It’s a prototypical design that looks at co-primary outcome measures of measuring cognition and function. The FDA still requires to see a statistical improvement on both cognition and function. Albeit, that previous bar has been lowered with the approval of Aduhelm, which doesn’t have compelling efficacy on cognition and function.
So the design, it’s 256 subjects with mild to moderate Alzheimer’s disease, MMSE of 14 to 26, and we are dosing… This is a nice oral once a day pill...
It’s a prototypical design that looks at co-primary outcome measures of measuring cognition and function. The FDA still requires to see a statistical improvement on both cognition and function. Albeit, that previous bar has been lowered with the approval of Aduhelm, which doesn’t have compelling efficacy on cognition and function.
So the design, it’s 256 subjects with mild to moderate Alzheimer’s disease, MMSE of 14 to 26, and we are dosing… This is a nice oral once a day pill. We have four arms in the study, a low, medium, and high dose of drug and placebo. And the data that we have presented recently is at a snapshot in time where 75% of the trial is complete, but we’re still blinded to the data. All we see is one single average of all four groups. That’s all we have. We don’t know who’s on what. And that will be unblinded with top line results, probably forecasting early April.
So, the primary outcome measures in the study are measuring cognition as assessed by ADAS-Cog 11, measuring function as assessed by ADCS-CGIC, and then we have two secondary outcome measures. One is measuring executive functioning via the digit symbol coding test. And we also have a secondary outcome measure of looking at plasma, Aβ42/40 ratio, as a measure of amyloid burden. And then we have so many exploratory outcome measures, including looking at a lot of other potential biomarkers of the disease of metabolism, inflammation, and whole metabolome profiling of patients before and after receiving study medication.
What we have seen is encouraging results. So, we have evidence of a possible treatment effect with improvement of cognition as assessed by ADAS-Cog 11. Even with placebo data included with the three drug treatment groups average, we see an evidence of a possible treatment effect with a reduced decline of function, perhaps improvement, as assessed by the CGIC. Again, even with placebo data included in that average. And third, three out of three, we see evidence of a possible treatment effect with improvement of executive function as assessed by DSCT. Again, placebo data in with that average.
And so the other aspect is extremely high safety. We have no SAEs, no serious adverse events, related or possibility related to study medication. No deaths, again, related or possibly related to study medication, and no deaths related or possibly related. And adverse events that are really quite a low incidence and those that we do have that could possibly be related are minor in nature. So, right now it’s looking as if this drug will be very safe in patients. That opens up the door for adding this to other medications to potentially provide the opportunity to see if there’s complementarity for even greater benefit. Although right now, the data can stand on its own as a potentially effective monotherapy for treating AD.
Now I think one of the take home messages from this is that there’s a ray of hope that this disease can be treated even when symptoms appear. And this whole mantra that the field has adopted in recent years that says that once you get mild AD, there’s no therapy that will be efficacious, that you have to treat presymptomatic Alzheimer’s patients. So we don’t adhere to that at all. And in my view, it’s a personal view that because this view of having to treat earlier was put forth to the community by large pharma as a rationalization of failure.
