Welcome to Glaukos Corporation's 4th Quarter and Full Year 2020 Financial Results Conference Call. A copy of the company's press release issued after the market close today is available at www.glacclus.com. At this time, all participants are in a listen only mode. After the speaker presentation, there will be a question and answer session. This call is being recorded and archived replay will be available online in the Investor Relations section at www.blackluz.com.
I will now turn the call over Chris Lewis, Director of Investor Relations and Corporate Strategy and Development.
Thank you and good afternoon. Joining me today are Glaukos' President and CEO, Tom Burns CFO, Joe Gilliam and COO, Chris Calcaterra. Following our prepared remarks, we'll open the call to questions. Since you're ample time and opportunity to address everyone's questions, we request that you limit yourself to one question and one follow-up. If you still have additional questions, you may get back into the queue.
Please note that all statements other than statements of historical facts made on
this call that address activities, events or developments we expect, believe or anticipate will or may occur in the future are forward looking statements. These include statements about our plans, objectives, strategies and prospects regarding, among other things, our sales, our products, our pipeline technologies, our U. S. And international commercialization, integration and market development efforts, the efficacy of our current and future products, our competitive market position, financial condition and results of operations, as well as the expected impact of the COVID-nineteen pandemic on our business and operations. These statements are based on current expectations about future events affecting us and are subject to risks, uncertainties and factors relating to our operations and business environment, all of which are difficult to predict and many of which are beyond our control.
Therefore, it may cause our actual results to differ materially from those expressed or implied by forward looking statements. Review today's press release and our recent SEC filings for more information about these risk factors. You'll find these documents in the Investors section of our website at www.glaukos.com. Finally, please note that during today's call, we will also discuss certain non GAAP financial measures, including results on an adjusted basis. We believe these financial measures can facilitate a more complete analysis and greater transparency into GovCoast's ongoing results of operations, particularly when comparing underlying results from period to period.
Please refer to these tables in our earnings press release that is available in the Investors section of our website for a reconciliation of these measures to their most directly comparable GAAP financial measure. With that, I will turn the call over to Glaukos' President and CEO, Tom Burns.
Thank you, Chris. Good afternoon, everyone, and thank you for joining us today. Before we discuss our 4th quarter results, want to spend a few minutes reflecting on the year 2020. By all accounts, the COVID-nineteen global pandemic created an unprecedented past year and challenged the conventional ways our companies, employees and customers operate both personally and professionally. The response plans we prioritized and implemented in 2020, including protecting the health and safety of our employees and their families, supporting our customers, preserving jobs globally, protecting core research and development projects and maintaining our strong and operating position following the pandemic have allowed us to stay focused and advanced our key strategic priorities during uncertain times.
As a result, I believe we exited 2020 more efficient and more capable company with fundamental prospects that have never been stronger. As a corporate pioneer of MIGS and corneal cross linking, we've been honored to partner with our customers and clinical investigators to help them navigate the rapidly changing environment through the implementation and expansion of various virtual and digital programs, including customer support, training, case proctoring and educational initiatives. I'm confident that these efforts have helped deepen our customer relationships and prepare us for the future well beyond COVID-nineteen. Finally, I want to thank these very customers for everything they are doing to serve the needs of patients worldwide during the pandemic. Overall, I'm proud of our performance this past year and of our team's resiliency and steadfast dedication to advancing our mission to create novel platforms that disrupt conventional treatment paradigms, advance the existing standard of care and enrich the lives and treatment alternatives for patients worldwide.
In doing so, we strive to create a world class global vision care leader uniquely positioned to drive innovation across glaucoma, corneal health and retinal disease. Within each of these areas, we are moving full speed ahead with the same pioneering discipline, pipeline development expertise and skilled commercial execution that has made us the worldwide leader of the MIGS marketplace today. Our ability to execute our plans over the past year not only illustrates our effective ongoing response to the current market environment, but is also a reflection of the progress we continue to make towards our broader strategic vision. Consider our key 2020 accomplishments. 1, we executed on our Corneal Health franchise integration, expansion and market development plans, evidenced by record new starts and for Trexis sales.
2, we successfully launched the next generation iStent inject W device in the U. S. And select international markets. 3, we reported strong international glaucoma sales and secured new market expanding regulatory approvals in key markets such as Australia, Japan and India. 4, we advanced key market access and reimbursement initiatives including the creation of new Category 3 CPT codes for high dose and standalone mix.
5, we implemented a global systems upgrade transformation designed to support long term growth. 6th, we executed financially during unprecedented times, not only through encouraging sales recovery trends, but also with strong gross margins, disciplined operating spending and continued preservation of our strong balance sheet bolstered by a $288,000,000 convertible debt financing to further strengthen our ability to aggressively invest in our pipeline and future growth opportunities. And last but certainly not least, we advanced our industry leading proprietary pipeline that we believe has the ability to significantly expand our addressable market opportunities beginning this year. As most of you know, our goal is to leverage our development expertise in commercial infrastructure to provide a portfolio of novel solutions that meet the full algorithm of customer needs. A key pillar in delivering on this strategy is the continued progression of our deep pipeline.
