Greetings, welcome to the Aurinia Pharmaceuticals Dry Eye Results Conference Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Miss Celia Economides, Vice President, Corporate and Public Affairs for Aurinia Pharmaceuticals. Thank you. You may begin.
Thank you, operator. Good morning, everyone, welcome to Aurinia's presentation of our Phase II Dry Eye Syndrome results. With me on the call today from Aurinia are Richard Glickman, Chairman and Chief Executive Officer, Dr. Neil Solomons, our Chief Medical Officer, and Michael Martin, our Chief Operating Officer. Joining us for the Q&A portion of this call will be Dr. Joseph Tauber, Principal Investigator and head of the renowned Tauber Eye Center in Kansas City, Missouri. Earlier today, we issued a press release announcing the results of our Phase II head-to-head study of voclosporin ophthalmic solution versus RESTASIS for the treatment of dry eye syndrome. The press release and financial statement package is available on our website at auriniapharma.com. A 6-K was filed with the SEC as well.
I'd like to remind you that today's presentation is being webcast live on Aurinia's investor relations website. A replay will also be available following today's call. The content of today's call is Aurinia's property. It cannot be reproduced or transcribed without our prior written consent. During the course of this call, we may make forward-looking statements based on current expectations. These forward-looking statements are subject to a number of significant risks and uncertainties. Our actual results may differ materially. For discussion of factors that could affect our future results and business, please refer to disclosure in today's press release, our most recent filings with Canadian securities authorities, and our reports that we file on Form 6-K with the U.S. Securities and Exchange Commission. All of our statements are made as of today, January 22nd, 2019, based on the information currently available to us.
Except as required by law, we assume no obligations to update any such statements. With that, let me turn the call over to Richard. Richard?
Thank you, Celia, and thank you all for being on the call this morning. Apologies to you folks living on the West Coast for this early hour. This morning, I am very excited to share the results of our exploratory phase II head-to-head study of VOS versus RESTASIS in the treatment of dry eye syndrome. I have a few comments to make, then I will turn the call over to Dr. Neil Solomons to provide a detailed review of the data. First, a quick thanks to the team for the hard work in conducting the study and to the patients and physicians who participated. Many of you recall that VOS is a product that we've had in our possession for quite some time, we thought that it would make some sense to spend a little money to see if we could generate some interesting data.
That's exactly what we've done here. Our exploratory study produced some very important results that will guide the future development of VOS. This study is one of the only head-to-head studies conducted between a development agent and the current market leader, RESTASIS, for the treatment of dry eye syndrome. One of our goals was to assess the potential differentiation of VOS and whether it could be a strong clinical and commercial contender in the dry eye market. We designed our trial to look at a number of endpoints, including the primary, which was a simple component to ocular tolerability called drop discomfort. It's a subjective endpoint that is measured after a patient receives one drop of the drug and scores his or her discomfort on a Visual Analog Scale at minute one of the study.
We also evaluated a number of challenging objective endpoints that have previously formed the basis of approval of the three currently FDA-approved dry eye therapies. Our working hypothesis was that 100 patients would be enough to see a difference in drug installation discomfort at one minute, it was unlikely that we would see statistical significance of the other, more relevant and challenging efficacy endpoints, given the sample size and short duration of the study. Clearly, we were wrong. In our study, both VOS and RESTASIS generated surprisingly low discomfort scores, both were very well tolerated. Definitely not the right choice as our primary endpoint in this exploratory study. However, we never imagined that the more challenging objective and subjective endpoints that encompass both signs and symptoms would yield such statistically significant and clinically relevant results.
These results, which Neil will be presenting shortly, have given me tremendous confidence that Aurinia should aggressively pursue the clinical development of VOS, should these efficacy data be supported, VOS has the potential to make a major contribution to the treatment of dry eye syndrome. I will speak more on this after Neil presents the detailed results. With that, I'll turn the call over to Neil, who will walk you through these results.
