Sahar Bedrood, MD, PhD: For the first time in decades, two new class of drugs have been introduced for the treatment of open-angle glaucoma (latanoprostene bunod and netarsudil). How do their mechanisms of action differ from prostaglandins, beta blockers, and carbonic anhydrase inhibitors?
Joseph F. Panarelli, MD: For the first time in a long time we have new classes of medicines to hit the market, and I think it’s very exciting as a glaucoma specialist. We all talk at meetings about how this is really a renaissance in a time of glaucoma. And so to have new medicines to be able to offer our patients is very, very exciting.
Starting first with netarsudil, this is a Rho-kinase inhibitor, and this is one of the newer medicines that actually targets the outflow pathway. And this is really a medicine that’s unique in that none of the other medicines out there on the market actually work at the level of the trabecular meshwork. By inhibiting Rho-kinase, we’re really able to relax some of the actin and myosin contractions. And by relaxing those contractions, we’re able to enhance outflow through the physiologic outflow pathway.
So netarsudil is unique in having this mechanism of action. What’s also particularly appealing about this medicine is that it has other mechanisms of action. We have seen from various studies that it has the potential to lower the episcleral venous pressure (EVP), again something that we often do not see with other medication classes.
Latanoprostene bunod is actually a second new medicine to hit the market, and I think it is sort of a latanoprost on steroids. It’s a new version of a prostaglandin that also has a nitric oxide donating moiety. And what that does is it allows for some smooth muscle relaxation. We do think we get some potential enhanced outflow through the trabecular meshwork. And there may even be some effects on blood flow to the optic nerve. So, once again, it’s nice to have some new medicines that are out there on the market because I think they all fit into our armamentarium somewhere. And I think as clinicians we’re still figuring out exactly how to use these medicines and how to mix them in with our other available agents.
Dr. Bedrood: Briefly comment on the safety and efficacy of latanoprostene bunod and netarsudil.
Dr. Panarelli: So the new medicines that have hit the market, we have seen some of the phase III trials. We have seen the results of the APOLLO and the LUNAR trials, as well as the ROCKETS-1, 2, and 4 trials. And I think what we can safely say is that these medicines work. They have proven noninferiority to our standard topical therapy.
What is unique about the netarsudil/latanoprost combination is this is really one of the first times we actually had a medicine go up against latanoprost alone. And latanoprost we know is one of our bigger guns out there, so it is encouraging to see that we have these new medicines, and it’s nice to see data that does support good efficacy with these different agents.
Dr. Bedrood: How are you personally using these agents in your clinical practice?
Dr. Panarelli: With the two new classes of medicines, many of us are still unsure where to use them in our treatment algorithm. For me, I will often use them if a patient is not doing as well as I’d like on a prostaglandin analogue, and I will use it as sort of switch therapy. I will switch them from either latanoprost to latanoprostene bunod or from latanoprost to a combination of latanoprost and netarsudil.
One special place where I do like these medicines are for my patients with low tension glaucoma. These patients are traditionally some of the hardest to actually lower the IOP to a very low number. And I think what the medicine such as netarsudil where we can lower the EVP, I have found that some of my patients can get down to that single-digit range which is sort of a number I often cannot get with traditional carbonic anhydrase inhibitors, or alpha-2 agonists, or even beta blockers.
For those patients that is a sweet spot for me when it comes to netarsudil. Latanoprostene bunod, while it may not get me quite as low of a pressure, because I don’t really feel it can lower the floor like netarsudil can, I think I may get some improved blood flow. It’s this theoretical benefit that is one of the reasons for some of my patients who are progressing with low tension glaucoma that I might switch them over to that medication.
I actually will occasionally use netarsudil as first-line treatment. Some of my patients who just will not start a prostaglandin analogue. I have several patients who I have discussed the fact that their eye color may change and that they may develop periorbital fat atrophy. And for some of them that’s a big deterrent to starting that medicine.
Similarly, some patients are not too excited about starting a topical beta blocker or they may perhaps be on an oral beta blocker already. So, for these patients, it’s quite nice to start with a medicine such as netarsudil that has once daily dosing. And I think that is a big thing for me. Again, when I’m starting to topical therapy, I like to go with the simplest possible regimen.
I’ve had several patients where I’ve talked about having surgery. We started netarsudil and it’s actually been great in that they’ve gotten to their target IOP without me having to perform a trabeculectomy which is huge for my patients.