44.211.239.1
dgid:
enl:
npi:0
-Advertisement-
-Advertisement-
Presbyopia
Video

Revolutionizing Eye Care: Presbyopia Correcting Drops

Posted on

Mark Dlugoss:

It is estimated that in United States alone there are over 128 million people with presbyopia. That number is expected to increase in additional 73 million people in the years to come, as the number of millennials begin to turn 40. These growing number of presbyopic patients has opened up a market for presbyopia correcting eyedrops, and it is expected to revolutionize how eyecare clinicians will treat this form of refractive era. Hello, this is Mark Dlugoss, Senior Contributing Editor of Ophthalmology 360. Welcome to the Ophthalmic Project, powered by Ophthalmology 360. In today’s ophthalmic project, we sit down with two high level executives of a company that is showing solid clinical results in the development of a presbyopia correcting eye drop. Joining the Ophthalmic project now is Elad Kedar, CEO of Orasis Pharmaceuticals, and Paul Smith, President and Chief Operating Officer. Welcome to the Ophthalmic Project.

Elad Kedar:

Thank you very much. Glad to be here.

Mark Dlugoss:

Okay, good. I know we got a lot to cover, so let’s jump right into it. Let’s begin; and I’ll let you both decide who wants to address this, but let’s begin our discussion with the company itself, Orasis Pharmaceuticals. Can you provide a history of Orasis, its mission, its focus? And what are Orasis’ plans for the next five to 10 years, as an ophthalmic company?

Elad Kedar:

Orasis was established almost seven years ago with really one mission in mind, reshaping vision possibilities for patients. Our first assets, as you mentioned, Mark, earlier, is presbyopia correcting pharmaceutical eyedrops. We’ve also seen the amazing opportunity in the presbyopia segment, and the real need for additional alternatives to reading glasses. And this has been our focus during the past several years. We’ve spent many years in research development, a robust clinical program of our pharmaceutical eyedrops for presbyopia, and we are now already completed our Phase 3 studies. And are now in preparations for our NDA submission, and already started our pre-launch preparations. Throughout those years of research and development, we’ve also built a great team and also great platform, both in the R&D side, and at later years, also on the commercial side. And the team, the platform, are going to be really helpful for us at the later stage after the launch of our first asset to leverage on all of those assets, and basically build the whole portfolio of eyecare. And that is looking 5, 10 years down the road, this is where our focus is going to be.

Mark Dlugoss:

Elad, personally, you have over 20 years in the pharmaceutical industry. Can you provide a short background regarding your experience in the pharmaceutical industry, your business experience? And how it all ties together for you, as you build Orasis into a leading ophthalmic company?

Elad Kedar:

I started my career at Eli Lilly, I worked there for several years. Actually started in finance, moved at one point in time to sales and marketing. After several years in Lilly, I decided that I want to move into a more entrepreneurial path. And since then I’ve been working in several smaller companies, some of them I established myself, and Orasis actually is the third company I’ve been running. I was really fortunate throughout my career to really have a diverse experience within pharma, diverse experience, both in terms of company size, working for big companies such as Eli Lilly, and really learning processes, methodologies. And then in small startups, where I applied everything I learned in those big companies. Diversity also in functions. I started in finance. I moved to sales and marketing and general management. Also from the geographic side. I worked many years in Europe, many years also in Israel, but really focusing on the US market. And finally, I was exposed throughout all my roles to, I would say, almost all stages of the pharma lifecycle. From early stage development through launch, and even into lifecycle management.

Mark Dlugoss:

Paul, I’m going to throw the same question back at you as well. And you’ve been in the ophthalmic business for at least 20 years that I’ve known you. Can you give a little background on your experience, and what you bring to the table here?

Paul Smith:

Yeah, I’m happy to do that, and I appreciate the question. As Elad said, the word that jumped out at me was diversity. And while I’ve had more than 20 years in eyecare, it hasn’t been a linear path. I was fortunate to start my career at Alcon, which was an incredible learning opportunity, incredible company, great people, many of whom continue to work in this space. But I started my role in the field, I carried a bag. I started my career in sales, which really ingrained in me, I think, a focus on the customer. That is something I’ve been able to call upon throughout my entire career in various different roles. While I was at Alcon, I had a chance to work across the pharma business, consumer business. My last several years there, I was on the medical device side of the business, but also had an opportunity, as Elad mentioned, to take on some international assignments.