Thank you very much, Richard. First, a very brief overview of dry eye syndrome, or DES. This is a chronic inflammatory disease characterized by irritation and reduced tear production. It affects more than 16 million people in the U.S., has been increasing in incidence, but the reasons are not clear, but are at least in part environmental. DES is somewhat inadequately served by current therapies. Topical calcineurin inhibitors represent the mainstay of therapy for treatment of ocular surface disease. However, there is an unmet need for more effective drugs, and VOS is Aurinia's unique nanomicellar formulation that is being developed for treatment of dry eye disease. There are currently only three FDA-approved therapies for the treatment of DES, and these are RESTASIS
CEQUA and Xiidra. These products were approved based on the endpoints detailed in this slide. Both RESTASIS and CEQUA, a 10-millimeter increase in Schirmer score at six and three months, and more recently, Xiidra, corneal staining and eye dryness scores. You'll see that these outcome measures are important as I present the efficacy data from this trial in coming slides. Here is an outline of what these tests are and how they are performed. Both are objective measures of efficacy performed by the ophthalmologist. The Schirmer test is where the doctor places filter paper inside the lower eyelid and assesses how far the tear has traveled, giving an objective measure of tear production. Improving dry eye will lead to increased tear production. Corneal staining is where dye is introduced onto the surface of the eye. The dye stains problematic areas which appear green under blue light.
Damage is assessed according to extent of the staining. Here is a brief reminder of the study design. Subjects with DES were randomized to receive either VOS or RESTASIS. It's important to remind you at this point that this is an active control study comparing VOS with the approved standard of care. This double-masked exploratory study was powered, as Richard said, on expected drop discomfort scores. As we'll see in coming slides, hard objective measures of efficacy in dry eye symptoms, such as SANDE, were also assessed and reported. To summarize before we get into detail, VOS showed efficacy in multiple dimensions, consistently outperforming RESTASIS on important signs of dry eye syndrome, namely Schirmer test and corneal staining. Both VOS and RESTASIS patients also experienced significantly improved symptoms compared to baseline, too, and I'll take you through these exciting results on the next couple of slides.
The baseline characteristics are detailed on this slide, and of importance, they are well-balanced between the arms and are representative of the dry eye population in the U.S. Most subjects were post-menopausal women, and I'll draw your attention to the baseline SANDE scores. These scores are consistent with the more active end of moderate disease with respect to dry eye symptoms. The primary outcome measure of drop discomfort was assessed one minute after the first installation of the drug by way of VAS, Visual Analog Scale. Discomfort was between zero and 100 millimeters, with zero being no discomfort, 100 being the worst possible discomfort. You can see here that there was actually very little overall discomfort in either group, with minimal and non-significant difference between them.
It is important to note that initially, we expected 15-30 millimeters of discomfort, but in reality, we observed less than 10 millimeters. It is in the important efficacy endpoints that follow where things start to get interesting. When the Schirmer score was assessed, we found that VOS was statistically superior against the active comparator, RESTASIS, at nearly all time points. This chart details the mean change from baseline in Schirmer score for both eyes at weeks two and week four. Statistical significance was seen at multiple time points, improving over time from two weeks to four weeks. Again, just to remind you that this is an active comparator study. We are not aware of any other product that has shown superior results to the current standard of care in this disease. You can see an amplified treatment effect over time.
When we break down subjects by those who achieved a clinically meaningful improvement in Schirmer by greater or equal to 10 millimeters, and this incidentally, is the threshold required by the FDA for the RESTASIS approval, things become more interesting. More than 40% of VOS versus 18% of RESTASIS patients achieved this impressive endpoint. On the next slide, I'll show you how these response rates compare to those quoted in the package inserts for approved drugs in the class to give some context. It's helpful to look at this data in the context of potential commercial viability of VOS. While caution should always be used when we compare across studies, between 15% and 17% of subjects in the Cequa and RESTASIS studies achieved this 10 millimeter or greater improvement in their Schirmer score at 3-6 months. This proportion formed the basis of their approval.
On the right of your screen, you can see that in this study, the RESTASIS group achieved a comparable 18% response with respect to the proportion of patients getting greater or equal to 10 millimeters of increase in their Schirmer score. This is dwarfed by the 43% VOS response after only four weeks of therapy. The other critical objective in this disease is CFS or corneal staining. This is a well-accepted technique to show damage and scarring to cornea. Therefore, a reduction in the score represents a reduction in scarring. Again, when comparing against RESTASIS, we once again see that VOS was statistically superior, with dramatic declines in corneal staining being seen. The improvement in this measure appears to increase the longer patients are on VOS. This slide shows changes from baseline in corneal staining.
