Following the American Academy of Optometry’s (AAO) annual meeting in Anaheim, California, Optometric Management caught up with Nora Lee Cothran, OD, FAAO, who presented phase 3 data from the US subpopulation of the DENALI trial of NCX-470 for the treatment of glaucoma.

This transcript has been lightly edited for clarity.

My name is Nora Lee Cothran. I'm a consultative optometrist and I specialize in glaucoma and neurological eye disease at the Eye Institute of West Florida.

Can you give a brief overview of the trial, its findings, and the mechanism of NCX-470?

The DENALI trial was a randomized, double-masked, active controlled parallel group study that was conducted at 90 sites worldwide, including 65 sites within the United States. The study paper that I presented at this year’s American Academy of Optometry meeting focused on the US subpopulation. The goal of the study was to investigate mean intraocular pressure (IOP) reduction of NCX-470, which is bimatoprost grenod 0.1%, vs latanoprost 0.005% in subjects with primary open angle glaucoma or ocular hypertension.

Within the US subpopulation, 549 patients were washed out of their previous drugs over a period of time, depending on which drugs they were previously on for their glaucoma, and they were randomized 1-to-1, either into the investigative arm or the control arm, which was latanoprost. This is one of the first US Food and Drug Administration (FDA) glaucoma clinical trials that used latanoprost as the comparator vs timolol.

These patients were followed forward in time, and IOPs were measured at week 2, week 6, and month 3 at 8:00 AM and 4:00 PM. The primary endpoint was noninferiority to latanoprost, and it was met at all timepoints throughout the trial for NCX-470 bimatoprost grenod. Statistically significant changes in IOP were observed at 3 out of the 6 time points.

NCX-470, bimatoprost grenod 0.1%, is a nitric oxide-donating bimatoprost. This is a single molecule that has dual mechanisms of action. The prostaglandin analog works within the uveoscleral outflow; the nontraditional pathway. The nitric oxide component that's donated once the molecule enters the anterior chamber actively works within the trabecular meshwork in the conventional outflow.

How should clinicians interpret the magnitude of the IOP differences observed in DENALI? What might a difference of that size mean clinically for a patient who has glaucoma or ocular hypertension?

The DENALI clinical trial demonstrated that NCX-470 bimatoprost grenod had robust and efficacious IOP lowering on average 8.1 mmHg to 10.1 mmHg in the investigative arm. Bimatoprost grenod was well tolerated and there were no serious treatment-related adverse events throughout the clinical study.

I always get asked if statistical relevance actually means clinical significance, and that's an excellent question. The answer is yes in this particular case. The medication met the primary endpoint across all the time points, but IOP was also lower at all time points and was statistically significant at 3 out of 6 of those. We know from the early manifest glaucoma trial, one of the landmark trials in glaucoma, that for each mmHg that we can lower a patient's IOP in the first 3 months, patients are insulated by 10% per mmHg against future field loss. And so, when I’m asked, “Does a few millimeters of mercury matter?” I say it absolutely does when this molecule is compared to latanoprost alone.

Additionally, we've never had a therapeutic molecule in our armamentarium that has the possibility of lowering an IOP 10 mmHg. Within the clinical trial, there were obviously patients who were on either ends of the 8.1 mmHg to 10.1 mmHg average, but the AAO treatment guidelines for starting a patient who is newly diagnosed on glaucoma medication is to lower the IOP 20% to 30%. Within each of the time points throughout this clinical trial, the AAO guidelines were met or exceeded by bimatoprost grenod.

The safety and efficacy data for NCX-470 bimatoprost grenod was consistent with the MontBlanc phase 3 data, which were submitted to the FDA for a new drug authorization.

What else do you hope clinicians take away from the presentation you gave at Academy?

I hope my colleagues walked away from the presentation or even their time at the Academy and feel or recognize that we're in the golden age of glaucoma. Never in the history of humankind have we had so many options to treat this disease. Our understanding of the disease is greater. We understand so much more about the pathophysiology. We now have treatments that actually target the trabecular meshwork, which is the fundamental source of dysfunction in most types of glaucoma. And optometry is the first line of defense.

Most of these patients are sitting within our optometric offices and, as a clinician, you're in the driver's seat. You get to choose what's best for the patient and help guide them. We know if the disease goes unmanaged or is not actively managed, the patient is usually unaware of how bad things can really get.

But as those of us on the front lines of managing the disease, having as many possibilities for treatment in the toolbox allows you, as the doctor, to do the doctoring and choose what's best for your patient to get them safer. I think about it like this: The patient's out in a storm and we're going to put a life jacket on them. You could put some arm floats on them, or you could zip them up in a good life jacket. We don't know when the storm's coming or how bad it's going to be, but you, as the doctor, have the ability to insulate your patient and treat them earlier.

So in this golden age of glaucoma, I just challenge my colleagues to level up your glaucoma game. Even if you're not apt to prescribe a newer molecule first line, consider switching to a dual mechanism if you have patients who are progressing. These days, we have a lot to offer for our patients that we didn't have in the past.