[creativ_pullleft colour=”light-gray” colour_custom=”” text=”Episode 074″]
Glaucoma once might have been a boring or sleepy sub-specialty of ophthalmology, but recent technical advances and significant bets placed by large strategics including Alcon’s planned ac-quisition of Transcend has injected the sector with enthusiasm and energy. OIS Podcast, in our new KOL Corner features, talks with leading glaucoma specialists about where the field is headed.
Jan Brady:Well, all I hear all day long at school is how great Marsha is at this or how wonderful Marsha did that. Marsha, Marsha, Marsha.
Tom Salemi: Hi, everyone, welcome back to the OIS Podcast. Don’t worry, we have not been pirated by TV land. I just wanted to introduce this Podcast with that very famous scene from the much beloved Brady Bunch because this week we’re focusing on glaucoma. This is our first what are called KOL Corner Podcast. We’re going to be speaking with KOLs in ophthalmology on a regular basis going forward, compiling their thoughts and sentiments, and bringing them all together into this forum where we can look forward at some of the promising drugs and devices that are being developed, but also perhaps talk about some of the challenges that are being faced by practitioners in each subspecialty. So today we’re fortunately talking about glaucoma for a few reasons. First, January was Glaucoma Awareness Month, so it clearly was on the minds of many. We had the Glaucoma 360 panel, 360 Conference, rather, at the start of this month in San Francisco, which was a wild success, so we hear. And finally, last week, of course, Alcon made its bid to acquire Transcend, which really heats up the whole MIGS space. So this is a great opportunity to talk to some leaders in glaucoma about this specialty, which in the words of one of the folks we talked to, was always the – had been traditionally the boring stepsister of ophthalmology. It was an area that did not get a lot of attention from innovators or even from clinicians in some cases. But that has changed, and that’s why we led with the Brady Bunch opening, and I know Marsha and Jan are actual sisters, not stepsisters. But it was a parallel I didn’t want to miss. We’ll talk to a few leading glaucoma specialists about Glaucoma 360 in a little bit, but first let’s focus on the news of last week. Transcend, based in Menlo Park, has developed the CyPass Microstent. It’s a MIGS device that’s implanted in the anterior segment of the eye, and it helps create a drain for the aqueous fluid into the suprachoroidal space in the eye. Last fall, as we reported at OIS, Transcend submitted to the FDA its positive two year results from the Compass pivotal clinical trial. So it got that PMA moving down the track. Well, according to Wendy Hutton of Canaan Partners, one of the investors in Transcend, that big of good news drew a lot of interest from acquirers, and understandably, it presented an opportunity for Transcend’s executives and investors to find the right partner to commercialize the CyPass and to get it into the hands of surgeons or specialists and into the eyes of glaucoma patients as they undergo cataract surgery. The terms of the offer are confidential. They haven’t been disclosed. But in an email, Wendy wasn’t available to be interviewed for the Podcast, but in an email she said that Transcend is “very pleased with such a favorable outcome.” So it was likely generous, as was the AqueSys acquisition by Allergan last fall, which started with the $300 million upfront payment. So what does this mean for the MIGS space? I talked to Liev Abraham. She’s the senior analyst at Citi’s Equity Research Group. She covers specialty pharma. She was at OIS last fall. She helped with one of our breakfast breakout sessions. And she does not cover Alcon, so she can’t speak directly to the Transcend acquisition, but she does cover Allergan, which acquired AqueSys, and it provides a pretty good model for what we’re talking about here. And I asked Liev how large an opportunity she sees MIGS being for Allergan with the AqueSys device in house, and here’s what she said.
