primary analysis showed a smaller reduction in the iADRS score, by 3.20 points, in the donanemab group than in the placebo group. The iADRS ranges from 0 to 144. The minimal clinically important difference on this scale has not been established, but because we aimed to find a medicine that could slow Alzheimer’s disease progression by at least half, the trial was powered to show a 6-point difference (decreases from baseline of approximately 12 and 6 points for placebo and donanemab, respectively); this goal was not reached.”
What Does That Mean?
We know it can be a challenge to make sense out of medical jargon and scientific results. Let me try to explain what you read above. The iADRS score described above is the Integrated Alzheimer’s Disease Rating Scale. As described, it goes from 0 to 144.
It is my understanding that 144 is a perfect score. If you were able to achieve that number during testing it would mean that you have no mental decline. As your score drops, the worse your mental state is determined to be.
The people who participated in the study were all diagnosed with “early symptomatic Alzheimer’s disease.” Here are the results. Please pay attention to the iADRS score at the start of the study and at the end of the 76-week trial of donanemab for Alzheimer’s.
The researchers describe it like this:
“A total of 257 patients were enrolled; 131 were assigned to receive donanemab and 126 to receive placebo. The baseline iADRS score was 106 in both groups. The change from baseline in the iADRS score at 76 weeks was −6.86 with donanemab and −10.06 with placebo (difference, 3.20; 95% confidence interval, 0.12 to 6.27; P=0.04). The results for most secondary outcomes showed no substantial difference.”
Did you follow that? The average score at the beginning of the study was 106. Remember, 144 is the best score possible. Zero would be the worst score possible. People on nothing (placebo) declined 10.6 points over 76 weeks. People on donanemab declined 6.86 points over 76 weeks. So…on a 144 point scale, the patients on donanemab experienced 3.2 points less decline. Not nothing. But was it meaningful? Did families find the benefits impressive? How many people dropped out of the trial?
See For Yourself:
The best way to assess the results of this study is to go to this link and scroll down until you get to Figure 2. Double click to make it readable. The top graph represents “Primary Outcome iADRS Score.” It will tell you a lot about donanemab for Alzheimer’s disease. It will only take you 30 seconds and is definitely worth that amount of time to see the results for yourself.
The TRAILBLASER-ALZ 2 Phase 3 study announced by Eli Lilly on May 3, 2023 was larger than the study cited above in the New England Journal of Medicine. We look forward to seeing much more data published in a peer-reviewed journal such as the New England Journal of Medicine. That way we can compare the results from the earlier trial with the new research. We will be able to see how the iADRS score changed for people on placebo and people taking donanemab. How many people dropped out of the trial? We always find that is a key metric.
There is lots we do not yet know about donanemab. Is it a breakthrough? Will it keep patients with Alzheimer’s disease out of nursing homes? What are the possible side effects and how serious are they? You can read about some adverse drug reactions at this link.
Will we be able to answer our reader’s question at the top of this article?
“Donanemab slowed clinical decline by 35% compared to placebo on the primary outcome measure and resulted in 40% less decline in the ability to perform activities of daily living.” What exactly does that mean?
We will do our best to answer that question when we see all the data in a reputable peer-reviewed journal.
What do you think? Please add your thoughts in the comment section below.