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

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.

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