So I'd like to spend a few minutes highlighting exciting new clinical data shared earlier this year for 2 of our key glaucoma pipeline programs, iDose TR and iStane Infinite. Starting on iDose TR, our travoprost drug delivery implant, we were delighted to announce what we believe is powerful and compelling data that further underscores the potential for this technology to safely provide multiple years of sustained glaucoma pharmaceutical therapy and 20 fourseven compliance to tackle the significant problem of patient non adherence to topical glaucoma medication regimens. The recently announced 24 month interim analysis of our ongoing 36 month Phase 2b trial showed compelling results with both iDose arms continuing to demonstrate robust IOP lowering over 24 months to the magnitude of approximately 7 millimeters to 8 millimeters of mercury or nearly 30% reductions from baseline over the 1st 24 months. Interestingly, a subset analysis showed at least 20% of iDose subjects achieved robust average IOP reductions from baseline of at least 40%. Importantly, these results were achieved with a single iDose implant compared to the TYMLOS control arm that received twice daily drops over the 24 month evaluation period or nearly 1500 eye drops per eye.
As a reminder, iDose TR is implanted into the trabecular meshwork to avoid migration through a very facile procedure and the most recent Phase 2 data readout demonstrated a favorable safety profile with no clinically significant corneal endothelial cell loss, no serious corneal adverse events and no adverse events of conjunctival hyperemia reported to date in either high dose solution arm. We believe there is an important unmet clinical need and strong appetite within the ophthalmic community for safe, effective and durable sustained release pharmaceutical alternatives to traditional topical medications. And this powerful 24 month interim data reaffirms our excitement about the potential commercial prospects of iDose. We continue to progress towards enrollment completion in our ongoing iDose Tiara Phase 3 clinical program, which will mark another critical step in bringing this technology to the market. The 12 month Phase 3 trial results are expected to support our anticipated NDA submission for iDose TR in 2022 and we are targeting FDA approval for this promising technology in 2023.
The powerful iDose data available thus far underscores our confidence in the potential of this novel drug delivery platform to produce future generations of sustained therapies for glaucoma and potentially other ocular diseases. As such, we continue to invest resources to expand our pharmaceutical development capabilities and to develop future iDEST solutions. With that in mind, we are in late stage development with finalized designs for next generation iDose TR extended release implant, also known as iDose T Rex, which is in a similar size and form factor to the original iDose TR, designed to provide nearly twice the drug capacity to extend efficacy durations even longer. We will be engaging with the FDA in the near future to determine the most appropriate and expeditious regulatory pathway for this novel product. We are also seeking additional drug classes that may be synergistically used in conjunction with the iDose platform.
Through our research and development agreement with eWestern, we are currently assessing multiple ROCK compounds, which are showing positive results in animal models and we're establishing prototype implants for lead candidates in these same models. ROCK inhibitors when used in conjunction with prostaglandins have been shown as a powerful treatment in reducing intraocular pressure in U. S. Pivotal studies. Moving on to iStent infinite, our 3 stent system designed for use in a standalone procedure for late stage glaucoma patients, we are excited to have recently announced strong 12 month IDE pivotal data that shows 76 percent of subjects achieved 20% or greater reduction in month 12 mean IOP on the same or lower medication burden with more than 50% of subjects achieving month 12 IOP reductions of at least 30%.
Subjects also achieved a 13% mean reduction in medication burden at 12 months and the safety profile in the study was highly favorable with no explants, infections or device related interventions or hypontinib reported through 12 months. When pairing these strong pivotal results with the advanced disease progression profile of the enrolled subjects that were on an average of 3 medications with 2 failed prior surgeries, we believe ophthalmic surgeons will view iStent Infinite's risk benefit profile very favorably and as a compelling new treatment option. We continue to target FDA approval of iStent Infinite in late 2021. Beyond these important glaucoma pipeline programs, we also remain in early preparations for the potential U. S.
Commercial launch of Santen Pharmaceuticals Pressorflow MicroShunt, an elegant AbEx terminal surgical implant for late stage glaucoma management. We continue to ramp up our commercial preparations for this promising opportunity ahead of an anticipated FDA approval and commercial launch. We also recently announced that we are in late stage development of Eye Prime, a highly complementary new visco delivery device designed to be a truly minimally invasive system to further support the needs of physicians and patients. Within Cornell Health, we issued a separate press release this afternoon announcing positive Phase 3 results for our next generation corneal cross linking EyeLink Epione investigational therapy. We're excited to announce results from the multicenter, randomized, placebo controlled Phase 3 pivotal study that met the primary efficacy endpoint with statistically significant improvement in maximum cornhole curvature or K MAXX.
K MAX is an objective measurement of the steepest corneal curvature based on corneal topography where an increase in K MAX denotes corneal steepening and keratoconus disease progression. At 6 months, the FE arm treatment arm showed a K MAX mean improvement of 0.2 diopters from baseline compared to a K MAX mean worsening of 0.8 diopters from baseline in the placebo control arm, resulting in the statistically significant mean treatment effect of 1 diopter meeting the study's primary efficacy endpoint. Most importantly was that the Epione therapy demonstrated the ability to halt or reduce the progression of keratoconus while disease progression was observed in this study's placebo control arm. The treatment was generally well tolerated and the majority of adverse events reported were mild and transient in nature. These positive results underscore our view that Epione may provide the ophthalmic community in keratoconus patients with the 1st non invasive bio activated drug treatment alternative designed to reduce procedure times, improve patient comfort and shorten recovery times.
The positive Phase 3 results are expected to support a U. S. NDA submission in 2022 and we are targeting FDA approval for Epione in 2023. Beyond these near to medium term opportunities, we also continue to invest in and advance our key earlier stage R and D programs, including in dry eye and retina. While these opportunities remain in preclinical developmental stages, we are excited with the initial progress we're demonstrating within these programs.