Again, at most time points, starting as early as a week after the start of therapy, we can see the profound reduction in staining in the VOS group compared to modest reductions being seen in the RESTASIS-treated patients. By week four, on the right of the chart, the difference is really quite pronounced. The SANDE score reduced significantly compared to baseline, although no difference was observed between the groups. SANDE is a scoring system that assesses the severity and also the frequency of symptoms in dry eye syndrome. This slide summarizes the safety observed in the study. There were no serious adverse events, and adverse events tended to be mild and expected for the condition. Visual acuity was assessed as a safety measure with improvements from baseline of both groups. No meaningful changes from baseline were observed in either slit lamp assessment or ophthalmoscopic examination.
In summary, we were extremely impressed with VOS in this study in terms of the superior efficacy for signs of dry eye symptom and dry eye syndrome, and improvements over baseline in these important but highly variable subjective symptom scores. Now I'm going to hand it back to Richard for some additional comments. Richard.
Well, thank you, Neil. Before I open it up for Q&A, I have a few final remarks. I believe these data indicate the significant potential for VOS in the treatment of dry eye. This study generated consistent, statistically significant, and clinically meaningful results for both signs and symptoms, and demonstrated the statistical superiority of VOS to RESTASIS on important efficacy parameters that have previously served the basis of FDA approval for other dry eye treatments. Based on these positive data, we plan to aggressively advance VOS for the treatment of dry eye syndrome. We believe we can create considerable value for both patients and our shareholders. With its own IP protection until 2031, we believe that VOS has the potential to become a leader in the dry eye treatment market, which is currently valued at over $2 billion, and where current treatments are marginal at best.
Our pursuit of further development of VOS provides the company with an enhanced pipeline that can capitalize on the differentiating features of voclosporin and positions us for substantial growth. We've learned a lot of valuable information from conducting this exploratory study. We look forward to sharing future plans on VOS development over the next few months. Before I actually move on to the Q&A, I'd like to ask Dr. Joseph Tauber, head of the Tauber Eye Center, to share his view on the data generated in the phase II study. Dr. Tauber?
I hope I'm audible. I was an investigator in this trial and have an over 25-year history of trial work in dry eye, having been involved in each of the RESTASIS studies, each of the Cequa studies, and quite a few other drugs that have not obtained approval. For me, this was an unusual study from the beginning in targeting post-installation discomfort. That's an endpoint that really has not been looked at in dry eye population. I think, in retrospect, I would describe that as an incorrect choice of parameter. The mainline parameters that we're all used to in dry eye studies are the ones that have already been discussed. From my point of view, frankly, the results are extraordinary, and in particular, in comparison with other studies that are out there for the drugs currently approved. I'm just going to repeat some of the things already mentioned.
The responder analysis, the improvement of 10 millimeters or more in Schirmer's testing, is more than 2 times higher than either drug that's on the market. That's never been reported before. An increase of 10 millimeters of Schirmer, speaking as a clinician, is an absolutely extraordinary degree of improvement to the point where Dr. Chambers has said, "If you just show that, you've cured this patient, I don't need to see anything else." That is the basis of approval for both Calcineurin inhibitors on the market. If you dig a little deeper into the fluorescein staining, the corneal staining scores on both RESTASIS and Xiidra, yes, they attained a statistically significant change from baseline versus placebo, it was perhaps on the order of a quarter of a unit. It didn't really reach the level of significance the FDA typically asks for, which is 1 unit.
That's why language like the totality of evidence was used in some prior approvals. The data in the Aurinia study, again, is extraordinary. There's greater than 1 unit change of improvement in corneal fluorescein staining at 1 week, more than 2 units at week 4. The trend appears to be increasing. That's an extraordinary improvement. The symptom endpoint in the study, again, I think was incorrectly chosen at SANDE, which has really never shown statistically significant separation between the drug and vehicle in prior studies.
I don't believe the individual symptom data was shown to you except for a summary table. I have had the opportunity to see that, and there were significant changes in virtually all individual symptom scores for VOS versus, in this case, RESTASIS, not even versus vehicle. For me, what I've seen in this not gigantic study so far is quite powerful demonstration of improvement in both symptom and sign. I would find this very exciting. I think looking at it as this study did not meet its primary endpoint is not the right way to look at it. I think looking at the data, I find them very powerful. I'll stop there.
