A few weeks ago, the Food and Drug Administration (FDA) approved a new medication to treat people diagnosed with mild cognitive impairment (MCI) or in early stages of Alzheimer’s disease (AD). The medication, donanemab, clears amyloid protein plaques from the brain and will be sold by Eli Lilly under the brand name, Kisunla. 1
Readers of my Personal Blog (PB) columns may recall my
previous PB about donanemab. In PB#31,
posted on this site on 5/8/23, I noted that whereas the FDA wanted more data
before approving of this new medication, I would not have wanted my late wife
to have taken donanemab had it been available to her in early stages of AD.
My primary reasons noted in PB#31 were that the data
indicated just a modest, if even noticeable, slowing of AD symptoms for a few
months at best for some patients taking this medication … but there was also a
serious risk of negative side effects. I
wrote that, in my opinion, the risk of those negative side effects … about 25%
of patients taking donanemab suffered brain bleeds … far outweighed any possible
benefits. After receiving more clinical
trial results the FDA has now given donanemab its approval, but my opinions of
this new medication have not changed.
On July 2, 2024, Pam Belluck, health and science reporter
for The New York Times, wrote in her article, “New Drug Approved for
Early Alzheimer’s,” that this new amyloid protein clearing drug (costing
$32,000 for one year of therapy) is “the latest in a novel class of treatments
that has been greeted with hope, disappointment, and skepticism.” 1
Belluck’s article quotes Dr. Michael Greicius, a Stanford
University School of Medicine neurologist, who said he would not prescribe this
new drug for his patients. Dr. Greicius
stated that if this medication was effective, “the data should show that
individual patients who had more amyloid removed from their brains experienced
slower rates of cognitive decline.” 1 However,
Greicius said that whereas the Lilly data demonstrated successful removal of
amyloid plaque from the brain, “there is no correlation in any of their studies
between the removal of amyloid plaques and the clinical responses of individual
patients.” 1
Lilly data used an 18-point cognitive scale to compare
results of the group receiving donanemab and a placebo. Their data showed that patients receiving
donanemab had a seven-tenths of a point difference compared to those receiving
a placebo. 1 As I have written in several PBs and published
articles, there is a vast difference between statistically significant differences
demonstrated by testing in clinical trials and real-world performance. In my opinion, the possible “reward” of minor
slowing of decline for a period of several months, when weighed against a 25% risk
of brain swelling or bleeding, is just not a good enough “risk/reward” ratio.
According to the FDA, a “black box warning” will appear on
this new medication that is to be taken intravenously over about 30 minutes once
a month, and readers of this blog should take note:
“The
prescribing information includes a boxed warning for amyloid-related imaging
abnormalities (ARIA). ARIA most commonly presents as temporary swelling in
areas of the brain that usually resolves over time and may be accompanied by
small spots of bleeding in or on the surface of the brain. ARIA usually does not have symptoms, although
serious and life-threatening events rarely can occur.
Patients
who are ApoE ε4 homozygotes have a higher incidence of ARIA, including
symptomatic and serious ARIA, compared to heterozygotes and noncarriers.
Testing for ApoE ε4 status should be performed prior to beginning treatment to
inform the risk of developing ARIA.
There
is risk of infusion-related reactions, with symptoms such as flu-like symptoms,
nausea, vomiting and changes in blood pressure, and hypersensitivity reactions,
including anaphylaxis (severe, life-threatening allergic reaction) and
angioedema (swelling).
The
most common side effects of Kisunla were ARIA and headache.” 2
1 New drug
Approved for Early Alzheimer’s. The
New York Times, July 2, 2024. Access
at: https://www.nytimes.com/2024/07/02/health/alzheimers-treatment-kisunla-donanemab.html
2. FDA approves treatment for
adults with alzheimer’s disease … FDA, U.S. Food & Drug
Administration. Access at: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-adults-alzheimers-disease
