Not another mab ... and maybe it works

Monoclonal antibodies, with their brain swelling and microhemorrhaging, may not remain the only game in town for treating Alzheimer's disease.  (Think Aduhelm, Leqembi, and Kisunla.)  In a June press release, Annovis Bio announced completion of an apparently successful phase 2/3 trial of a new medication, buntanetap.  Rather than use antibodies to eat up amyloid plaques, this medication modulates production of the polypeptides that make up the plaques.  In addition to a reduction in the appearance of plaques, researchers noted a reduction in tau tangles.  (We discuss the relationship between amyloid plaques and tau tangles in Beating the Dementia Monster.)

Part of the good news here is that the medication was delivered orally over a relatively short period of time.  Not being a monoclonal antibody, there was no brain swelling or microhemorrhaging -- ARIA.

The trial included 353 patients, ages 55 to 85.  They were randomly assigned to receive buntanetap at one of three doses, or a placebo, on top of their standard of care for 12 weeks (roughly three months).  Compared with a placebo, cognitive function was significantly improved in patients treated with 15 mg buntanetap and in those treated with the higher dose.  

In patients treated with 30 mg buntanetap, response to treatment correlated with higher cognitive test scores at the beginning of the trial.  In other words, the higher the initial test scores, indicating less cognitive impairment, the greater the improvement in cognitive function.

When 23&Me tests you for susceptibility to Alzheimer's disease, they look for the presence of the ApoE4 gene in your genome.  (We discuss this in Beating the Dementia Monster.)  This gene makes it more likely that you will develop Alzheimer's, but (like me) you don't need the gene to get it.  And having the gene doesn't guarantee that you will develop the disease.  But having the gene does influence how well the monoclonal antibodies will work for you, and having the gene also increases your risk for brain swelling and microhemorrhaging.  But not so with buntanetap.  ApoE4 status doesn't appear to influence the side effects or how well the medication works.

Buntanetap also shows promise for treatment of Parkinson's disease, at least if started in the early stages.

So there was a reduction in amyloid plaques and tau tangles (not sure how they measured that...), and patients' cognitive test scores improved enough to get the researchers excited.  But how much did they improve?  Caregivers apparently didn't notice anyone getting better.  That's kind of important.

Annovis Bio is now preparing for a phase 3 clinical trial.  A successful trial will pave the way for FDA approval.  In the first two trials, the researchers learned a lot about effective dosing and about how to administer the drug.  Perhaps a refined treatment protocol will produce results that even caregivers will recognize.