Oh, no. Thank you very much for taking the time to be with us today actually to share those comments. I'm hoping you could stick around a little bit for the Q&A session. I understand you have some patients waiting for you, stay with us as long as you can. Okay. We're going to open it up now for Q&A. We'll start taking questions.
Thank you. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from the line of Ed Arce with H.C. Wainwright & Co. Please proceed with your question.
Hi. Thanks for taking my questions. Congrats on the unprecedented data in dry eye. A few questions for you. I can really appreciate here from the data how quickly the onset of action is, as shown in both of the measures for signs. As Dr. Tauber mentioned, the symptoms, the measures for symptoms, SANDE and VAS, were not statistically significant. I understand that there's a high degree of variability and perhaps some subjectibility with that. Perhaps if you could help us understand better what you saw and what your impressions overall in terms of the symptoms with VOS. Thank you.
Yeah. No, I think that's actually a fairly straightforward answer. I'll turn it over to clinicians to answer in a moment. I will say right off the bat that, in fact, your interpretation, I'm afraid, is actually incorrect. The SANDE scores, as well as other sort of symptom scores, were actually statistically significantly improved over baseline through the course of the study. What we said was that we weren't able to differentiate between improvements in RESTASIS versus improvements with VOS. Both provided very significant, statistically significant improvements over baseline. One of the things we find that highly variable symptomology type endpoints is that there's a great deal of variability to them. I believe that the longer you use the drug, the greater real data you'll generate. These early sort of four-week type studies may not give you the full picture.
Clearly, we're seeing tremendous improvements in, but I also think that has to do with lubricating the eye as well. I think they're useful in the longer term. I don't think in shorter term studies they're as effective as indicators. I repeat, both showed extremely significant reductions from baseline. Neil, any further comments?
Nothing particularly, but thanks, Richard. Ed, as Richard said, both showed a significant improvement in symptoms from baseline, but not significant difference between the two. I think what we can say in this study is that we showed an improvement in symptoms, albeit no different from RESTASIS, but also an improvement in signs, in contrast to what we've seen from the control arm, RESTASIS. This is as good as we could possibly have done.
This is Dr. Tauber. I just want to add a comment from the Cequa data. Cequa studies also showed a 30% reduction in patient symptoms from baseline and could not demonstrate separation from vehicle. This study is unique in comparing two actives without a vehicle. If subsequent phase III studies don't get the same magnitude placebo effect, this may prove significant, but it was equivalent to the prior work with Cequa.
Okay. Couple more follow-ups then, if I may. Again, the onset of action are clearly quite significantly better than RESTASIS. Wondering if this superior efficacy of VOS at four weeks could be, at least in part, a function of the short treatment duration versus RESTASIS. A last follow-up is, I know that you had intended to look at a number of other potential differentiators. Were there any assessment done on the potential for QD dosing versus BID? Thanks.
Okay. In terms of your first question, in terms of onset of action, I think you could keep in mind that we're actually comparing apples to apples in terms of what are the recommended doses. We actually moved forward with our drug relative to RESTASIS. RESTASIS was given the way it's meant to be prescribed. At four weeks, we assessed, as we did at two weeks and at four weeks, we assessed those scores. From an efficacy perspective, we clearly see that VOS far exceeded the performance of RESTASIS. I think it's very meaningful, these reductions that we're seeing. The reduction in RESTASIS was consistent with what we've seen historically in studies. Yet ours was consistently and considerably better throughout the entire study. I think it is very reflective of the difference. Now, keep in mind why this may be occurring.
When we deliver VOS, we're delivering four times as much drug to the eye. We're delivering a drug that's probably about four times more potent. If you're looking at calcineurin inhibition, you're delivering almost 16 times as much inhibition of calcineurin to the eye than you are with RESTASIS. It's not surprising to us that this drug would work faster, and we expect that kind of trend to continue in going forward. With respect to your second question, we have a partnership with Merck Animal Health. Merck Animal Health has actually allowed us to now begin to speak about some of the data they're generating.
