"Your Brain Health Matters."

Each month, we're exploring research to help us better understand brain diseases and the work underway here in the state to address them.

This week, the results are in on a five-year study to find out if drugs like Ozempic can slow the progression of Alzheimer's disease.

Dr.

Jeffrey Cummings is a professor with UNLV's Department of Brain Health and was the co-chair of the trial's Steering Committee.

He told us, although the results were not what he hoped for, there's still a lot to learn from the study.

♪♪ (Jeffrey Cummings) This was two very large trials that tested the diabetes drug Ozempic for the ability to treat Alzheimer's disease.

And this was all brought forward by the observation that patients with diabetes who were treated with Ozempic were less likely to get Alzheimer's disease.

So it was a very logical next step to treat Alzheimer patients with Ozempic.

And two very well-done trials were executed, and we showed no benefit for patients with Alzheimer's disease.

That was a great disappointment.

There were almost 4,000 patients in the two trials combined, and they were on the trial for two years.

So this was a very big investment by the patients and their families in terms of testing this drug.

But we learned an enormous amount.

That's the important thing.

We learned an enormous amount even though the trial was negative.

-What did you learn?

-Well, we had the hypothesis that inflammation present in the body is driving part of Alzheimer's disease progression.

And we knew that this drug, Ozempic, reduced inflammation in patients with diabetes, and we thought that's why they're getting less Alzheimer's disease when they're treated with Ozempic.

And so we tested that hypothesis.

And we showed absolutely that we can decrease inflammation in the blood when patients are treated with Ozempic, but it didn't translate into benefit for the patients.

Now, the important learning there is that the peripheral blood is a bad target for developing treatment for Alzheimer's disease.

It can't guide us in the way that we had hoped to find new treatments for Alzheimer's disease.

Well, that's very important because it extends across the whole field of drug development for patients with Alzheimer's disease.

That's a tremendously important lesson.

-So then what do you do with that in terms of testing?

Do you no longer test a specific way?

-There are about 20 drugs in development for inflammation in Alzheimer's disease.

So we'll now re-examine all of those programs, all of the biomarkers, the blood tests that they are using to guide those programs to see whether the learnings from the Ozempic trial can help make those trials better.

-That sounds like so much more work that everyone now has to do.

-It's a lot more work, but it's going to get us to better drugs for patients.

And ultimately, that's the goal of the work we do is, can we treat patients better?

Can we slow their disease?

Can we prevent their disease?

Can we delay their disease?

These are the goals that we're striving to achieve, and every lesson contributes to that, to that project.

-There has been some reporting that perhaps patients who received the semaglutide didn't get enough, that maybe it should have been injected versus taken orally, and that maybe there still could be some promise here.

-That's a very good question.

And we think that that's not the case, because there was substantial weight loss.

Not surprisingly, this is a drug which is also used for weight loss.

And we saw weight loss in the Alzheimer patients, and we saw that they tolerated it well, but we wouldn't want a higher dose that would produce greater weight loss, because these are already older, frail patients.

And the weight loss was proportional to their baseline weight.

So if they were more overweight at baseline, then they lost more weight; and if they were thin at baseline, they lost very little weight.

Nevertheless, we wouldn't want them to lose more weight, because we think that could lead them to some sort of healthcare compromise.

-How did you take this news personally?

-I mourned these data when I saw them.

I was so disappointed.

We have been working on this trial for five years.

We involved 4,000 patients in 40 countries, 255 trial sites.

This was an enormous undertaking, and I was so disappointed.

I really thought that the information we had from the diabetics, the information we had from a laboratory experiment, which supported the efficacy of semaglutide for the treatment of Alzheimer's disease, was going to come together to predict a positive trial.

And it didn't, and I was very disappointed.

And you have a grieving process to go through when you have invested five years of your lives in doing something and it turns out to be negative.

-You seem to be in a different state right now?

Is that accurate, or is it just for the cameras?

-I am in a different state now because I'm starting to see the lessons that we are learning from this trial, and we've just barely scratched the surface of the data.

We've only had the data for about three weeks from the end of the trial, and there are so many relationships to examine.

For example, we saw changes in the spinal fluid that looked like a small magnitude therapeutic effect.

So we will go back and look at those patients who had these very positive changes in the spinal fluid to look at whether they also had a clinical benefit, because that's the kind of hint that would tell us what we have to achieve in order to advance this kind of drug to a therapy for patients.

-Do these results negate the idea that semaglutide is a miracle drug?

-Semaglutide has had so many beneficial effects.

It is really effective in diabetes.

It is really effective in obesity.

We can see it reduces cardiovascular events like heart attacks and stroke.

We can see that it has a beneficial effect in liver disease.

We can see that it improves kidney function.

It probably has a role in addiction.

So there are many benefits of semaglutide.

None of them are challenged by these results.

What we see is that they don't translate into the very difficult, challenging problem that Alzheimer's disease represents in the brain.

-What comes next?

-What comes next is the trial has to be stopped worldwide.

And that's actually a very complicated process in itself, because you have to make sure that you have all of the data from all of the participating sites so that no patient had even one clinic visit that didn't count in the data that we have.

We have to understand it completely and fully, so all of-- And, of course, the patients have to be told.

You know, we made great efforts to get the information to the patients as fast as possible so that they don't read it in the newspaper and realize they were in a failed trial, a negative trial.

So the trial has to-- is going to be closed now, and then we start examining all the data.

And I still think this class of drugs will be re-examined.

We knew from the beginning that semaglutide itself had a peripheral effect, and we thought that would translate into a brain effect but that the drug itself did not enter the brain.

And it is possible that a drug with a similar mechanism of action but one that enters the brain might still have a benefit specifically in Alzheimer's disease.

And that must be tested.

-Is it too soon to ask what's the next promising treatment in the pipeline?

-Right now we have two drugs that are approved for intravenous therapy for removal of the toxic protein of Alzheimer's disease, and we have one in trials now that is doing everything the current drugs are faster and safer.

So we absolutely can see the next generation of those drugs.

We have a drug that is targeting another form of toxic protein in the brain.

There are many promising candidates in the pipeline that we're really excited about.

-As for what you can do to prevent Alzheimer's disease, we'll cover that in our next segment of "Your Brain Health Matters."