Veeral Sheth, MD, MBA, FASRS, FACS

New Insight: A Look at Qlosi for Presbyopia with Elad Kedar, MBA

 Elad Kedar's Background and Company Growth

 Transition from Product Development to Team Building

In this episode of New Insight, host Veeral Sheth, MD, MBA, director of clinical research at University Retina and Macula Associates, explored the approval and impending launch of Qlosi (pilocarpine HCL ophthalmic solution) 0.4%, a groundbreaking pharmacologic option for managing 

, with Elad Kedar, MBA, chief executive officer of Orasis Pharmaceuticals.

A condition that affects nearly all adults as they age, presbyopia is characterized by the gradual loss of near vision due to reduced lens elasticity. Sheth and Kedar highlighted the significance of finding non-invasive treatment options for this pervasive issue, given the limitations of traditional solutions like reading glasses or surgical interventions.

In October 2023, the US Food and Drug Administration (FDA) approved Qlosi, a preservative-free, low-dose eye drop for presbyopia, based on strong efficacy, safety, and tolerability data reported in the pivotal Phase 3 NEAR-1 and NEAR-2 clinical trials. On Day 8, patients treated with Qlosi achieved statistically significant ≥3-line gain in distance-corrected near visual acuity (DCNVA) and no loss of ≥1-line in distance visual acuity.

Sheth and Kedar delved into Qlosi’s innovative mechanism of action, emphasizing how it leverages a unique pharmacologic approach to improve near vision. By modulating pupil dynamics, Qlosi enhances the depth of focus, effectively allowing patients to perform near-vision tasks without additional aids. Together, Sheth and Kedar walked through the drug’s clinical development journey, highlighting his journey through the founding of Orasis and the company’s name in Greek, meaning “good vision or sight.”

The discussion included insights into the populations most likely to benefit from Qlosi and the practical considerations for prescribing. Sheth offered a nuanced take on how this therapy could fit into the broader landscape of presbyopia management, addressing questions about patient education, adherence, and expectations.

Sheth also shared his perspective on the potential impact of Qlosi on clinical practice, noting that its ease of use and non-invasive nature could appeal to both patients and providers. He reflected on how treatments like Qlosi are part of a broader trend toward personalized medicine, focusing on solutions that improve the quality of life for aging populations.

This episode concluded with a thoughtful look at future research directions and the impending launch of Qlosi. Expected soon, Kedar expressed an interest in sharing more details on the product and its position in the presbyopia treatment landscape once the drug comes to market.

Every episode of New Insight is available on HCPLive.com. Watch full episodes on our 

 and listen wherever you get your podcasts. Direct all podcast-related inquiries to show producer Connor Iapoce (ciapoce@mjhlifesciences.com) and keep an eye out for more from New Insight!

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In this episode, Veeral Sheth, MD, is joined by the CEO of Orasis Pharmaceuticals to discuss Qlosi, a preservative-free, low-dose eye drop FDA-approved for presbyopia.

Veeral Sheth, MD, MBA discusses the 3 improvements needed for the future of treating patients with geographic atrophy. 

The Future of Geographic Atrophy Treatment

: I think with geographic atrophy, we're in the beginning stages of therapeutics. This is like inning number one of the last game of the World Series. We're finally at a point where we have a therapeutic, that does something, right? After years and years of looking for therapeutics, in clinical trials that just didn't pan out. As a clinician who's been involved in a lot of those clinical trials, I'm very excited about the fact that we got something past the finish line, but we know that this is the first step.

While we have something that's efficacious, it requires a heavy treatment burden, right? We can slow the disease down, but I would love to be able to slow the disease down with maybe a more durable agent, something that doesn't need to be given every month or two. That’s, I think, what patients are going to demand over time. We've seen that with our wet AMD and DME patients, and I think this is no different.

I think that in the future of treating geographic atrophy, we're really going to look for kind of three improvements. One is going to be efficacy – we need agents that are going to further slow down the damage being done, and maybe one day even reverse the damage, but that's even further down the road. But, better efficacy. Right now, we're talking 20 to 30% slowing down, maybe we get to 40 or 50%, maybe we get to 70 or 80%. I think it's something that we have to aim towards.

The second thing is durability. How can we achieve these types of endpoints, but with fewer injections, or maybe even alternate routes? Right now, there are people out there looking at gene therapy as an example. This is a perfect place for gene therapy because you can treat potentially one time and get a prolonged treatment effect from that. That’s one of the things that we're looking at, and potentially something that's not as far down the road.

Then, safety. The third thing we look for is safety. We want to make sure that whatever treatments we continue to push forward that they are as safe, if not safer than whatever kind of bar has been set. Right now the bar has been set by SYFOVRE and IZERVAY. We have got to continue to kind of push those three factors and come up with good solutions for patients. We've done it before with neovascular AMD and DME, and I have no doubt we're going to do that for geographic atrophy as well.

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Veeral Sheth, MD, MBA discusses safety signals reported with the use of therapeutics for geographic atrophy and the importance of real-world datasets. 