Liev Abraham: I put it down conservatively at around $200 million in sales. But it could certainly exceed that, depending on how rapidly it’s adopted and how many other players are in the space. And I’m aware of the acquisition of Transcend last week. So I think that’s a pretty conservative estimate. But overall it fits in with the company strategy and in the industry generally moving toward minimally invasive procedures or longer duration therapies to mitigate some of the issues of compliance. The one thing that’s interesting to note here is that this is a very attractive proposition for physicians because the amount of time that they spend on the procedure is very low compared to trabeculectomy, and therefore they can do more procedures in a day, and the financial incentivization is high. So there is a very real possibility that adoption could be rapid and the peak sales opportunity could be higher than what we’ve published.
TS: If Liev Abraham is right, it’ll come down to the doctors. This gives them a tool to use in glaucoma treatment. This presents an opportunity for them to treat more patients than they’ve currently treated. So we talked to some of the leading, perhaps the leading specialists in the field, one of them Kuldev Singh, the Professor of Ophthalmology and the Director of Glaucoma Services at Stanford, says that as far as looking at treatments for glaucoma, we’re really just at the tip of the iceberg. But he sees the Transcend deal as being a positive indicator, and perhaps a sign of hope for innovators going forward to create new treatments for glaucoma.
Kuldev Singh: I think it’s exciting. It’s great that Alcon has invested in Transcend because it shows validation that MIGS is for real. And I think this is going to help patients, and it’s good for both companies. And more importantly, I think it’s good for the field. It’s good for the other people innovating in glaucoma know that there is an interest in taking these technologies forward, innovating to help patients. And whenever you see this type of a deal being announced, there are only good things that can come out of it for the profession. And I would imagine that everybody is excited about this. And I think you’ll see more activity in the next year or two in the glaucoma surgical space. So I’m very positive about this, and everything I’ve heard has been positive from others. You know, we had the Allergan acquisition of AqueSys recently as well. So two big deals in the space of less than a year, actually about 6 months. And this is just tremendous validation for our field and great news for patients that big companies are investing in ophthalmology. And specifically in glaucoma, I might add.
TS: But what sort of dynamic is shaping up here? Is this going to be a horse race? Is this going to be a battle for the MIGS market? Liev Abraham says the pie is big, so there’s a lot of pie to go around to different MIGS players. And there are more to come. If you go to OIS.net and search MIGS, you’ll see presentations from many startups in the MIGS space. But I asked Dr. Rick Lewis. He’s got a great perspective on the space. He’s been the past president of the American Glaucoma Society and of ASCRS, so he’s got a great point of view on where these devices will fit in the actual practice of medicine. And I asked him are we looking at a fight, are we looking at a horse race for the MIGS market? And here’s what he said.
Rick Lewis: There is. And it’s interesting. You know, it’s a horse race in some ways, and not in others. The MIGS space has always been defined by the target tissue. So for example, the eye stent has been directed at the canal space. Transcend has been directed at the suprachoroidal space, and AqueSys with the Zen procedure is in the subconjunctival space. So what that implies is that we have these safer procedures, but they’re directed at different types of glaucoma. And maybe the race will heat up when they begin to cross over and show that these different mechanisms can work in different spaces. But right now, they’re really defined by their target tissue.
TS: That’s a great distinction. I guess I’ve seen them as competitors. It’s easy to do that. They’re all – have similar products in the same area. But at this point, there really is very little cross over between the three?
RL: Well, at this point, at least by FDA labeling will indicate that the canal space is limited to open end glaucoma; the Zen perhaps may be restricted to more advanced disease. It’s just thinking by labeling. Now that of course doesn’t mean a lot when it actually gets to the market – the market the doctors will use it for whatever they indicated it for. That’s really exciting. And all three of these companies get on the market, it’ll be fascinating to see what types of diseases it will treat. Will it hopefully will treat both primary and secondary glaucomas in some of the more advanced problems. And that’s what we’re all hoping for in glaucoma, despite the labeling.