I spent five years in Latin America, three of them living in Chile. And one of the things that’s interesting is, you wouldn’t imagine in a great big company like Alcon, that you deal with something like resource constraints, or small company challenges that you face in the startup world. But honestly, as you go out into the world and some of these small and medium-sized markets, it’s quite different than what we’ve come to know and expect in maybe the US or Western Europe, or other developed markets. So those were lessons that really served me well.

Ultimately, I think I was bit by the startup bug, and had an opportunity to go into that world for a little over five years. Worked with a company called Tear Lab as we tried to reshape a market around dry eye testing. So had that sort of disruptive technology experience. Spent a couple of years leading US eyecare at Novartis until I joined Orasis, about a year and a half ago. So slightly different path, but I think a lot of transferable learnings, transferable stills. And as I mentioned, it’s really been a privilege to both learn and work and serve this incredible eyecare community within which we operate.

Mark Dlugoss:

I’ve known you for a long time, so it’s good to see you evolving into this space, and a lot of people like yourself, that have done that. Your leadership team has a strong experience in the ophthalmic market. Can both of you elaborate and discuss the individuals you have brought into Orasis? And can you elaborate on how your leadership team, what they have brought to the table for Orasis in developing a quality of ophthalmic products?

Paul Smith:

Yeah, I’m happy to start with some of the recent additions to the team, and I’m sure Elad can build upon this. As he mentioned earlier, really the foundational, some of the initial hires in the company were in the technical function. So if you look at R&D and regulatory, I think as he well said, really where the foundation is, we went into very early stages into clinical, and more recently, we’ve started to expand into commercial and pre-commercial space. And so as I look at the talent that we’ve attracted, I’ll note too, that we’ve hired in little over a year, Julie Speed, who I think you also know, Mark, and Tes Ignacio, who you may also know. They’re both proven professionals in their own respective areas.

Together they bring over 35 years of eyecare experience between them. And obviously that means something. But for me, beyond just the quantity, the amount of experience that anybody brings, it’s about the quality of what that experience is, and what are the shared values. Those are the things that, I think, bind a team together. And I would argue in a small company, they’re even more important. So when you look at our leadership team today, whether it’s across companies big and small, we’ve really attracted some accomplished professionals. Professionals who share that commitment I mentioned earlier, to innovation and a focus on how we best serve our customers.

Mark Dlugoss:

Okay, now let’s move on to Orasis’ drug candidate, CSF-1. It’s a novel presbyopia correcting eye drop. Can you provide some clinical background into CSF-1, its formulations, its mechanism of action, et cetera?

Elad Kedar:

Sure. Mechanism of action is actually pretty well known. It’s pupil constriction, which is creating what we call “pinhole effect,” increase in depth of field. This is what is correcting presbyopia. And for those of us who knows a bit about photography, it’s actually an identical concept to what we’re seeing in a camera. The question is, what’s the innovation of Orasis and CSF-1? And I believe what characterizes our innovation is that we’re able to find that sweet spot. That formula that allows the right level of pupil reduction, not more and not less, that really generates the optimal results. Because we all know about myotic agents, that if the concentration is too low, then you are not getting the desired near-visual acuity improvement. If the concentration is too high, you may have a good near vision, but then it also comes with an impact on your distance vision and your night vision, visual field, and even some others.

And it also, usually, would come with adverse events that are really not desirable, especially in a quality of life category where we are. High concentration myotics are known to cause adverse events such as headache, and brow ache, and eye redness, to name just a few. And from the very beginning of our development, having the patient in mind, we really realized that in order to have a successful product within this space, a successful alternative to reading glasses, we would need to find a product that will represent an optimal balance across efficacy, safety, and comfort.

And we knew that finding that sweet spot, finding that exactly thin line that basically is giving the desired outcome, without coming with the baggage of adverse events, or impact on distance vision, et cetera, that would be the biggest challenge. This is where we put, throughout the years, all the efforts in our development, and eventually we ended up with a formula which is a low-dose pilocarpine. We are focusing on finding the minimal effective dose that will reach all of those outcomes. And together with a multifaceted vehicle, we’re actually able to reach that optimal balance. That is basically the innovation of Orasis.

