Donanemab's "mixed" results

On April 7, we wrote about recent research results with Eli Lilly's monoclonal antibody, donanemab.  In an article in the New England Journal of Medicine, researchers had characterized the results in terms of primary and secondary outcomes.  After 72 weeks, researchers were finding positive results on the primary outcomes, but the secondary outcomes were "mixed."  I did not have access to the actual article, only the abstract, and I wondered what was going on with the secondary outcomes.

So Dr. Freeman, who reviewed the manuscript of Beating the Dementia Monster for me, shared his paper copy of the NEJM with me, and I was able to read the article in its entirety.  (I didn't read the whole thing, just the important stuff.)  And so I found out about the mixed results in secondary outcomes.

The first thing that struck me in the secondary outcomes was that there was no improvement in hippocampus volume or volume of the ventricles when compared to the placebo.  The biomarkers used to diagnose my Alzheimer's disease were my shrinking hippocampus and my expanding ventricles.  (Expanding ventricles are a proxy for volume loss of the whole brain.)  Also there was no meaningful difference in tau protein loading with respect to placebo and non-placebo participants.  We discuss the significance of tau in Beating the Dementia Monster.  These results make me wonder to what extent donanemab is able to address the actual disease process.

The mini mental status exam (MMSE) was one of four other secondary outcomes based on cognitive testing.  You will recall that I was initially diagnosed with Alzheimer's disease based on my poor MMSE score.  The MMSE is a fairly simple test, but it is often considered sensitive enough to be used to measure changes in cognition in research.  Nevertheless, more comprehensive tests are considered more reliable.  As with the other three secondary test measures, subjects showed some improvement, but not as much as the primary outcome -- the iADRS score we discussed in the April 7 post. 

These results are relatively positive, and they seem to be mostly in keeping with Eli Lilly's expectations.  However, we should hope that further testing will find better cognitive improvement, as well as improvement in biomarkers.  

This was a phase 2 trial, which means it had a smaller number of subjects (257 patients, about 1/2 receiving the placebo).  It is likely to go to phase 3, which will have a broader base of participants.  It is not unusual to have different results in a later trial.