TS: So that’s an interesting perspective, and it’s obviously I hadn’t thought about, the fact that these devices can really coexist, at least initially until things play out. I spoke to Dr. Andrew Iwach. He oversaw and created Glaucoma 360, and we’ll talk to him about that in a little bit. But regarding MIGS and Transcend and all the other players, Glaukos of course, I asked him sort of how will these entities coexist, and who is likely or what is likely to help determine the winners or at least the leaders in this space. Let’s have a listen.
Andrew Iwach: It’ll depend on the patient. I think that as we’re still relatively early in the process, glaucoma is a chronic, long term disease. And so when we look at 6-month data or one-year data or even 2-year data, that’s very, very important. But ultimately, we’re looking at patients who are living longer, and we need solutions that’ll last ten years, 15 years, 20 years. Can we repeat it? Are there any complications that we didn’t foresee that may occur? So I think that in some patients, an iStent at the time of cataract surgery might be the excellent choice. On the other hand, the new Transcend devices also look very encouraging. But again, we’re going to just have to get it out in the field, get some more longer term data to see how they compare. We’re also – there’s a pressure level that you’re going to want to achieve may influence which of these technologies you go to. If you need a really, really low pressure, then you may want to look at something like the AqueSys device, where you’re trading off lower pressures, you’ll have hopefully a very nice low bleb. If you need just a tweaking, maybe an iStent would be – so I think it’s going to be one size does not fit all. As we go further and get more data, we’ll get a better sense of how these different technologies work long term. I think there’s going to be a place for all of them, and it’s just going to be a matter of then fine tuning for that patient. But as a surgeon who uses these, boy do I love having the options. Being able to sit down with patients and say, you know, we just don’t have a trabeculectomy. We have now a number of options. Let’s talk about your cataract, let’s talk about – in fact, that’s one of the things I tell patients when they first come in. You know, we do a full history. You know, we’re physicians; we’re ophthalmologists, and I’ll say, you know, you look healthy, you sound healthy, I think you’re going to be around for a while. If you know something I don’t, we can save each other a lot of time because glaucoma is not going to bother you for 6 months, right? But it’s this ability to really customize care in a more efficient way with these newer diagnostics helping us to make the recommendations for the patients. I’ve never had as much enjoyment in helping patients. It’s really an exciting time being – helping patients with glaucoma.
TS: So that’s our breakdown of the Alcon-Transcend deal, where it fits in the MIGS space, how it will deal with others in the space, including Allergan/AqueSys, or Glaukos, which of course is the pioneer in this space, and is really blazing a trail. So we’ll focus now on the Glaucoma 360 event, which was held in San Francisco. It goes on for three days and it looks at the both existing treatments and new treatments coming down the pike. I talked again to Dr. Singh about the event, asked him what were some of the highlights, and if he was surprised by anything presented, either early or late stage over those three days. Here’s what he said.
Kuldev Singh: Well, I think there’s definitely no major surprises. I’ve been following several of the innovative approaches quite carefully. But there – people are making progress, certainly I’m happy to say that Aerie is continuing to do well moving forward with their phase 3 program. I was pleased to see that there are several drug delivery companies that have external and internal approaches that are doing exciting work. ForSight Vision5, Ocular Therapeutics. So for example, have external technologies that would be their Helios Ring, so ForSight, and the punctal plug approach with Ocular Therapeutics. I think it’s nice to see, and phase 2 studies prove that you can lower intraocular pressure with external drug delivery. There are also several companies looking at intraocular, intracameral or posterior segment drug delivery for glaucoma as well. And you know, overall I think that there’s progress being made both in terms of novel molecular entities as well as drug delivery. On the surgical side I think it’s very, very exciting. I think there’ll be several MIGS devices on the market, and I think there’s room for several devices but I think the different devices have different approaches that will benefit particular patients. I don’t think one device will be perfect for every single patient. But I do think there’s room for multiple devices to span that category.