Mark Dlugoss:

Can you outline some of the clinical characteristics behind CSF-1? And what I mean by that, who’s the ideal patient? What is the proper doses? I think you touched on that a little bit. How long does the drop last in the eye? And can you add a second dose if it’s necessary?

Paul Smith:

Yeah, I’ll take that and build upon Elad’s comment. So the first thing I’ll call out is, as Elad alluded to earlier, we’ve always started with the patient in mind. That’s not necessarily the shortest path or the easiest path, but we thought it was the right one. And we think our market research has continued to reflect that. So we’ve done, over the last few years, extensive market research, thousands of patients. And one of the things that we’ve learned is that what patients value, perhaps above all else, is flexibility, this potential to manage their vision on their terms. And so that means flexibility is a key aspect of what we aim to provide in the CSF-1 formulation.

So whether that is a patient who desires less dependence on reading glasses for a normal working day, or somebody who’s simply looking for a break during certain social occasions, CSF-1 is ultimately a product that’s going to meet them where they are. And so coming to your specific question around dosing mark, our product can indeed be dosed up to twice a day. In our studies, we evaluated visual acuity beyond three hours with a single drop, and up to eight hours following the administration of a second drop. So that flexibility to dose twice a day to get a full day of benefit, is one that our research suggests is something that patients are really going to truly value.

Mark Dlugoss:

Now, in the early clinical trials, CSF-1 demonstrated significant improvements in near vision with a superior safety profile. It also showed solid quality of life improvements with individuals with presbyopia. Can you elaborate more of what Orasis discovered in its early clinical trials?

Elad Kedar:

Sure. The whole essence of our earlier development stage was really to find that optimal formula, and then to fine-tune it. We fine-tuning it in a matter of, what are the final ingredients in the formula? What are their concentrations? And that has really been the focus. As I mentioned earlier, finding that minimal effective dose was one of our critical success factors, and we actually tested various concentrations of pilocarpine until we finalized the 0.4% as the optimal one. And eventually completing the Phase 2B, which was, I believe, by the end of 2019. So about three years ago, we completed Phase 2B. And that after a series of clinical studies that were before, along with the Phase 2B, allowed us to really finalize the formula and lock it. And that is the formula that we have taken into our Phase 3 studies that were just completed earlier this year.

Mark Dlugoss:

Now you mentioned Phase 2B study, and the CSF demonstrated some exceptional near-visual acuity with no reduction in distance or night vision. This study also met the primary endpoint of three line improvements in near vision, which was incredible. Can you provide details behind the whole Phase 2 study? What clinical results you’ve discovered?

Elad Kedar:

So really as you mentioned, the formal endpoint was the formal FDA requirements, three line improvement. And we met that one really successfully. But we took the opportunity in this study, and actually in every other study that we conducted, including the Phase 3 studies that were just completed, we took the opportunity to evaluate all the other endpoints that we knew are going to be critical for the success of the product at a later stage. And again, they all revolve around that concept of efficacy, safety, and comfort. And I could just name few interesting endpoints that again, are not necessarily the formal one needed for FDA, but definitely will be needed once the product is in the market. So starting with efficacy as an example, not only that we tested the three line improvement, we also tested two line improvement as a formal endpoint, because especially for younger presbyopes, two line improvement for many of them is sufficient.

It was always a formal endpoint in all our studies. We also evaluated functional vision. So really, the percentage of people who are getting into the right level of near vision, usually 20/40 or more, is commonly perceived as allowing people to being able to do most of their day-to-day near-vision tasks. So we really evaluated how many patients in our studies, or which percentage, really achieved 20 or 40 or better, both in the steady eye and binocularly, and results there have been really exceptional. Again, not necessarily the formal FDA requirement, but once we checked the box on that one, we also wanted to evaluate others. Functional vision is one of them. I can give you also a couple of examples from safety or tolerability comfort.

We have always tested the patient’s comfort when they’re using our drops. In all our studies, results have been really exceptional. Eye redness, which we mentioned earlier, is one of the adverse events of myotic agents at a higher concentration. In all our studies we’ve seen clearly and consistently that our drop is not creating any effect of eye redness. So these are just few examples of endpoints that complement the formal FDA, and later on, other regulatory agencies’ requirements. We also have added to those many other very important endpoints that will really help us once the product is going to be in the market.