Our pipeline has the ability to fundamentally transform Glaukos by significantly expanding our addressable markets over time. To enable this, we have built a strong balance sheet to provide us with the financial flexibility to remain on offense as the COVID related dynamics play out by expanding our global infrastructure, strengthening our pharmaceutical expertise, upgrading our enterprise systems, advancing our core R and D programs and supporting our clinical programs as they progress towards becoming commercial realities. And speaking of commercial realities, we've been pleased with strong recovery trends in our business since the peak of the pandemic that continued through the Q4. While procedure recovery trends remain somewhat volatile, I've been encouraged by how physician offices, ASCs and hospitals are navigating this new normal. And I'm pleased to report 4th quarter net sales of $73,200,000 that exceeded our expectations across our glaucoma and corneal health franchise globally.
During the Q4, we commenced an official full scale launch of the iStent inject W in the U. S. The iStent inject W built upon the proven foundation of our inject platform and is designed to offer ophthalmic surgeons the same established safety and efficacy of iStent inject with the added benefits designed to optimize stent visualization, streamline implantation and deliver procedural predictability. Early field feedback and real world results for iStent inject W remain very positive and reaffirms our confidence in the commercial prospects for this important technology. We've also launched iStent inject W more broadly in many of our key international markets, including various European countries, Japan and Australia.
This adds to a number of 2020 accomplishments in our international glaucoma franchise that positions us well for long term growth, including standalone indication approval in Australia, iStent inject W regulatory approval in Japan, iStent and iStent inject regulatory approval in India and continued progress across many of our key market access initiatives. Finally, over the course of 2020, we made significant strides to firmly establish Konia Health as a new franchise and future growth engine for our organization. Not only are we ahead of plan on the cost savings targets we announced at the time of the deal, but more importantly, we continue to execute on our commercial strategies and market development initiatives, which include driving increased awareness of keratoconus broadly across the optometric and ophthalmic community, advancing the diagnosis of this important debilitating condition, streamlining the referral pattern from initial diagnosis to treatment, implementing customer friendly programs to drive new account starts, optimizing reimbursement, investing in health economics to further solidify the value of corneal cross linking to patients and healthcare systems, and finally, training corneal health professionals on our ILLETE procedure. To support this progress, we continue to opportunistically expand our U. S.
Corneal health commercial team. We are pleased to see another new record for U. S. Vitrexis sales established in the Q4, an encouraging sign on our strategies and programs we've introduced are resonating. While we remain in the early stages of unlocking the combined organization's full potential, we're encouraged with this performance and excited about the opportunity ahead.
So in summary, we're creating the unique vision care leader prepared to drive a robust cadence of innovation that can significantly expand our market opportunities and drive sustainable growth and profitability over the next decade. While we of course remain cautious on the near term uncertainties associated with the COVID-nineteen, the strong foundation and team we've built leaves me confident in our ability to execute on our plan and advance our mission to transform the treatment of chronic eye diseases for the benefit of patients worldwide. So with that, I'm going to turn the call over to Joe to discuss our Q4 2020 financial results. Joe?
Thanks, Tom. As a reminder, I will be discussing our financial performance on a non GAAP or pro form a basis and will summarize our GAAP performance later in my prepared remarks. I encourage each of you to review our GAAP to non GAAP reconciliation, which can be found in today's press release as well as the Investor Relations section of our website. Glaukos net sales for the Q4 of 2020 were $73,200,000 representing sequential growth of 13%. Net sales grew 11% versus Q4 2019 reported sales of $65,800,000 and increased approximately 1% on a pro form a year over year basis adjusting for a full Q4 2019 contribution of Avidro given that transaction closed in November 2019.
These results exceeded our expectations and reflect the continued recovery despite ongoing COVID-nineteen related headwinds and associated volatility. With respect to the pandemic impact, it is worth noting that performance in the quarter was strong across each of our franchises, but we did experience more intra quarter volatility than normal, including a more pronounced softness around the holidays in November and exiting the year than we might typically experience. Now turning to our U. S. Glaucoma franchise specifically.
Our 4th quarter U. S. Glaucoma sales were approximately $43,700,000 representing sequential growth of 12%, which we believe reflects a combination of COVID related dynamics, a more stable competitive landscape and continued stable pricing. It is also worth noting that we began to see an uptick in new doctor training during the quarter, an encouraging sign even if we are not fully back to normal yet. Internationally, our glaucoma franchise delivered 4th quarter sales of approximately $14,600,000 representing sequential growth of 15%.
The COVID-nineteen impact for international glaucoma business has varied by market, but our overall recovery in the quarter was led by Japan, Australia and the other major European markets, while the situation in Brazil and Latin America generally remains challenging. In Corial Health, 4th quarter net sales were $14,900,000 representing sequential growth of 15%. The 4th quarter performance was driven by record U. S. Botrexa sales of $12,500,000 and the continued trend of strong new U.
S. Botrexa starts as our commercial integration and strategies continue to deliver despite the pandemic. Shifting gears for the remainder of our P and L, our non GAAP gross margin in the 4th quarter was approximately 83.4% versus 84.7% in the same quarter in 2019 84.9% in the Q3 of 2020. This reflects the modest headwinds associated with iStent inject to iStent inject W transition and the sale of inventory that had been produced less efficiently during the height of the pandemic. It is worth noting that our non GAAP adjustments to COGS include substantial adjustments related to Avidro acquisition accounting.