TS: So we hear a lot of familiar names in that account of what he heard, what Dr. Singh heard at Glaucoma 360: ForSight, Ocular Therapeutics. We’ve seen them at OIS and happy to hear they continue to make progress. And I’m sure we’ll hear more about that at a future OIS. I also talked with Dr. Lewis about Glaucoma 360. He had delivered the Fredrick Sutro Memorial Lecture, the keynote address there. And in his talk, he gave an account of the many years he has spent working with glaucoma startups, with glaucoma companies about developing new products and new treatments. This is going on 30 years of consulting in glaucoma. And in his keynote, he really wanted to focus on the good, the bad, and he says, the ugly of some of the projects that he’s worked with.
Rick Lewis: Well, I had the honor of giving the Sutro Lecture, which is the main lecture of that meeting. And this was focused on my 30 years of consulting in glaucoma. And I pointed out the good, the bad and the ugly of some of the things that I’ve been involved with, some of which were very helpful for patients, and some of which were complete failures. And I think we have to learn from our mistakes in all aspects of this, both in drug development as well as the launching of the products. And I pointed out a number of problems and some successes in getting clinicians to change behavior and also in helping our patients. So it was a lot of fun for me to be able to put this together. I was only given 30 minutes; I probably could have spoken for two hours because there’s a lot of good, bad and ugly along the way. But all in all, it’s been very, very good, and a big honor for me to give that talk.
TS: Can you share one or two ugly developments for us? You’re right, it’s not something that we often do in this industry, look at the growing pains.
RL: Well, you know, one of the ones was a launch of a product. Well it was originally an Israeli company, Kolapinol that launched the Express. And they contracted with Ciba to launch it in the US. This was about a little over ten years ago. Ciba really didn’t have much experience in the surgical field at the time that they hired some sales reps who then had a certification program for the Express device at the American Academy meeting site. And so in about a 5 to 10-minute session, you were able to take your device, which had an injector, inject a few into a pig eye, and then they gave you a – printed out a certification. So people went home and felt they were experts in glaucoma surgery. And it resulted in a series of complications – choroidal hemorrhages and infections and bleeding – because they really didn’t spend the time to really teach the surgeon how to do it. And it led to the – they pulled the device off the market, and had to relaunch it in a different way. It took a couple years to relaunch it. Ultimately, the Express turned out to be a good device, and Alcon acquired the Express a few years ago. But it was an example of very, very nearsighted approach to launching a clinical product. The reverse of that, I think, was what Glaukos did with the iStent, with how they very carefully selected surgeons who were very, very competent. They actually sent many of them to Armenia to do additional training off site. They had their reps well trained in the OR, had them do a certain number of cases under direct supervision before they were given the green light to go. And I think that’s the two extremes of a surgical launch. And very important lesson that was learned. And then of course there’s other lessons that were learned, products that did excellent in clinical trials, and when they got in the market, production changes caused some severe complications. So again, I could have talked for hours about some of the things that happened here. And I touched on a few of the more noteworthy ones that I think hopefully won’t happen again.
TS: And finally, I’ll go back to Dr. Iwach. Of course, he again created and leads Glaucoma 360. I asked him the question that I asked Drs. Singh and Lewis as well, and we’ll have the full interviews with those physicians in upcoming OIS Podcasts, so there’s a lot of good material there. I’m sure you’ll enjoy those conversations. But the question I asked to the three, and Dr. Iwach will answer in this case, is what is driving this surge of innovation in glaucoma today. Why is this all coming together at this time? Is it just a confluence of technologies that are making this progress possible? Is it patient demand? Is it something else? So Dr. Iwach had very interesting answers, as did Drs. Lewis and Singh, but let’s have a listen as to what he sees as the reasons behind this surge in progress in glaucoma treatments.