Mark Dlugoss:

Now in April, you announced the clinical results of your two Phase 3 trials, which is Near 1 and Near 2, and you met both primary and secondary endpoints. Can you please outline both these trials and provide what kind of clinical results you were able to deprive from these two studies?

Paul Smith:

Yeah, I’ll take that one, Mark. And the first word that I’ll start with is the word consistency. I think one of the things that we were very thoughtful about, was the design of our Phase 2B. And what we did in Phase 2B, was design a trial that was going to be essentially identical to what we knew we would need to demonstrate in Phase 3. And so in our two Phase 3 studies, the two protocols you mentioned, we were really pleased to announce those results back in April. While we had a really successful Phase 2B, these things are never a given, there’s a reason you do this study. But now with the Phase 2B data, as well as the Near 1 and Near 2 protocols, CSF-1’s been studied in trials comprising more than 700 patients. So really robust clinical program.

And in the Phase 3, as you mentioned, not only did CSF-1 achieve the FDA specified endpoints for a three line vision gain at multiple time points, the product also achieved significance at every other time point we measured. Now those time points were as early as 20 minutes post-dose on day one, all the way out to eight hours. And so when we look at other analyses, some of which Elad mentioned, that have been presented on our Phase 2B data, we will see performance from our Phase 3 in areas like functional vision, which is, as Elad mentioned again, the ability to read at 20/40 or J3 near visual acuity, will show how a large percentage of presbyopes achieved this outcome. And ultimately that’s what it’s about, right? The question is, “I’m dependent on reading glasses, I want to be less dependent. If I take this medication, can I read? Can I functionally get through my day?” And what we saw in these additional analyses was really encouraging in that regard. And those results will be published and presented at upcoming meetings later in the year.

Mark Dlugoss:

It’s good to hear. Up to this point, and you’ve been throughout the trial process, have you come across any adverse effects? And if you did, what were they? And were you able to overcome them, obviously?

Paul Smith:

Yeah, absolutely. So first, again, that notion of starting with the patient in mind has guided our formulation strategy. And so while no product is without some level of adverse events, we saw in the results from our near studies that the overwhelming majority of AEs were mild, transient, and self-resolving. So in our case, the most commonly reported adverse events were headache at 6.8%, installation site pain at 5.8%. And then out of all subjects evaluated, only 2.6% of them reported moderate treatment-related adverse events. Everything else was mild. So really encouraging results, and we believe it’s really important, again, in this category that is really a lifestyle category. Patients are looking to trade what they deem to be an inconvenience in their readers, and what they don’t want, is a trade-off that brings additional discomfort or headaches, both figurative and literal, in this case. So really pleased with those results.

Mark Dlugoss:

That’s good. Now with CSF-1 reaching the milestones that you’ve reached so far, what are the next steps for Orasis, as the company moves closer to an NDA submission to the FDA?

Elad Kedar:

Yeah, I can take that one. So first and foremost, obviously making sure that we are well prepared for the NDA submission, and we are really at pretty advanced stage there. And getting the product approved is going to be our focus during the next 12 months or so. Concurrently, we already started, and will continue and accelerate the pre-launch activities, as we want to make sure that we are having a state-of-the-art launch of this product. Looking at the longer term is continuing and leveraging on our team, our platform, to build a portfolio of additional products in eyecare. But first things first, the key topic for the next 12 to 24 months is really making sure we are getting the approval, and successfully launching our presbyopia assets.

Mark Dlugoss:

So when do you expect to have your NDA submitted to the FDA?

Elad Kedar:

We are planning to do it at the second part of this year already, so hopefully the approval will come sometime next year.

Mark Dlugoss:

Great. When one looks at the new market of presbyopia correcting drops, what makes CSF-1 clinically different from the other presbyopia drops that are in development?

Paul Smith:

Yeah, happy to take that. And again, kind of speaking back to our Phase 3 data. When we released that data back in April, there was a lot of interest, as you would anticipate, some real excitement about the results and just the potential to offer patients an other alternative. Really it’s about having more options in the armamentarium for providers. But one of the key features of CSF-1 that has emerged, what we’re hearing as potentially preferred by many providers as a place to start their presbyopia patients, is the minimal effective dose. Elad talked about it earlier, that minimal effective dose of CSF-1 at 0.4% is really a distinguishing characteristic. And other products being studied have taken a different approach. And again, I’ve said this throughout my career, there’s no product that is right for everyone.

So I’m sure that there’s a ton of space with, as you mentioned in the opening mark, over 120 million presbyopes in the US. We do see, we do hear that there’s really significant potential for CSF-1 to be the place to start for more patients. Other products are being studied in the range of glaucoma concentrations where they were used, medically, in the past, in a lifestyle category. Again, as I mentioned, patients are looking for fewer trade-offs, and we believe that balance that CSF-1 strikes across efficacy, safety, and comfort, is going to help certainly hit the mark for many of them.

Mark Dlugoss:

Let’s talk about the market in general. As you know Vuity by Allergan’s already out there, and you got maybe five or six others in development, so it’s becoming a growing segment in ophthalmology. So how do you guys view the market of presbyopia drugs? And what’s the potential moving forward?

Paul Smith:

So first it’s clear that it’s massive. I think just the sheer numbers are something like we haven’t seen, and you don’t often see in healthcare, in any therapeutic area. So with that many presbyopes in the US, there’s certainly going to be room for many companies to participate, and obviously, contribute to growing the category. One of the things that’s interesting about presbyopes, however, there are data that show that 87% of emmetropic or Plano-presbyopes are patients for whom, they don’t have any other sort of refractive error. 87% of them don’t currently see an eyecare provider. So you have basically half of your addressable market that has no relationship. So across optometry and ophthalmology, we expect that this new treatment modality will bring more patients into a continuum of care.

So that’s a good thing from a general public health perspective. But as it relates to where drops fit in the overall care continuum, we think of it as an end. It’s a compliment to what patients and providers are already doing today to manage their vision. And so again, the notion of flexibility is one that we see really resonates with these stakeholders. Elad mentioned this in the data, early presbyopes, in particular, desire less dependence on readers, and our data and our market research continues to support that. So CSF-1, in this constellation of options, these various modalities, is really going to help patients go on with their daily activities without the burden of keeping up with readers for every moment that matters to them.

Mark Dlugoss:

That’s good. How do you see the market globally?

Paul Smith:

Again, the word is still massive. I know we’ve talked about the 120 million in the US. There’s another-

Mark Dlugoss:

That’s a lot of people. It’s only part of the world.

Paul Smith:

There’s another 1.8 billion when you get outside. So you’re talking about nearly 2 billion patients in the addressable market around the world. So while the US is certainly where we are starting, we’re advancing things in Europe. We’re looking at the broader market. Again, we’ve talked about other regions, Asia, Latin America, and we see significant interest comes to us on a regular basis, almost daily, through our website. Folks certainly hear the news, and we live in a relatively small world, and eyecare is an even smaller community within that small world. So certainly a lot of interest in discussion, so significant potential outside the US as well.

Mark Dlugoss:

So has Orasis continued its clinical trials elsewhere, or are we still focusing on United States?

Paul Smith:

Right now we’re focused on the US, and we’re in conversations with the health authorities in Europe. And together we’ll decide what part of our data is applicable toward a filing with AMA. It may be all of it, it may be some of it, but those are conversations that are taking place currently

Mark Dlugoss:

Now with Vuity by Allergan already approved and in the market, where does CFS-1 fit in this potentially large market of presbyopia correcting eyedrops? I mean, like you said, and Paul, you summed it up, but I might step forward. You said there’s room for a lot of people, because you got over 1 billion people with presbyopia worldwide.

Paul Smith:

Yeah, I think what we’ve learned, especially anytime you’re building a new category, that learning and education are critical pre-launch, certainly at the outset. There’s no substitute for real-world experience. And so, one of the things that we’ve seen over the last several months, approximately nine months now since this category was established with the FDA’s first approval, is that there’s a huge opportunity, a huge need for education, and it’s certainly continuing. We’re certainly supporting medical education ourselves, but really as you come into this new category, I think there are a lot of questions. Even our closest advisors who are thought leaders in this category, they don’t have all the answers, in fact, they’re helping us to ask better questions. What are the types of things that we should be seeking to understand from patients? What’s the language that we should be using to set the right expectation?