Safety of Therapies for Geographic Atrophy

: I think one of the things that's critically important to us as clinicians who want to really help our patients is that with new therapeutics, we really are vigilant and really focused not only on efficacy but on safety as well. And recently we've seen some cases of intraocular inflammation that have been reported with SYFOVRE. And I think it's an important kind of point to address, to discuss. And it’s well known enough where patients are coming in asking about it and bringing in internet articles where they've said, hey, look, I've noticed that there's inflammation about this, and this is in patients that have already been treated with SYFOVRE, and patients that have been thinking about it. And so I think it's an important thing for us to think about, address, talk about, and learn more about as clinicians because we're going to have to understand exactly what's happening. And the scale at which it's happening. At least, at this point, we think that these events are fairly uncommon, I think, one in 10,000 is the rate that's being quoted. And even that rate will be refined further, as we start to see kind of what's happening in the real world as we get a better idea of, hey, how many doses have been administered? And how many of these cases have there been? We're going to further refine what the reality of that is. But right now, like with any new treatment, we're still in that phase where we're trying to understand what's happening, so we as clinicians know where are we going to kind of use these treatments? And how are we going to counsel our patients? And if we do see a case like this, what do we do? As clinicians, I think we're really more vigilant than ever about this kind of stuff. And, and we will be really focused on it. And I think this is where real-world datasets really help. We saw with recently approved agents such as faricimab (Vabysmo), we know that there are real-world datasets coming out, left and right. Truckee was one of the first ones and from those datasets, we got to learn a lot because we started collecting data that wasn't always collected in clinical trials as well. So we're going to learn a lot about efficacy. We're going to learn a lot about safety. And I think that you know, clinicians banding together and kind of coming up with these data points is really really important for us to educate each other as a field.

Veeral Sheth, MD, MBA discusses safety signals reported with the use of approved therapies for geographic atrophy and the importance of real-world datasets.

Veeral Sheth, MD, MBA, discusses how clinicians are beginning to use these therapies and the patient reaction to the availability of treatments for GA.

Patient and Provider Perspective on Therapies for Geographic Atrophy

: We've had SYFOVRE out for a little bit, and IZERVAY fairly recently, we're still trying to figure out who the right patient is for these treatments. And, not just that, but what the right dosing protocol is, what the follow-up is for these patients, and how to continue to refine how we counsel these patients. If there's a question about, what's the consensus, is one treatment preferred over the other? The answer is, it's way too early to tell. I think that we're still just starting to understand how to use these treatments. And I think that will come with real-world data, real-world evidence, and feedback from our patients. That's going to help us refine, not only who we offer this to, but maybe how we offer it, and what that routine is going to end up looking like.

I think we saw that with wet AMD. When we had our first treatments, back in 2005, 2006, we didn't really know how to talk to patients about it, how to treat patients with it, or how it was going to affect our clinic flows. And it took a few years probably to figure out where that would go. And even in wet AMD, we're still refining how we treat, we went from monthly to maybe pro re nata to now the majority of providers using treat-and-extend. Not that that's going to be the exact way we look at this, but I think there's still a lot we're going to learn in how we approach this. Even as an individual physician, if you have a preference for one treatment over another.

I think again, it's way too early to say, maybe a year from now or two years from now, as we continue to collect real-world data, we may be able to answer that question a little better. For the most part, I think patients have been pretty excited about the fact that we can treat this type of macular degeneration. I'll tell you that, I think this year more than any I've had patients proactively asking me about therapies. And I think some of that has to do with the fact that there's direct-to-consumer marketing that's happening, and in a much kind of broader sense than maybe we've seen in the past. I think because of that, there's this awareness of both geographic atrophy as a disease. I mean, people are coming in specifically asking about GA, which, you know, I think that that's very new for us. And then they're coming in knowing about certain therapies and, and that the fact that there is a treatment option, and so they're asking about it.

In general, patients are pretty excited about it, when you start to get into the details with patients, here's what it takes to treat this, and here's what the expectation is, from a treatment standpoint. I would say the enthusiasm is a little more tempered because then reality starts to hit like, oh, boy, I need to come in every month or two and get a shot in the eye. And then that reality starts to set in. And I think we see two groups of patients, we see some that are gung ho, they want to do it, they want to dive right in. And then I see some patients that are a little more reserved, hey, maybe let's see what happens over the next few months, let's get a better idea of what's happening to patients before I jump in. Then maybe there's a third group that is super excited at the very beginning, they start getting treatment.

And then the enthusiasm wears off a little bit when they realize that their vision isn't changing much and I don't know if the impact of the treatment is as obvious to them. And I think that tempers their enthusiasm a little bit. And then, we have to kind of reinforce the rationale of treatment and why we're treating. And most of those patients will continue on at least from what we've seen, will continue on with therapies, but I'm sure some will say I'm tired and I don't want to do it. So again, this kind of all goes back to the fact that it's new. We're still learning. But I think overall, there is excitement, especially from the patient standpoint, because there's an option for the first time that didn't exist with this disease.

Veeral Sheth, MD, MBA, FASRS, FACS

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