One of the things they have shown clearly, in their studies, was both actually something very important, which is if you actually look at their study in terms of their timeline and how dogs react, because remember, that's where dry eye therapy started. It started with dogs and with Optimmune, their product, which is essentially RESTASIS. They compared the two directly. Their timeline on response in the dog was almost identical to what the human response looks like, which makes perfect sense. We had an indication. We were scared to use it as a primary outcome measure because everyone would thought we'd be crazy. We had an indication this drug was going to work quickly, and it sure did.
The other thing that was done with them is that they actually overlaid their studies with just a once a day formulation strategy, basically the same product but just given once a day, and actually almost virtually identical results. I actually believe what we have here, at the worst case scenario, is a non-inferior in terms of drop discomfort, and we have much, much higher efficacy and faster onset and the potential for a drug that could be dosed once a day. I think those are going to be important differentiators in moving this program forward. This was a guiding study. This was an exploratory study. This gave us great confidence on how to take the next step with this drug.
That's great, Richard. Thank you very much, and congrats again.
Oh, thanks. Thanks, Ed.
Thank you. Our next question comes from the line of Joseph Schwartz with SVB Leerink. Please proceed with your question.
Great. Thanks so much, and congrats on the positive data. I was just wondering if you could just expand a little bit on the low drop discomfort rate and if there are any hypotheses, either from the company or perhaps Dr. Tauber has some thoughts on that, and how much of an issue is that in the marketplace, Dr. Tauber. As you look at the emerging target product profile here, where do you think that a drug like this would fit in, that seemingly has a lot more efficacy?
I'm happy to answer. From the patient perspective, I think there are two reasons that we don't have a higher success rate with RESTASIS. The first is it doesn't create a highly perceptible patient improvement. Xiidra, by comparison, my experience, about 20% of patients say, "Wow, this is a great drug. I don't really care what it costs. I'm going to keep using it." No one says that about RESTASIS. I think it's more the slow onset of benefit that results in that patient evaluation compared to alternatives. For me, the onset of improvement and sustaining at one week really holds some promise that we may see a very different patient perception. The issue about discomfort from the drop, while it is widely reported at 15%, I'll just speak as a clinician, that's not the reason very many patients stop using that drug. Probably no more than 5%.
Discomfort is a factor. Cost is a very significant factor. In my experience, the time to onset of benefit and the limited perception of benefit are the bigger issues, and I think there's potential for this drug to get around that.
That's very helpful. Thank you. Just for the company, if you could lay out for us what you expect the next steps to be in development of VOS.
Okay. Joe, fair enough. Great. I think we're still assessing data, number 1. The data's only been fresh in our hands for two days, and we wanted to make sure it was available to our shareholders as quickly as possible. When we complete the assessment and analysis, we've already actually presented to the company's board of directors. We already have an endorsement from the board to be aggressive on moving this program forward and to fully fund a program. Keeping in mind, this study that we did was exploratory. We spent very little relative money to just see whether or not this drug actually deserved to be developed, and clearly it deserves to be developed. The next steps are developing the clinical program. I think we have opportunities to even further optimize the drug. I don't think it's actually going to take us that long.
We have drug supply, we have various dosing available for the drug, to move forward with. We've got the necessary tox data that we need in order to move forward with our next studies. I don't want to put out a timeline right yet today other than to say that we're actually well positioned to begin the next study fairly quickly. That said, we really want to evaluate very carefully, study design, take our learnings, and actually enhance the resources that are available to us in developing this further. I want to also make the point that we intend to take this further down the pipeline because we really do believe we can create significant value with this asset, and it's probably better for us to take it another step than it would be, for instance, to partner it out immediately.
We think that the development pathway is really clear. We know the regulatory pathway for the CNIs. It's actually fairly low risk for us. We really believe this is an asset we can create a tremendous amount of additional value without actually being particularly expensive. I could tell you, compared to doing a lupus nephritis trial, the access to patients, the speed with which we could do these trials, it's actually kind of enjoyable relative to the trudge work and the tough work we face in our LN program. We're not letting this asset go too quickly. We really believe there's too much value here that's untapped.
Sounds good. Congrats again.
Thank you.
Thanks.
Our next question comes from the line of David Martin with Bloom Burton & Co.. Please proceed with your question.
