Four reasons to question “new generation” monoclonal antibody Alzheimer’s drugs such as aducanumab (Aduhelm), lecanemab (Leqembi), donanemab

New Alzheimer’s Drugs Don’t Deserve the Hype (Being Patient):

A promi­nent child­hood mem­o­ry is of my grand­par­ents liv­ing with and then dying from demen­tia. As is uni­ver­sal with demen­tia, there was a dou­ble blow: watch­ing my grand­par­ents lose their iden­ti­ty and see­ing the suf­fer­ing of those clos­est to them.

… Enter three drugs, ten­ta­tive­ly FDA-approved adu­canum­ab (Aduhelm); ful­ly FDA-approved lecanemab (Leqem­bi); and donanemab … cur­rent­ly in clin­i­cal tri­als and soon to be con­sid­ered for FDA approval) that remove amy­loid, the pro­tein thought to cause Alzheimer’s dis­ease… But how use­ful are these drugs going to be?

1. Tiny ben­e­fits: In the donanemab tri­al, the peo­ple tak­ing the drug declined on aver­age by ten points on a 144-point cog­ni­tive scale … The place­bo group declined by 13 points.
2. Side effects: Through reg­u­lar mag­net­ic res­o­nance imag­ing (MRI) scans, one in six peo­ple tak­ing lecanemab was found to have evi­dence of brain bleed­ing, and one in eight had brain swelling … there have also been a few deaths attrib­uted to these drugs.
3. High prices: Adu­canum­ab was mar­ket­ed in the U.S. for $45,000 USD (£35,000) per patient per year (lat­er reduced to $20,000 USD to increase demand), and Leqem­bi for $26,500 USD … There are oth­er impo­si­tions for patients: attend­ing cen­ters every two to four weeks for drug infu­sions and reg­u­lar mon­i­tor­ing and wor­ry­ing about side-effects.
4. High­ly selec­tive tri­als: It is accept­ed that not all tri­al “effi­ca­cy” … will con­vert into clin­i­cal “effec­tive­ness” (the effect seen when drugs are giv­en to rel­a­tive­ly more com­plex patients in busy, real-world clin­i­cal set­tings). This is con­cern­ing, because there’s lit­tle wrig­gle room before the effects become unde­tectable. And, while this is the case for all dis­eases, Alzheimer’s is like­ly to be an extreme exam­ple … If the drug eli­gi­bil­i­ty is restrict­ed to match the tri­al eli­gi­bil­i­ty, then very few peo­ple will be eli­gi­ble. If eli­gi­bil­i­ty is broad­er, then already small effects are like­ly to be even small­er and side-effects more pronounced.

… the short­com­ings are so pro­found, despite decades of expen­sive tri­als and patient sac­ri­fice, I think it’s time to take the amy­loid blink­ers off and pri­ori­tise explor­ing oth­er, neglect­ed, options for treat­ing dementia.

News in Context: