Unique clinical trials and novel products of interest currently under investigation for the treatment of dry eye disease.
Cynthia Matossian, MD, FACS: We’re coming toward the end of our presentation. We have a lot in store for you. There are many wonderful and diverse, creative products in the pipeline to help our patients with dry eye disease. Milt, why don’t you get us started with some of the products in the pipeline?
Milton M. Hom, OD, FAAO: The first 1 is from Surface Ophthalmics. As a disclosure, I’m actually in the clinical study for this. It’s phase 2, and it’s interesting because what it’s being used is another steroid but not a steroid you’re familiar with. It’s a steroid that comes from dermatology. It’s betamethasone. If you take a look at all the steroids, according to dermatology, betamethasone is 1 of the most powerful steroids you can use. Now it’s being repurposed in a dry eye drug from Surface. What’s interesting about it is that it has a steroid-sparing agent. It’s called MPA, mycophenolic acid. The steroid sparing enhances the effect of the steroid or the effect of the betamethasone, so the betamethasone is coming in as a very low dose. That’s 1 of the phase 2 drugs in clinical studies.
Cynthia Matossian, MD, FACS: That’s great that you’re participating in the clinical trials. Rahul, do you have any products that you’re excited about that are in the pipeline?
Rahul S. Tonk, MD, MBA: First, it’s incredible that we have such a robust pipeline. This is an incredible time to be in dry eye and ocular surface because we have so much coming. Thank you to our industry partners who are involved in all of this. There are a few that I’ve got my eye on. One is reproxalap, which is entering phase 3 trials. It works against reactive aldehyde species. These are free species implicated in inflammation. What’s very interesting in their phase 3 trial is they’re doing a trial for an indication for dry eye and a trial for an indication for allergy or allergic conjunctivitis.
At the beginning of this talk, we talked about the interplay between the 2. Most of us prescribe for dry eye or allergy. There’s often overlap. I would love to have something on label to help to treat both. Another 1 I’m excited about is PaniDrop. We talked about these novel carriers, these nanocarriers, these nanomicelles that help deliver interesting immunomodulators to the surface. There are several in the pipeline. PaniDrop is just 1 of them—the active ingredient is dihydroorotate dehydrogenase. It’s a mouthful, but this molecule is well recognized in the oncology and rheumatology literature. It’s exciting to have access to it by this nanomicelle technology, by which it can be delivered to the ocular surface. They’re in phase 2b if I’m not mistaken. There are a few others I can talk about if we have time, but those 2 were really interesting.
Cynthia Matossian, MD, FACS: The 2 that I’m also very interested in, besides these, is 1 that’s a keratolytic agent targeting impacted meibum in the meibomian glands. Through this particular chemical product, it dissolves or melts or alters the viscosity by being a keratolytic agent and helping the meibum come out. It’s a chemical and a pharmacologically driven expression of the meibum, as opposed to heat and manual or automatic compression. So that sounds very interesting. One is the nasal spray that stimulates the trigeminal nerve. Through the activation of the lacrimal nerve, it creates a complete tear that has all 3 layers—the lipid, the aqueous, and the mucin—through 1 spray in each nostril to be used twice a day. There’s a lot of very interesting stuff coming down the pike, so be on the lookout. Our toolbox is going to become a huge tool trunk.
Cynthia Matossian, MD, FACS: Kelly, what are you finding exciting in the pipeline?
Kelly K. Nichols, OD, MPH, PhD, FAAO: There’s so much going on in the pipeline right now. You mentioned Oyster Point Pharma’s nasal spray, which is very exciting. But there are a few others that are far along in the FDA process that are worth mentioning. NOV03, which is Novaliq—they licensed it to B&L [Bausch & Lomb]—and it’s specifically for the meibomian glands. It’s a lipid stabilization to help prevent evaporation. It will be interesting to see how this goes through. It’s in its second phase 3 trial, so we should start to see some results relatively soon. Corneal staining and symptoms were their outcome measures that they’re looking at. HanAll Biopharma has a TNF [tumor necrosis factor] receptor fragment, which would bind to the receptor and hope that the release of inflammatory cytokines is reduced. They’ve gone through a phase 3 trial. Although they didn’t meet their outcomes, they’re still working to determine what their next steps are in their program. That’s a Korean company. Lastly, I’ll mention Visomitin SkQ1, another oxidative stress-type product that’s very similar to the 1 Rahul talked about a minute ago and is in a platform very similar. They’re looking at not only front-of-the-eye therapeutic targets with wound healing and inflammation but also some back-of-the-eye with the same compounds formulated slightly differently, and even an oral version of that same compound. So there are quite a few interesting things coming up.
Cynthia Matossian, MD, FACS: The pipeline, as we said, is incredibly robust to the point where we’re getting a little bit of a traffic jam, in a good way. Milt, what other products are exciting you?
Milton M. Hom, OD, FAAO: Novartis is working on lubricin. Lubricin is from David Sullivan of DEWS fame; that’s his drug. It’s in phase 2. We’re working with that 1. What they find is that lubricin is a naturally occurring glycoprotein, and what they found is that in dry eye, it’s actually reduced. By adding lubricin, it’s bringing the dry eye back to homeostasis. Lubricin is essentially a lubricant, so it reduces the friction that you see in the tear film. The other 1 we worked with is Silk Tech Biopharmaceuticals. This is a novel type of approach. It’s the silkworm cocoon. They call it the Bombyx mori silkworm cocoon. You know the silk that you wear? They actually use that. They extract the protein out of that. They found that it’s acting as an anti-inflammatory. What happens is that when you take a look at the inflammatory cascade and the whole immune system, 1 of the chief regulators of the inflammatory cells in the tear film in dry eye is called NF-κB. The silkworm glycoprotein helps regulate that NF-κB, and that affects the inflammatory cells that are in the tear film; therefore, it lowers the whole dry eye profile.
Cynthia Matossian, MD, FACS: Wow, fascinating pathways. Rahul, are there any other products exciting you in our pipeline?
Rahul S. Tonk, MD, MBA: Yeah, I’ll mention 1 that’s interesting. It’s brought by Aerie Pharmaceuticals, and it’s targeting the TRPM8 receptor. What’s interesting is that this is a receptor that can boost tear production, which we mentioned that Oyster Point product coming forward. This space is ripe for innovation in terms of boosting natural tear production. We have a great deal of anti-inflammatories and immunomodulators. There are more coming, but it’s always interesting to see an increase in production. We’ll see how the phase 2b data come out, but it does have some ocular pain relief component to it. If we’re thinking about dry eye and ocular pain as being on a spectrum, that’s a very interesting element for us to look at. We have to be honest. So many of our patients are using over-the-counter products, Visine and Clear Eyes, because they feel good and they have some component of pain relief and that cooling sensation. If we can deliver something that we know is good for them and helps their tear film production, then that’s a win-win.
Transcript edited for clarity.