Thanks for taking my questions. The first one is, the formulation of VOS, your preclinical studies in the phase I that you did previously would've suggested this would've been better tolerated, given the known discomfort with RESTASIS. Why do you think you didn't see the difference in discomfort here?
I think it really starts off with the fact that we just didn't see the discomfort with the RESTASIS. Let's think of this in a couple of ways. First of all, if cyclosporine in RESTASIS, which is at half a percent or 0.05%, is the reason why. If it's the reason why there's discomfort when you apply it, and we're actually applying a drug which is actually four times as much drug actually being applied to the eye. If that's the case, then really, in a worst-case scenario, we're actually applying four times the amount of drug, getting the efficacy, and having similar levels of acceptable tolerability. That's the key here, and understanding really what tolerability means for this drug.
I think that's partly the case, but I also think that over a short period of time, it's really difficult in just four weeks to totally predict tolerability and comfort because I believe that over time, as the eye begins to heal, that you will actually see changes in symptomology and changes in how that tolerability works. I just don't think this study was designed well enough to be able to look at that longer term, and you have to keep in mind that both arms actually did really well, and it wasn't that patients were having a problem with both of these drugs. They just didn't have a problem with either of these drugs in the study.
Okay. The other thing is the RESTASIS actually didn't perform as well as VOS, but it performed better at four weeks than I think you would've expected the 18% getting the 10-millimeter improvement, whereas, in Phase III you saw 15% at six months. Why do you think RESTASIS performed better than expected here?
As we often say, it's difficult to compare study to study, and try to make them identical with parameters. I do think that the 18% is consistent with what you'd expect this drug to actually perform at as well. I also think that one of the issues is you just don't see a lot of data available at various time points to really go against. You are going a little bit blind, again, in terms of the timeframe and response in terms of what's available in the public domain. I think we're seeing a consistent response, basically, from RESTASIS, and I think that the increase, the significant increase above that, is actually a very real effect of actually having much greater calcineurin inhibition, much more greater, I think, inhibition of T-cell activation in the eye, given you're treating a T-cell-mediated disease.
Okay. This last question's for Dr. Tauber. You mentioned that Xiidra, it was impossible to differentiate between vehicle and drug when it came to symptom score, eye dryness. I'm wondering, is that going to be a necessary endpoint in the phase III for VOS, or have we moved beyond that, it'll be Schirmer and corneal staining?
You may have misheard me. My comment about failing to show separation in symptom scoring between active and placebo was Cequa, not for Xiidra. Xiidra is a rather powerful demonstration of symptomatic improvement. Yes, the FDA so far stands on two legs. You can demonstrate symptom and sign. Obviously, each can be an independent study, so it can be a package of four studies. Or this concept of return to normalcy, which Dr. Chambers has accepted on the basis of the Schirmer responder analysis and is at least open to total corneal fluorescein clearing, which no one has ever demonstrated. It is not necessary to do both symptom and sign. You have two drugs on the market that really didn't accomplish both, at least in a very powerful way. That's one answer.
I want to come back to just one previous thing, the comment about why did we see the question about the RESTASIS responder analysis at one month. Why is that so much better than what they had reported? Keep in mind, the RESTASIS use of that parameter was a post hoc analysis, and I think it's quite true they really were not permitted to comment about their data at anything other than the six-month time point. I think the earlier comment is exactly right. One last one about the drop installation discomfort, and it occurred to me as a clinical trial person, the way you ask a question really guides the answer.
If I ask you how often have you had headache, you have a rather high instance of saying, "Yes, I've had headaches." If we ask patients, "Has anything negative happened since we've seen you?" We get pretty spontaneous reporting. In this study, patients were asked, "Tell me how much discomfort you have." No one says zero, and I think that really was not the best constructed metric to look at what was intended to be looked at. I'll stop there.
Thank you.
Thank you, David.
Thank you. Our next question comes from the line of Douglas Miehm with RBC Capital Markets. Please proceed with your question.
Yeah, thank you. Richard, when it comes to the timing of events, I know you don't want to go into a lot of detail, but the next set of trials to support a final clinical program. Would you expect those next set of trials to start and last as long as this first trial that you just did and had the great results in?