Our overall non GAAP operating expenses were approximately $61,500,000 in the Q4 of 2020, remaining below pre COVID levels, but up 7% sequentially compared to the 3rd quarter as we continue to reverse temporary cost saving initiatives and restore expansionary spending as the recovery warranted, a trend that we would expect to continue in 2021. Our non GAAP SG and A expenses in the 4th quarter were approximately $40,200,000 up 7% sequentially compared to the 3rd quarter, reflecting increased commercial activity. And our non GAAP R and D expenses in the 4th quarter were approximately $21,300,000 up 6% sequentially compared to the 3rd quarter, as we continue to restore earlier stage pipeline programs and human capital investments across the organization. We finished the 4th quarter with a non GAAP operating loss $400,000 and a non GAAP net loss of $800,000 or 0 point 0 $2 per diluted share. Our GAAP net loss was $10,600,000 or $0.24 per diluted share for the Q4 of 2020.
We invested in approximately $2,100,000 of capital expenditures in the 4th quarter. Now looking ahead, we expect our capital expenditures to increase substantially over the next 2 to 3 quarters as we enhance and expand our facilities in Southern California and Boston to meet our expanding development and operational needs. As of December 31, 2020, we had cash, cash equivalents, short term investments and restricted cash of approximately $414,000,000 an increase of $16,000,000 compared to $398,000,000 at the end of the Q3 2020. Finally, let me make a few comments on the state of our markets and opportunity today and how we believe things are unfolding for 2021. We believe the competitive landscape and pricing dynamics remain stable across each of our major business areas.
And as Tom mentioned earlier, our integration efforts and strategies are driving increasing penetration in corneal health alongside a successful launch of Vicent inject W globally in glaucoma. Not surprisingly, the overall ophthalmic market still face COVID related headwinds in terms of new patient consultation visits, practice closures due to personnel testing positive and the ability of surgical practices to work fully staffed and at full capacity given enhanced safety protocols. Having said that, we've been encouraged by improving trends on each of these fronts through the Q4 and thus far in 2021. We've also been encouraged by our improving new surgeon training trends and our increasing access to practices, albeit with restrictions that make typical day to day commercial activities challenging still. We do recognize though that the dynamics associated with COVID-nineteen and its variants remain fluid.
For example, as the global vaccination efforts ramped in late January February, it appears that some patients may be predictably electing to defer procedures until after they've been fully vaccinated. This is a short term but relevant trend. To put this in context, our performance thus far in 2021 has exceeded our plan as we experienced year over year growth trends across each of our franchises in January. But the vaccine dynamics and several off selling days throughout much of the U. S.
Due to the recent severe winter weather led to a softening of those trends in February. As we put all this together in the context of our expectations going forward, we expect Q1 2021 net sales to increase approximately 15% to 20% compared to Q1 2020, which reflects our typical seasonality patterns and the Q1 trends I disclosed earlier. It is worth noting that we believe the range of potential outcomes for the full year 2021 remain more sensitive to COVID-nineteen and the dynamics associated with the rollout globally of vaccines than the increasingly solid underlying fundamentals for which we have a degree of control. Having said that, assuming the pandemic related trends continue to gradually improve from here, we would expect our 2nd quarter sales to increase sequentially versus the first. And with that, I'll now turn things back to Tom for a few closing remarks.
All right. Thank you, Joe. I would like to conclude by acknowledging how proud I am of the actions our organization has taken throughout the COVID-nineteen pandemic, while advancing our key strategic priorities in a rapidly changing environment. We are focused on near term execution and excited about our long term future, where in just the next 3 years, we expect to have 5 major new product introductions. Beyond that, we have a fulsome portfolio of pipeline opportunities as we seek to build and expand upon our core microsurgical and sustained release pharmaceutical platforms.
While the ongoing pandemic may well persist through 2021, the strong foundation and team we have built leaves me confident in our ability to execute on our plan as we strive to create a strategic vision care leader with disruptive franchises across glaucoma, cornea health and retinal disease. And with that, I'll open the call to questions. Operator?
Your first question comes from the line of Andrew Brackmann from William Blair.
Hey, guys. Good afternoon. Thanks for taking the questions. Tom, maybe start on your iDose commentary from earlier in this year. When you released that 24 month data, you showed obviously this was in a sort of trial, which was kind of in a vacuum because it ensured compliance.
So maybe two questions here. First, how are you thinking about those results in sort of a more apples to apples or real world comparison? And then secondly, as we think about future reimbursement efforts here and commercialization efforts, how well do you think that dynamic is understood by payers and then ultimately users under this product?
Well, thanks, Andrew. Happy to answer your question. Well, first of all, I think when you look at the data, I think the people have been following my comments in this area for many years. We initially said that we needed to have a product that provided consistent IOP reductions in pressure for at least 6 months to have a commercially viable program or product. If we reached 12 months, we thought we had the ideal.
What I'm so excited about when I look at this data is that we're now looking out at 2 years with average mean IOP reductions of 7 millimeters to 8 millimeters, nearly 30% reductions in pressure from pretreatment baselines. So this is pretty extraordinary. And this is an intracameral implant that is done with a facile procedure. It's not subject to migratory change like you'll see with erodible implants. It has a superlative safety profile.
