Donanemab is a biological drug that slows the progression of early Alzheimer’s disease. 

There is currently no cure or disease-modifying treatment for Alzheimer’s disease. 

Donanemab has shown positive results in its first trials.

Donanemab, also known as N3pG, is an antibody produced in mice that targets an abnormal protein, amyloid beta (Aβ).

It is an immunoglobulin G1 monoclonal antibody, directed against insoluble modified N-terminal truncated form of beta amyloid present only in brain amyloid plaques.

Donanemab Binds to N- terminal truncated form of beta amyloid, and aids plaque removal through microglial mediated phagocytosis.

Donanemab targets amyloid plaque, potentially reducing the excess protein which may be a factor in Alzheimer’s disease.

Donanemab is very effective at eliminating its target, cerebral, amyloid, but the clinical effectiveness is comparatively weak.

Amyloid imaging technology have linked the excess Aβ peptide outside the cell with the development of Alzheimer’s disease.

The overproduction of the Aβ peptide creates a plaque in certain parts of the brain, disrupting neuron transmission.

Donanemab attacks the soluble and insoluble plaque buildup, slowing down the progression of the disease.

Lilly revealed that there were adverse events for the 37 people who received the treatment and 12 volunteers who received the placebo. 

The highest dose of Donanemab infused into the blood stream reduced the effect of the plaque burden in the brain.

Donanemab was found to be very immunogenic, creating an immune response that increases the efficiency of the original antibody infused. 

Patients may have an infusion reaction which included chills, flushing, dizziness, rash, and fever. 

Most people developed anti-drug antibodies lowering the drug’s effectiveness, with a short half-life of ten days.

Increase in dosage leads to a larger percentage of patients experiencing symptomatic amyloid related imaging abnormalities rising to 1 in 4 participants. 

Auto-antibodies were produced in nearly every patient.


The Phase II trial indicated  donanemab slows down the development of AD; but with the side effects still being problematic.

It was concluded that there was no substantial difference in the results between the placebo group and the patients infused with donanemab.

A Phase III study showed the drug could slow the pace of Alzheimer’s disease by 35%: 1,736 people treated with donanemab showed slowing of Alzheimer’s progression at 76 weeks, with 24% of the people displaying cerebral edema.

Among participants with early symptomatic Alzheimer, disease, and amyloid, and tau pathology, donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau, and in the combine low/medium and high tau pathology population

Overall, cognition and daily function continue to decline in all participants on the study, but treatment delayed progression on the primary outcome by about four months.

Donanemab is associated with a 76.4% amyloid plaque removal on PET at 76 weeks.

Cerebral edema, amyloid-related imaging abnormalities with edema or effusions’ (ARIA-E); some of these people being asymptomatic and others symptomatic.

Donanemab decreased whole brain volume and increased ventricular volume.

Amyloid related imaging abnormalities were seen in about 37% versus 15% in the placebo group and were seen in 40.6% of APOE e4 homozygotes.

Micro hemorrhage occurred in 26.8% of patients versus 12.5% in the placebo group.

A large percentage of symptomatic patients discontinued the drug because they experienced feelings of nausea.

APOE4 individuals have a higher risk of brain edema and amyloid  related imaging abnormalities when treated with monoclonal antibody agents.

APOE genotaping is recommended prior to Abeta targeting monoclonal antibody treatments.

The slowing of decline was more pronounced in those with low/medium tau pathology and less pronounced in APOE E4 homozygotes.

Leave a Reply

Your email address will not be published. Required fields are marked *