I debated whether or not to even write this blog offering my opinion about donanemab. Last week there was yet another big pharma announcement of clinical trial data for a new medication as an effective treatment for those in early stages of Alzheimer’s disease (AD) … donanemab. No one wants more than I do to learn about new effective treatments for those in any stage of AD. However, I have been disappointed too many times by big pharma companies releasing announcements of positive clinical trial results without simultaneous disclosure of all supporting data and peer review commentary. Early announcements of rosy results have too often overplayed the positive effects of new medications and too often downplayed serious negative side effects. I fear that donanemab is just the latest AD medication that a big pharma company has touted as having promising results that are “statistically” significant but not really “clinically” significant, and with extremely dangerous side effects. (Please see PB # 28, posted on 10/4/22, about my serious doubts about the “significant” published results and dangerous negative side effects of lecanemab (now sold under the brand name, Leqembi), last year’s new AD medication from Eisai and Biogen. In that blog I also discuss how statistically significant differences in AD testing for new meds may be totally insignificant and meaningless with respect to functioning in the real world.)
According
to an article published in Nature on May 4, “For the second time, an
experimental drug has been shown to reduce the cognitive decline associated
with Alzheimer’s disease. On May 3,
pharmaceutical company Eli Lilly announced in a press release that its
monoclonal antibody donanemab slowed mental decline by 35% for some
participants in a 1,736-person trial — a rate comparable to that for competitor
drug lecanemab.” Lilly said it intends to seek FDA approval within
the next month or two, will issue further results at a major AD conference in
July, and seek publication of its data in a forthcoming peer reviewed journal.
Early reactions to this announcement have been mixed. According to that same Nature article,
“Researchers warn that until the full results are published, questions remain
as to the drug’s clinical usefulness, as well as whether the modest benefit
outweighs the risk of harmful side effects.
Some researchers who have reviewed the limited data released to date are
doubtful of its effectiveness.” Quoting Dr.
Marsel Mesulam, a neurologist at Northwestern
University, “The results that are described are extremely significant and
impressive, but clinically their significance is doubtful.”
As reported in the May 3 NY
Times article about donanemab, “24 percent of patients had the side effect
of brain swelling and bleeding, and 6 percent had symptoms like dizziness,
headache or fainting. Three patients in the Lilly trial died. The company reported that two to three out of 10 patients taking
donanemab progressed (to worsening stages of AD) over the next 18 months, compared
to the expected three to four patients taking a placebo.” Lilly
said that people with mild Alzheimer’s who received donanemab “showed 35% less
clinical decline over 18 months than did those who received a placebo, and 40%
less decline in their ability to perform daily tasks.”
According to the NY
Times piece, Dr. Ronald Petersen, Mayo Clinic’s director of the Alzheimer’s
Disease Research Center, said that “the donanemab results were modest but meaningful
adding that “patients
and their families must be counseled about a dire side effect of donanemab - a
risk of brain swelling that can result in death.” Dr.
Samuel Gandy, professor of Alzheimer’s disease research at Mount Sinai, noted
that whereas the results for both lecanemab and donanemab were
reported to be statistically meaningful, they have “only modest clinical
benefit.”
In
an article about donanemab published in Science on May 3, the author
wrote: “We cannot be sure that this drug will actually make a
difference in the real-world care of patients with Alzheimer’s - not yet,
anyway. This point is completely avoided in the Lilly press release, but it is
nonetheless real and we will be hearing more about it from clinicians - well,
if you listen closely above all the noise, that is.” Also noted is how the negative side effects in
the donanemab trial were worse than those in the lecanemab trial. For lecanemab, “the reported rates of ARIA-E
and ARIA-H (measures of brain bleeds) were 13% and 17% of the trial
participants, and the rates in this new donanemab trial were noticeably higher:
24% and 31%.” That same article quoted a tweet from Dr. Robert
Howard, a psychiatrist at University College London who has tested treatments
for dementia. Howard tweeted, “Looks as dangerous as lecanemab.”
I remain very skeptical
while awaiting full data and peer review of results from Lilly’s new proposed
medication, donanemab … and for the same reasons as noted in my PB #28 about
lecanemab. Here’s why: When my wife was
diagnosed with early onset AD, we knew that most people, on average, progress
through the stages of AD in about 8 years … some more quickly, some more slowly. We thought that we could be reasonably
confident of having at least 3 and maybe even 4 more really good years together
before she would progress to moderate stages of AD. And we did.
During those first few years after diagnosis, we traveled extensively both
in this country and internationally. We
played our favorite word games like Scrabble and Boggle, continued to go
bowling in our leagues, enjoyed going out by ourselves and with friends to see
plays and movies, and enjoyed just sitting on a bench at the water’s edge on nice
days. We had a very rewarding life together for those first three to four years
after diagnosis.
Had a medication such as
lecanemab or donanemab been available, would we have risked what turned out to
be nearly four really good years together to take medication hoping my wife
would be in the 35% of those who might gain an extra few good months, but all
the while risking that she could be in the group of 24% who would suffer brain
swelling or brain bleeds, stroke or death? I think not. There is just too much downside risk,
in my opinion … the high risk of negative side effects of this new medication simply
outweigh any hope that there may be a slight reduction in the rate of decline
for a few more months. I await the
published results and peer review of this new proposed medication later this summer
or fall, but I am not very optimistic.