And so those things are, we think, critical to shaping this category. Everything from how each of these products performs, there’s certainly going to be differences among them, setting the right expectations around patient selection. We’ve seen this in other categories over the last 20 years, whether it’s multifocal contact lenses or presbyopia correcting IOLs, there’s certainly learnings that we can leverage from those other areas. And we are leveraging them, just to help patients understand what are you likely to experience? At what point will you see a benefit?

And then you can assess whether or not this is the right solution for you. Again, I think one of the nice things that we can count on, that aren’t always the case, and other presbyopia modalities is that, again, this is flexible. Patients can figure out how it works for them, when it works for them. And really, we think setting that expectation appropriately for both doctors and patients is going to set more of them up to have a positive experience. So as we look at the market, as it’s building out there currently, we continue to be very encouraged by the level of patient demand. And we’ll continue to get smarter. Every day is an opportunity to learn, and we continue to do so, and we’ll leverage all that toward our own launch in the coming months.

Mark Dlugoss:

Now, as you move towards marketing CSF-1, and you notice that Vuity is out there already, what has the team at Orasis learned regarding what to do and what not to do, when you bring CSF-1 to market?

Paul Smith:

Yeah, I think, again, going first is always both exciting, and it represents a unique challenge. And I think that’s what we’re seeing in the market. This really neat space that we work in, where the cadence of innovation is a lot faster than maybe you see in other categories. I think we’ve had the good fortune, I certainly consider myself among those who’ve had the good fortune to participate in numerous product launches over the last 20 years. And I think some of the fundamentals still apply here. We need to listen to the voice of the customer, the voice of the patient, the voice of the provider. They want to understand how is this product going to work in my hands? What’s the amount of work that’s required? Again, as I mentioned earlier, what’s the language? Who are the patients that are most likely to benefit? And at least increase the likelihood that we have success earlier on.

So all of those things are, I think, commonalities among launches. Certainly when you’re building a category. And we’re taking, as I mentioned, careful notes. So this is something that is really dynamic and even though we’ve done tons of market research over the last few years, it’s something we will continue to do. Because the way that patients felt about their near vision in 2018, if we go back to our original research, this was in a pre pandemic world, is different than they feel about it now. Many of them spent two years communicating like we are now, staring into a camera, and have a different appreciation for what they want their near vision to be. And so we continue to go back and ask them and make sure we’re having the right conversation, make sure we’re developing the right education. And then, again, in partnership with providers, making sure that the doctors, their staff, their practices, are well equipped to receive them when the time comes.

Mark Dlugoss:

And now that CSF-1 is moving toward an NDA filing, and with the FDA potential approval, are there other programs that Orasis Pharmaceuticals is planning, that you can share with the viewers?

Elad Kedar:

There are actually few medical education programs that we’ve sponsored, that are taking place in the second part of this year. While presbyopia is obviously not a new category, we all kind of learning on how to best educate physicians and later on, also patients, on what’s the best way to use this new category, and to basically optimize visions through this new alternative.

Mark Dlugoss:

We’ve covered a lot of information today. Is there anything that you both feel we have missed, regarding CSF-1 or Orasis Pharmaceuticals, that you may feel is important for our viewers to know?

Elad Kedar:

Yeah, I agree. I think we had a great discussion and we covered really all the main areas that the company’s focusing on these days. And hopefully you’ve seen the company is really taking the launch, or even before that, the NDA submission, later on the launch, very seriously. We are really excited to be the next to launch in this potentially amazing category, and we just look forward to share more as we are getting closer to launch and beyond.

Mark Dlugoss:

Great. That sounds great. Well, that concludes today’s Ophthalmic Project podcast. I want to thank Elad Kedar and Paul Smith for spending some time with the Ophthalmic Project, discussing Orasis’ Pharmaceuticals entry into the presbyopia correction market. I also want to thank you for watching. And I hope to catch you on the next edition of The Ophthalmic Project powered by Ophthalmology 360. Have a great day.

-Advertisement-
-Advertisement-
-Advertisement-
-Advertisement-
-Advertisement-
-Advertisement-