We saw minimal endothelial corneal cell loss with the I dose versus placebo. And we didn't see conjunctival hyperemia or hyperchromia. So the data is superlative. We're going to continue to track the data out for 3 years and see if we can get some additional hang time by following these patients out. So I am extraordinarily pleased with the data we've been able to present.
And I think that gives us powerful prospects when we do seek reimbursement going forward when we commercialize. We clearly already have a Category 3 CPT code established for the professional fee payment side well in advance of commercial approval. And then we'll seek and generate a J code, which will allow us then to carve out and receive a fair value proposition for the iDose when we commercialize. We're doing all of the extensive pharmacoeconomic work that you would expect behind the scenes. But importantly, as investors, when you look, for instance, at Derista, a rollable implant that lasts typically in the range of 4 to 6 months, we're seeing that the J code established for that product is around $2,000 So I'm not going to suggest any proportionality based on sustained release delivery, but I will tell you that that's an excellent precedent and predicate for us as we establish the basis for our J code when we do commercialize.
So I can't tell you how excited we are about the data, the appetite and the pulse that exist, the resonating feedback we're receiving from surgeons since we've introduced this data. And I think it becomes a powerful platform for us to enter the next stage of our development and growth.
Great. Thanks for that, Tom. And then, Joe, maybe one for you, a little bit more granularity on the trends that you're seeing here so far 2021. Anything specific that you point to in terms of prevalence of COVID or reopening in certain states that gives you more or less confidence here as it relates to how you think the U. S.
Market looks sort of on the other side of post vaccination or more uniform declines in cases? Thanks for taking the questions.
Yes. Thanks, Andrew. Yes, as I could be trying to say in the prepared remarks, obviously, the U. S. Dynamics remain fluid.
I think 1st and foremost, as it relates to the COVID trends themselves, we see the same data obviously that all of you are seeing as it plays out here in terms of improving underlying trends of the disease transmission. And so we saw that really through the Q4 and thus far into the first. What we're seeing now is a little bit of, I think, transitory or transient impact from the vaccine rollout. It's probably to be expected that as patients are in the category that can get vaccinated, they tend to hold off a bit more on their procedures until after they've been fully vaccinated. And so that's what we're trying to talk about in the context of a really strong January for us that softened a little bit in February as the vaccine rollout started to happen.
As we think about that beyond and obviously a comment on this, we would expect sequential improvement from here, all else being equal with respect to COVID, its variance and the global rollout of those vaccines. But I think as we look forward and we've tried to resist making too many predictions about the way COVID will play out over many periods of time. But sitting here, we're increasingly encouraged with the trend line that is emerging for the year.
Great. Thanks, guys.
Your next question is from the line of Matt O'Brien with Piper Jaffray Sandler.
Hi, guys. Good afternoon. This is Drew on for Matt. Thank you for taking the questions. I appreciate the color on the first couple of quarters here.
I know you don't want to provide guidance for the 1st year or for the full year, but maybe you could help us a little bit directionally as we think about 'twenty one. I guess in 2019, your glaucoma business is about a $230,000,000 business. Is there any reason to think that 2021 can't post a little bit of growth off that 2019 figure?
Thanks, Drew. Well, obviously, we're not giving that full year guidance directly or indirectly. And I think it has a lot more to do with the piece and how the vaccine rollout happens globally. That some of the dynamics that we're seeing in the U. S, how they do or don't emerge in the ex U.
S. Markets, especially as vaccines pick up there as well and the timing of all that. But what I'll say is kind of what I said in the first question here. I think we're increasingly encouraged by the trend lines that are underlying what's happening. And if the world, including the United States continues to progress the way we're seeing it, both in terms of COVID-nineteen and the vaccines, I think we're set up for hopefully incremental growth as we progress throughout the quarters of 2021.
Understood. And then obviously, I just want to touch on the FPI data. Congrats, it looks like very good data. I just wanted to drill down a little bit more into it. And I apologize, I'm going off memory a little bit here.
So correct me if I'm wrong. But I believe in your EpiOff, FDA studies, you're getting a little bit closer to that 2 diopter mark between loads of treatment in the sham at 6 months and then a little bit of improvement out to a year. Obviously, at the on comes with a much improved safety profile. But I guess, one, is that an appropriate comparison and how clinically significant is that delta? And then 2, what role do you see for the combination of these therapies once you have both available?
Thank you.
Great questions. This is Tom. As we look at the data, it's hard to draw comparisons between the data that we see that we just disclosed versus the earlier data with EPI off because even though the patients have similar inclusion criteria, Clearly in the EPI ON study, we had patients where we recruited more earlier intervention patients who are slower progressors. So it's hard to do an apples to apples comparison. I will tell you that we're excited about the data, the fact that we can perfuse oxygen on the surface of the eye, use a surfactant to be able to drill through the corneal epithelium and use a higher UVA radiation protocol, we are able to achieve this one doctor difference versus placebo and be able to shut off progression and halt progression in the patients.
What I do think is I do think by removing the corneal epithelium, you will see a greater reduction in K MAX. And so to answer your question, I see an excellent opportunity to bifurcate and segment the market and to use Epione in earlier stage, earlier intervention, perhaps in patients on a little more modest to moderate disease progression, we'd be able to reserve Epi OFF for patients who were in more advanced stages who need to have a not only a halt with progression, but need to have a nice reduction in K MAX moving forward. So to me, it offers us a great opportunity to bifurcate segment and be able to serve the market algorithmically much like we do on the glaucoma side where we have different technologies for different disease stage management.
