Acoltremon produces rapid and sustained outcomes for patients with dry eye disease
In part 4 of a 5-part video series, Marjan Farid, MD, of the University of California, Irvine; Karolinne Rocha, MD, PhD, of the Medical University of South Carolina; Nathan Lighthizer, OD, of the Northeastern State University Oklahoma College of Optometry; and Cory Lappin, OD, the Dry Center of Ohio, discuss the “rapid” response seen after treatment with acoltremon for dry eye disease.
Marjan Farid, MD:
Just to sort of complete the circle, because this is sort of the new kid on the block, which is TRYPTYR or acoltremon, and what is the data around that? Cory, you’re familiar with that data really well, so can you tell us a little bit about the FDA studies that got this treatment to approval and what is meaningful?
Then I’d actually like to hear from the other panelists what are the meaningful data points really or outcomes that they measured that you use in clinic? Because I know for example, I don’t do a lot of Schirmer’s testing, but Schirmer’s testing for research can be very valuable to look at improvement in tear production. We’ll start with Cory and then we’ll go through everyone.
Cory Lappin, OD:
Yeah. Obviously, with this, we were looking at natural tear production, and I love, Marjan, how you mentioned Schirmer’s every day. Yeah, not something we’re probably going to be do clinically, but really good way to look at things from that objective study standpoint.
What they were looking at here, the primary endpoint is they’re looking at patients who Schirmer’s testing here, tear production, and they wanted to see what proportion of patients achieved an increase of 10 or more millimeters of wetting on that Schirmer strip at day 14.
Now, what they did is they measured 3 minutes after installation, and they also looked at day 1 all the way up to day 90. But the primary endpoint was day 14, and that was in the COMET-2 and COMET-3 studies. Those were the big pivotal studies, and they found that up to 4 times more patients who were in the actual medication arm versus the vehicle arm achieved that proportion, that 10 or more increase from baseline.
That’s a huge difference. These patients were starting about 6. If you kind of know, we consider normal as about 10, so they were about half of what we’d like to see. The big thing is too then the secondary endpoints, they looked at symptoms, but they also looked at that day 1 and the day 90.
When you look, the results are very similar. It’s actually very fast-acting. You’re still seeing that response on day 1, and it’s sustained through day 90. I know Nate and I have had the opportunity to present this a lot. Those were kind of the big points too, Nate. What from the data really stuck out to you?
Nathan Lighthizer, OD:
Well, I think how rapid it was. Day 14, as you said, was the primary endpoint, but we’re talking day 1 as well. It’s rapid, it’s there immediately. Then you go back to the mechanism of action with TRPM8, as you described so beautifully, it makes sense. We are on day 1 through day 90 in the trial, 90-day trial, we’re producing more natural tears, more basal tears, and that’s a big deal.
You mentioned Schirmer. I wanted to comment going, all right, somebody may be thinking, “Oh, well they put in a Schirmer, that must just be your increasing reflex tears.” No, no, no, no, no. They actually had a phase 3b study. They looked at tear meniscus height. That’s non-invasive, that’s not a tear, that’s not a Schirmer strip in the eye. They looked at lipid concentration, and they found 147% increase in tear meniscus height and a 72% increase in lipid concentration.
We know, go back to the mechanism, it’s stimulating the meibomian glands for more meibum and the goblet cells for more mucin, and the lacrimal gland for more aqueous, more natural tears. The data now proves that from the phase 3b study of an increase in lipid concentration. This is minutes. I believe it was 3 minutes after installation. Again, the OCT tear meniscus height, 147% increase. We know this is not reflex tears, it’s basal natural tears that are so very important.
Karolinne Rocha, MD, PhD:
Again, back to the natural tears. Why is that so important? Of course, lubrication, comfort, the vision, optical properties of the tear film, the refractive index, but healing, as you mentioned, the nutrients supply to the ocular surface. One thing, because some of the studies were presented at ASCRS this year, and one thing that I remember was the fluorescein staining, that we saw changes as early as day 7, and the findings were sustained throughout 90 days, 3 months.
I think this is so important, as we know with some of the other, cyclosporine, lifitegrast, sometimes it will take weeks for us to see improvement in the ocular surface staining. I think to me, it’s really important. Again, back to the mechanism of action, it’s a drug that you can treat, just I would say age-related dry-eyed patients that we see every day. But to your point, Marjan, even more patients with post-LASIK or neurotrophic corneas, some patients autoimmune, because again, increasing that natural tear film production will be key for these patients.
Marjan Farid, MD:
We have so many good therapeutics right now in dry eye disease, and this adds to our armamentarium among the other treatments that we have. I think all of these, as Nate sort of described earlier, finding the right cocktail for the right patient. Certainly improving tear quality by improving all the mucin layer, the meibum layer, as well as the aqueous layer, is for me upstream, treating that, getting the tear film normalized.
Then for patients that need that additional anti-inflammatory component, we have those as well. I think these are all synergistic together. Depending on the type of dry eye disease patient we have, we’re going to see all of these play a role in the management of our dry eye disease patients and ocular surface disease patients.