Andrew Iwach: Well, certainly the market is increasing. As the population ages, the incidence and prevalence of glaucoma increases. But also, the new products that we have, the new solutions that we have that are now available, for example, the iStent. Well, those have been worked on for many years. And as many know, the process can be circuitous and prolonged. But there’s a real need. Currently, our quote state of the art techniques in helping patients unfortunately have, at a minimum, inconvenience, and often can give symptoms and have potential complications. The reality is that most patients with glaucoma don’t know they have the disease. In fact, that’s why we spend a lot of effort in looking or screening for it. Now, if you take a patient who has no symptoms, and we know that if we don’t do something, over time they will lose vision, and we try to help them in intervening, some of our current interventions – in fact, we’ll take a patient with no symptoms, and give them symptoms. And so there is a real need for finding better solutions, ways to help these patients while at the same time minimizing the impact on their quality of life today. And that is a true need, and fortunately industry and researchers are addressing it, and Glaucoma 360 has turned to be a great platform to share the new developments.
TS: Is glaucoma in your mind merely catching up to some of the other subspecialties within ophthalmology?
AI: I think there is some cross-pollination where there are some developments in other areas. There’s several points where there are real breakthroughs. For examples, on the pharmacology side with prostaglandin analogs, which were approved back in 1996, that really change the spectrum of how we were doing things. When newer lasers were brought in, such as the new selective laser trabeculoplasty, that had an impact. And how we know it had an impact is if you look at Medicare data, you can clearly see that the number of the more invasive filtering surgeries, the standard trabeculectomies have gradually dropped off, and the timing lines up with, for example, when the prostaglandin analogs were introduced, as well as the increased utilization of lasers. So the technology has been introduced. It takes a bit of time till people get comfortable with it, but there’s no question that the impact on patient care is real. And patients are benefitting from it. For example, now with the introduction of the iStent over the past few years, this has been an important new tool to help patients. And the focus has to be not only are we trying to keep them seeing, which is of course very important, but we need to also try to keep them happy; that is try to minimize the impact of our interventions on their quality of life today. At Glaucoma 360 at New Horizons, we had the opportunity to have some input from the FDA, and I was pleased to hear that there appears to be a new initiative to, when evaluating new interventions, not only looking at how successful they are, not only looking at their complication rate, but there’s an active process being set up to try to incorporate patient input, how they perceive the procedure or intervention. I think that’s really important, particularly in a disease like glaucoma, where if we don’t treat them, of course they can go blind. So we have to do something. But at the same time, can we find ways to protect their vision and at the same time not make them miserable in the meantime?
TS: All right, well that is our wrap on our first KOL Corner on your OIS Podcast. I hope you enjoyed it. If you have any feedback on this or any Podcasts or any of our OIS content, feel free to shoot me an email. My email is email@example.com. Healthegy is spelled like the world health followed by the letters EGY. So firstname.lastname@example.org. This is clearly not going to be our last focus on glaucoma. It’s a dynamic space, and it’s one that continues to grow and advance. So I’m pretty sure we’ll the talking to glaucoma specialists again sometime in the future. It’s no longer Jan Brady; it is now a total Marsha Brady subspecialty. It’s all about glaucoma, glaucoma, glaucoma. Thank you, Drs. Kuldev Singh, Rick Lewis and Andrew Iwach for joining us today, for talking about the Transcend deal and sharing your experience from Glaucoma 360. Thank you, Liev Abraham for your thoughts on the MIGS space. It’s always great to have you on the Podcast. And thank you, our listeners for joining in. And don’t forget to go to OIS.net. it’s revamped, it’s new, a lot of great content up there. And you can register for the upcoming OIS@ASCRS. It’ll be on May 5. So please go there. Our co-chairs, Emmett Cunningham, Gil Kliman, and Bill Link have been working hard on the agenda. It looks terrific. And the early registration numbers are very strong. We had a great OIS@AAO. It was our largest event by far. I don’t know if we’ll hit those numbers at OIS@ASCRS, but it’s promising to be a very exciting and dynamic event. So go to OIS.net, register to attend the conference on May 5, and we will see you in New Orleans.