Donanemab clears another hurdle
Yesterday an independent panel of experts unanimously recommended FDA approval of the anti-amyloid monoclonal antibody donanemab. I think it is very likely that full FDA approval will be forthcoming. Donanemab appears to be at least as effective as the previously approved lecanemab in removing beta-amyloid from the brain and modestly slowing the rate of cognitive decline in patients with mild cognitive impairment and early Alzheimer’s dementia. In some patients, biomarkers of beta-amyloid such as amyloid PET scans decreased below the threshold of detection, allowing the treatment to be stopped. It is not yet known if the amyloid plaques will eventually return and require additional treatment. It should be emphasized that despite completely removing detectable amyloid plaques, donanemab slows but does not stop progression of cognitive impairment. I doubt that removing beta-amyloid alone will ever result in a cure for Alzheimer’s once cognitive impairment has set in. One clue suggesting a way forward is the finding that those subjects with the least accumulation of the protein tau on PET scans had the most robust response to donanemab. These drugs seem to work best in the earliest stages of Alzheimer’s disease. Currently trials are underway to examine the effects of donanemab as well as lecanemab in preventing dementia in pre-symptomatic subjects who already have amyloid plaques in their brains. Results are still several years off.
What about safety? Both donanemab and lecanemab can cause potentially deadly side effects called ARIA (amyloid-related imaging abnormalities). Usually these are mild and often without symptoms, but rarely they can cause life-threatening swelling and/or bleeding in the brain. Three subjects in the donanemab trial died of these severe responses to the medication. The severe ARIA are much more likely to occur in subjects with two copies of the APOE-4 allele. In my opinion as a retired neurologist with two copies of APOE-4 who spent two days in an ICU with severe ARIA during the aducanumab trial, anti-amyloid monoclonal antibodies should be used only with extreme caution and frequent MRI monitoring in those with two copies of APOE-4 or in those with MRI evidence of cerebral amyloid angiopathy.
Thank you. This sets it out very clearly for us, the general public.
Thanks Dan. Any opinion on switching from Leqembi to Donanemab once it’s available? Seems slightly more effective and will require less frequent trips to the infusion center.
Best,
Lisa
That’s a great question. I honestly don’t know the answer.
Thanks, Dan. It’s great to see photos of your and Lois’ trip. Glad to know you were well enough to do it. If you are comfortable with this request, I’d like to know if your early-onset Alzheimer’s symptoms are getting worse. Or maybe the progression is so slow you don’t notice it Skip an answer if that topic is too personal to discuss here. I also wondered if people who don’t have medical insurance or who are low on funds have access to the new medications. I imagine they are quite pricey.
Love, Janice
Thanks for asking. I am still doing well. I don’t mourn the things I can no longer do, like balancing the checkbook, and I celebrate the tings I can still enjoy like reading a great book and playing with my grandchildren. You’re right that the cost of these drugs will be very high. “Medicare and Medicaid patients will make up 92% of the market for lecanemab, according to Eisai Co., which sells the drug under the brand name Leqembi. In addition to the company’s $26,500 annual price tag for the drug, treatment could cost U.S. taxpayers $82,500 per patient per year, on average, for genetic tests and frequent brain scans, safety monitoring, and other care.” quoted from KFF Health News – https://kffhealthnews.org/news/article/the-real-costs-of-the-new-alzheimers-drug-most-of-which-will-fall-to-taxpayers/
Thanks so much for everything you do ! Appreciated your comments and caution about new drugs approved by FDA . Looking forward to the day when we can see head to head trials with outcomes of the recently recommended lifestyle changes to slow AD progression ( diet, exercise, sleep, etc.) vs the new medications with risk, benefit, cost comparisons included .
Thanks for this good news. Do I simply ask my neurologist for prescription?
Check with your neurologist to see if you might be eligible for lecanumab or donanemab.
What’s the difference between Lecanemab & Donanemab
Lecanemab and donanemab are very similar anti-amyloid monoclonal antibodies. They both are very effective at removing amyloid from the brains of people with Alzheimer’s. Although the effect on removing amyloid from the brain is almost total, slowing of cognitive impairment is reduced but not halted. Both drugs have similar side effects. Rarely they can be severe including death. Lecanemab is already FDA approved. Approval of donanemab is expected soon. People with two copies of the APOE-4 gene are at higher risk of serious side effects.