Thank you. You're welcome.
Next question is from the line of Robbie Marcus with JPMorgan.
Hi. This is actually Alan on for Robbie. So I had a quick question on kind of the market dynamics that you saw entering the year. You highlighted that competitive trends have stabilized, but just kind of diving a little bit deeper into that. When we look back to the last we saw of normalized trends, it did look like there was a little bit of going on even though you said the market was still growing healthy double digits.
So when you say that stabilized, how should we really think about that with respect to that double digit growth number and also whether or not you're still seeing any amount of competitive erosion from like both similar MIGS devices and also more invasive surgical alternatives?
Thanks, Alex. It's Joe. Maybe I'll start and Chris, if you want to add some color, if you can. I think the way to think about the competitive landscape, obviously, there's an awful lot of other things going on in the marketplace from COVID. So I probably will resist from commenting on the specific percentages and numbers that you were referencing.
But I'll say this, obviously, if you go back a year, as we're entering into 2020, we talked on this very call about some of the emerging competitive landscape dynamics and what we thought that would mean for the business as it unfolded in 2020. Obviously, a lot happened over the course of 2020. We feel good about the way we've navigated that. We feel good about our product introduction in the form of IcinJectW and generally our access to accounts and the relationships that we have there and what that's meant for our business. So what we're saying is, is I think if you look back versus a year ago and how things have transpired, we feel like that competitive landscape noise, if you will, has settled a bit and is much more stable relative to sitting here 12 months ago.
I have a little color as well, Alan. This is Chris. I would say going back a year ago, there was a lot of trying and trialing going on. And since then, there's less of that. Speaking of Ivantis, it's been out there.
The Hidus has been out there for 2 years. And we've had a very good recapture rate of those accounts that have been trying that product. Additionally, in July of last year, you had the NCCI edit on the omni device. That too has had an impact. And then finally, as Joe mentioned, the iStent inject W has done very well for us and has been well received by the ophthalmic community.
And I think all of those factors have led us to say that the competition, competitive environment is stable to improving.
Got you. And then just
a quick follow-up. You're slated to still launch your kind of first forays into the more moderate to serial environment with MicroShunt and Infinite. That's it's a market where there's already competitive devices out there already. So how should we think about your ability to really drive uptake with those products and whether we should expect any kind of revenue benefit in 2021 or if that's more of a 2022 story? Thank you, guys.
Sure. I'm going to talk about the product itself in the first part of your question, Joe will follow-up with the financials and so forth. As we talk to key opinion leaders and do our channel checks on this product with those who have been in the investigational stage. And by the way, it's also in Europe at this stage, it's a less invasive procedure. The material itself is more biocompatible.
And there really hasn't been a lot of new products in end stage therapy glaucoma. And we're excited about this product because it serves as a capstone to our overall product portfolio in our algorithm. And there's a place for this product. And we think that while the market is not as big as the combo cataract market, it's still significant. And this product has the potential to really have an impact on the marketplace and we're excited to have it and we see it as an important product within our portfolio.
Yes. And in terms of the numbers, Alan, I think, obviously based upon the commentary from our partner Santen, we continue to expect that we should be able to see MicroShunt in 2021. And as a result, we would hope that that has some contribution this year. We're certainly preparing organizationally for a commercial launch around that product as soon as they're able to hopefully gain an approval. But whether it comes to that product or iCine Infine or any others, clearly there'll be a more pronounced impact to 2022 as we turn the corner there and get hopefully full year benefit of sales for both iCE and Infinite as well as MicroShunt.
And your next question is from the line of Chris Cooley with Stephens.
Good afternoon. Thanks for taking the questions and hope everyone is well. Maybe just 2 for me. If we could start with record sales of POTREXZA. Could you give us some additional color there, whether you're seeing that as a result of an expanded installed base.
I know there were some metrics that you provided at the time of the Avedro acquisition announcement. Just kind of curious how you track relative to that Or if you're just seeing greater utilization within some select practices now that better understand the therapy and have good protocols for employing those patients through the channel. And I've got a quick follow-up.
Hey, Chris. It's Chris, and I'll address your question. I would say it's a combination of several factors. I think the fact that we've expanded the sales organization both by adding Corneal Health sales managers as well as integrating our existing glaucoma sales reps into the process. I would say it's a stabilization of reimbursement.
Our market access team, which is clearly the best in the industry, has done a fantastic job of stabilizing reimbursement. I think it has a lot to do with our marketing programs where we've reached out to the optometric community to identify early diagnosis and then referral patterns into those practices who do the EyeLink procedure. I think it's also the flexibility that we've had around the capital equipment placement by providing different programs to ensure that the equipment was an impediment to the sale. And a lot of direct to consumer campaigns and digital campaigns and webinars, all of these things have combined to increase placements as well as utilization within existing accounts.
Yes, I'll just add one quick thing to that Chris, which is numerically 2020 when you look at despite the pandemic, as you've heard us say, I think on multiple cases over the course of the year, we had record new starts or installations of systems in the U. S. So the numbers back up what Chris is talking about in terms of expanding access to Votrexa and then within those accounts driving incremental utilization through all the referral networks and the things that Chris is talking about. I really think it's been a combination of both when you think about building your models.