No. My anticipation really fundamentally is that we've learned a lot from this first trial and that the next step is to actually be more aggressive, larger trial size and actually duration. Duration more consistent with what your approvable endpoints would be, sort of the three-month duration. As we progress, you could expect a much more standard program. I think you'll also see some dosing work being done by us, because we have different formulations and different dosing available to us, and actually study it. We'll do it simultaneously. I think that maybe 16 times the amount of calcineurin inhibition may be overkill. Maybe we only need eight. Maybe that leads to better tolerability.
I think that, while, as I focus on today, we didn't see a tolerability issue here overall in the real-world market, we do know that these people have sore eyes, and what you put in their eyes tend to bother them. We're going to do our best to see if we can even improve that further as we move forward. You'll see a fairly interesting, reasonably rapid determination of what our next steps are going to be. We will share those when we're ready to share those. A lot of the pieces we need to do all of those are actually already in place.
Okay. It'd be fair to say, based on the size of these trials, that perhaps the second half of 2020 is when you could start your final component, the phase III component of this drug?
I know you're trying to be able to figure out the modeling on this, and I appreciate that, but we really just don't feel comfortable yet in setting sort of expectations until we've really had a chance to take a look at what precisely the trial design needs to be and the timeframe for it. I think you will find us to be very aggressive. I think you will find us that we realize the value of time in driving this program forward. It won't be long. I will be able to answer that question openly. Just want to refrain till I think we really have done our homework.
Okay, that's fine. A quick question for Dr. Tauber. Maybe as it more relates to Xiidra, how would you compare, on the face of it, these results, recognizing their shortcomings, et cetera, versus what we saw come out of the Xiidra clinical results for ultimate positioning?
There were certainly some surprises in what we saw in the Xiidra trials and the Xiidra real-world clinical experience. From the trials, we were all concerned about the dysgeusia, the so-called bad taste that patients reported in trial. It's never been reported in any eye drop study. Real world, that's a non-issue. The complaints of discomfort from drop instillation in the study did not seem to be significant. Real world, that seems to be the largest reason patients stop using it. It's not the taste, it's the fact that it stings. In some cases, rather prominently. People have described it as, "This isn't just burning when you put in the drop. This is broken glass in your eye kind of burning." The people who won't take it because of drop-related discomfort are totally opposed to it. They think it's a horrible thing to ever do to a person.
On the flip side, 20% say, "This is great, and what this provides me is worth any price whatsoever." We've all learned not to take clinical trial experience as representative of what we'll see in the real world. The other perspective here, again, is the rapidity of onset of the benefit is striking. The strength of the response, and I'm, again, thinking about both the size of the fluorescein stain reduction and the responder analysis are outstanding compared to anything reported in literature.
If the company were to take it down from 16 times to eight times, would you see a commensurate decrease in efficacy in the staining or anything like that? Or do you believe that enough drug is getting into the eye where there's going to be negligible change as it relates to some of the outcomes that we saw here? I'll leave it there. Thanks.
I think the answer is, if we knew the answer, we wouldn't be doing the research. I don't have any scientific basis to answer to that.
Okay, perfect. Thank you.
Thank you.
Thank you, Doug.
Ladies and gentlemen, as a reminder, if you'd like to join the question queue, please press star one at this time. Our next question is a follow-up from the line of Ed Arce with H.C. Wainwright. Please proceed with your question.
Great, thanks for taking the follow-up. Just a couple of quick ones. First, Richard, I just wanted to confirm or further clarify a previous comment. Your intention is to continue to take this into at least a phase IIb sort of proof of concept yourselves before looking at potential partnering. Do you think you could take this all the way through to a registrational study? The second is along the registrational time point itself. Do you envision an ultimate pivotal study being either three or six months in duration? Thanks.
I think, for your second question first, I think classically, given the efficacy we're seeing and the time and the rapidity of response, three months with a nine-month follow-up from a safety perspective is probably what the regulators are going to be looking for. We'll confirm that with regulators as we go back. We did present a potential clinical plan earlier to regulators. I think that would be inconsistent. I think that we still need time to actually really confirm that. With respect to your first question, which is around partnering versus Any organization, and our job is to actually, as you know, and I truly respect shareholders' capital, is to respond. If someone is interested in owning this asset and is willing to pay the appropriate amount, of course, it's our fiduciary responsibility to look at that.