I appreciate all the color there. And then just lastly from me, I'll throw out a trouble work here, see if we can get anything. But on the Q4, obviously, the operating expenses there were below pre COVID levels. And while you gave us top line guidance for the Q1, just would appreciate any color you could provide about how we should think about the operating expenses in aggregate as we start to flow back through the year, obviously assuming there's going to be some more travel, higher sales, so hopefully so with that greater commission. But just trying to think about that coupled with the investments you're doing, any kind of commentary you could provide around expenses on the operating line would be appreciated.
Thanks so much.
Sure, Chris. Happy to do that. I think what you've seen now is a little bit of the pattern of how we're trying to manage our spending relative to the recovery, right? You've seen sort of the low water market where we could get the business to in Q2 and then how that sort of recovery has managed it from a spending standpoint relative to the sales recovery in Q3 and now Q4. What I can say is that we're going to remain extremely disciplined around how we think about spending within the organization.
But as you saw in the Q4 and as I would expect to continue the course of 2021, we are continuing to move forward in 2021.
Next question from the line of John
2Q growth sequentially over the Q1 assuming that the favorable COVID trends 2018, 2Q was up around
any color
you can give there? Thanks.
Hi, Trevor. Yes, that's a great question. I don't know that we're prepared to get quite that granular on it. What I would tell you is the numbers on what we're saying for the Q1 is, we've kind of gotten back to a place where we're
established a little bit of growth on
a pro form a basis
If you include
we're seeing a little
bit of growth, and we
hope to continue to expand that growth quarter on quarter as we move forward here.
Okay, great. And then just another one on the guidance or just from 2020 that is, so you initially guided to $190,000,000 did $140,000,000 in U. S. Glaucoma business. So if you do the full bit of math there, it's about $50,000,000 $55,000,000 that was arguably deferred as a result of what happened.
Do we think about that as being like a 2021 phenomenon in terms of the recapture? Any sort of commentary you can give there would be great?
Yes, sure. I think that the recapture dynamics are going to be fairly elongated the way it will play out. I think that's going to be driven more by the ability of the accounts themselves to execute on procedural volumes. There's only so many hours in the day and so many days in the week that they can be doing procedures and bringing in these patients. So I think what we're likely to see is a more prolonged market tailwind when we get on the other side of the majority of the vaccinations as well as hopefully a lessening in the COVID cases themselves.
Great. Thank you.
Next question comes from the line of Ravi Moshari with Berenberg Capital Markets.
Hi. How are you doing? Thanks for taking the question. So I just want to kind of if I can ask about the
sorry, I just kind of lost my train of thought.
If I can ask about the yes, the timing of maybe iStent in India and the market analysis that you have over there, can you help us maybe size that opportunity and some of the penetration dynamics that you're thinking about in terms of timing of how you plan on kind of getting into that arena? And then I have a follow-up. Thanks.
Sure. Hey, Robbie, this is Chris. We're very pleased that we were able to secure FDA or excuse me, approval in India for both the iStent and iStent inject, okay? So we'll have both products. We're currently working through commercialization plans.
It is our hope that we would initiate that sometime here in the near future. But beyond that, we're not in a position to be able to give more details. Obviously, given the size of the market in India, we're very excited about it and we do understand the economic and reimbursement dynamics there and we are bullish on what we can possibly do. So more to come.
Great, thanks. Then maybe one on Epione. You're talking about segmenting the market. If I remember right, when you kind of first talked about the rationale behind the VITREXZA and kind of VEDRA deal, market development was something that really needed to be done to generate awareness of the condition. And I'm curious, kind of given the timing expectations around the kind of approval and commercialization that you're shooting for now on this, is this something that you're going to be kind of building in advance?
Or is it something kind of from an investment perspective you're going to be holding off on to drive that?
So Robbie, this is Chris again. I would say that it dovetails. We're doing all those things now with EpiOff, really have made a big investment in terms of getting out outreach with optometry and working with them to diagnose this disease earlier, working with reimbursement to ensure stable reimbursement, all the things that I mentioned in an earlier question. I think when ePI on comes, then there'll be the added benefit of this product being less invasive than the EPI OFF procedure and we'll continue to invest. But at that time, there'll be more awareness of keratoconus and the treatment and the FDA approvals of EpiOff and then EpiOn.
And we will be focusing more on the product itself and the fact that this should appeal to more patients and more surgeons given the less invasive nature of that procedure.
Great, thanks. Maybe if I could sneak in one last one. Just on the ROCK inhibitors commentary and the kind of prostaglandin, it sounds like you're saying it's an animal model with some of the testing right now. Should we think about that kind of from a kind of 3 year window, 5 year window, 7 year, like how to help us kind of frame when something like this could potentially come to market? Thank you.
Hey, Robbie, this is Tom. And what I would tell you is that the development process is probably multi year. So I'll keep it higher level. The reason we're excited though is when we look at the additive value of ROCK inhibitors when used in combination with prostaglandins, we see some really significant differences in ability to be able to reach target levels in IOP reduction that hadn't been reached with other combination products. So it's one of the reasons I'm bullish on being able to hunt and define the right ROCK inhibitor that we can put into the iDose vessel that will be a complementary combinatorial treatment with iDose in the future.
I believe strongly that if we get this right that we'll see the use of iDose TR in combination with iROC in a number of patients with either moderate to progressive open angle glaucoma. So it's an exciting area. We are operating within the parameters where we have to find a compound that has really high resilience in terms of stability and really potent a highly potent, low nanomolar concentration ROCK inhibitor. That's why we're picking through a number of primary candidates. We'll find the right one and we'll advance that.
It will be multi year, but when we have it, it will be I think an extraordinary addition to the glaucoma portfolio.
Next question from the line of Anthony Petrone with Jefferies.
Hi, good afternoon. Hope everyone is doing well. I have 2 quick ones in there based on channel checks we've done. First on iStent W, our understanding is that solution, the major feature there is surgeon ease of use. And so I'm wondering, A, how many iStent inject users have actually transitioned to W?
And do you believe W will be market expansive on the surgeon adoption end because of ease of use? And then the second is on reimbursement coding, our understanding is new coding for Omni is allowing Omni to be used with the MIGS stent implants and that can go down the severity curve. And so I'm just wondering how that's going to play out in the marketplace when you consider the additional reimbursement for surgeons? Thanks.
Anthony, this is Chris. Let me start with W. I think your channel checks are right. I think people do see the W as a big improvement over iStent inject. That is because of the flange being larger.
That's the component that is visible within the angle of the eye. And with that, that brings more predictability. What a lot of doctors maybe haven't told you in your channel checks is that we've also improved the insertion device itself and that is made for more predictability. So we feel like this has been a big investment and that the acceptance level of this product has been very high. And I do believe that this has helped us to share and is helping to expand the market with this product.
And to be clear, iStent inject W is replacing iStent inject. So right now in the U. S, the two choices are iStent and iStent inject W. Moving to your thoughts on Omni, that is a visco delivery system. There are doctors who are utilizing this product in combination with trabecular bypass.
This is a new trend. So it's complementary to what we have. Some people do it in standalone as well. But the concept there is that you expand the canal and then you place a trabecular bypass device in as well. So 2 separate codes, they're able to be used in harmony with each other.
We think that given all the advantages of Isted Inject W that it's the ideal trabecular bypass device to be utilized with this technology because of its predictability, its visibility, its efficacy and its superlative safety profile and perhaps even ease of use. So I think that addresses your question?
Yes, very much. Thank you very much.
I'll hop back in.
Anthony, I'll go ahead. This is Tom. I'll just add a few things. 1, I'd like to believe this is something we foresaw. So when we look at the NCCI edits, which precluded surgeons from using visco canelostomy codes in conjunction with boraniotomy, we presumed and thought that there'd be a natural pivot to using the visco canalsy device in conjunction with stents, in this case, the trabecular bypass stents.
So wasn't lost on us. And so I believe we've been pressured now. If you can see our development plan and product development plan, we now have I Prime under development. IPrime then you can fast forward and think about it in use in conjunction with iSpend inject or iSpend infinite to treat these patients. It gives us tremendous flexibility either using a visco canalsy device or visco dilation device as a standalone treatment or in combination with a plethora of products that we have.
It's expanding our algorithm and I think it's going to give us the ability to continue to generate robust growth within the glaucoma area in the future.
Very helpful. Thank you.
And your final question comes from the line of Steven Leichman with Oppenheimer and Company.
Thank you. Hi, guys. Just a couple for me. Heading into 2020, you targeted 500 plus physicians trained on MIGS. Obviously, COVID changed that.
Wondering where you wound up coming in last year and any goals you're willing to provide on physicians trained in 2021?
Hi, Steve, it's Joe. Yes, I think first with respect to the 2020 target, you're right, obviously, COVID took a chunk on that. I will say without getting too specific, we ultimately landed much closer to that number than I would have predicted back in March, April, May timeframe. It really speaks to the commercial organization, the creativity that they engaged virtually in bringing forward a lot of physicians who had maybe a little extra time on their hands and ultimately bringing it forward. So I think that we were encouraged by that.
As you heard in the prepared remarks, we're very encouraged by the Q4 in particular, hopefully the realization of the full year of work. And as we turn the corner in 2021, I think we're not giving a specific number. There's too many variables there in play with COVID and the like, but our guys continue to get increasing access and hopefully we can continue to drive that important market driver.
Great. Thanks. And then just secondly, also heading into 2020, you had guided to your $300,000,000 of OpEx spend, but you were able to keep that well under response to COVID. And then you mentioned that you're going to keep a close eye on OpEx spend given the variability in the marketplace. But is that still a place where we should a number we should be targeting on a run rate when things get normalized?
Is that or have you found some underlying cost savings that perhaps won't get you back up to $300,000,000 in the near future?
I think it's a fair question, Steve. The way I would think about that is $300,000,000 represented, obviously ex COVID where we saw that the business and our investments trending. That's based upon fundamentals both in terms of our commercial infrastructure expansion as well as our R and D pipeline. So I think that still remains a pretty good bogey in terms of where the spending can go. Where we get between our current run rate in there has more to do obviously with the pace of the recovery from a COVID standpoint as well as the normal things, right?
I mean, anytime you're trying to bring forward exciting new technologies from a especially from a development standpoint, the pace
in which some of those
things click and where they increase their spending as you move into the clinic and things like that can really drive how close you get to $300,000,000 in any given point in time. But clearly that's the direction that we're heading. And there's, as you know, been no significant change in our overall strategic plan and what we're trying to accomplish from an R and D standpoint.
Makes sense. Thanks, Joe.
And I would now like to turn the call back over to Chris Lewis for closing remarks.
Okay. This is actually Tom. I want to thank all of you for your time and attention today. We hope and trust that everyone is staying safe and we want to thank you for your continued interest in Glaukos Corporation. Goodbye.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.