It's just that I think that by staying focused, putting our head down, investing in this product, we can create significant value. It's not particularly expensive. I don't see it as particularly risky. I don't see it as taking particularly long. I think patient access is really easy with 16 million patients in the U.S. It's got all the hallmarks of things that we could do relatively quickly. Where the real issue comes down to is what kind of commercialization organization do you need? I was joking the other day when I said that the kidneys are a long way from the eyeballs, and we really do focus on renal disease.
Ultimately, having a commercial partner, an ability to participate in the commercialization success of the drug, really, in my mind, means taking it further along the line, creating more value, and then being able to drive a better opportunity for our shareholders when we have the data to do so. Right now it's put our heads down, let's do the right trial. Someone comes and knocks on our door, we'll answer the door to see what they have to say. The reality is we're going to stay focused and actually create the value that I think is easily attained here.
That's very helpful. Thanks again.
Thank you.
Thank you. Our next question comes from the line of Louise Chen with Cantor Fitzgerald. Please proceed with your question.
Yes, thank you very much. Maybe a question for Dr. Tauber. Dr. Tauber, in what sense or in what measures do you believe that RESTASIS acted atypically? Whether it is the discomfort measurements or the symptom, the onset of the improvement in the SANDE score, for example, or what other aspects can you think of that we've seen RESTASIS digress from what you see in clinical practice?
Digression is a hard word, in part because the results with RESTASIS at these time points really haven't been reported before. The responder analysis results for RESTASIS seen at one month being equivalent to what was seen at six months. That came as a surprise to me. You can also read into this, comparing two different studies, which is always a challenge, but the percentage at one month being the same as what was seen at six months. Let's contrast that with what we see with VOS, where the responder analysis percentages, and again, I don't think this data was shared with you, but the percentage increases from one week to two weeks to four weeks. There's at least some reason to think that's continuing to trend upwards. That may represent some further promise here. Apart from that, I was not surprised.
RESTASIS performed, as I would have expected it would. I think perhaps there were fewer dropouts related to RESTASIS discomfort than in other studies, and that may in part be because of the investigators. We're all so used to that. When patients complain about some stinging, we kind of try to talk people through it. Clinically, there are things like refrigerate the drop and other strategies, but, certainly on our side, it's no longer a surprise where our first instinct is to say, "Well, you can drop out of the study whenever you want." We try to talk people to get through to the end. Apart from that, I was not terribly surprised by what I saw.
On the symptom improvement front, the kinetics of the response of RESTASIS, was that surprising how quickly it came on?
Boy, you're taking me back to 2003. I'm not sure that I remember the kinetics of the symptom improvement with RESTASIS from back then, and of course, they were very different parameters. My recollection may be that OSDI is what was used in RESTASIS studies, and that essentially failed. I don't know for sure that they scored individual symptoms in those studies. If necessary, I can get back to you on that. I'm sure I have that data available, just not at the tip of my fingers.
Thank you very much.
Thank you. Our next question comes from the line of David Martin with Bloom Burton & Company. Please proceed with your question.
two quick follow-ups. What were the discontinuations in both arms of the trial and discontinuations due to eye discomfort or drop discomfort in particular?
Thanks, David. There were very, very few discontinuations and none directly due to drop discomfort at all in the study. There were three discontinuations in total in the study due to dry eye symptoms.
Okay, last question. The phase IIb, will it be placebo-controlled, or will it be versus RESTASIS again?
Our understanding from a regulatory perspective, from an FDA perspective, is that we have to compare against vehicle in that study.
At least one study.
Yeah, in at least one study. Obviously, our thoughts on what we do in phase, whether we still put another study arm or not are still evolving.
Okay, thanks.
We actually think the data should be more profound. Okay.
Thank you. That concludes our question and answer session. I'll turn the floor back to Mr. Glickman for any final comments.
Okay. Well, thank you all for listening. Thank you for your questions. Thank you, Dr. Tauber, for staying online with us this morning. I think you could see, based on the data that's been generated, just how excited we really are and why we're excited. I think that we've learned a lot in this study. I think we have a real opportunity to take advantage of VOS and the differentiation we see of voclosporin in treating this disease. Over the next several months, we will be working very quickly and be able to come back to you and share with you our plans in terms of development of this drug and when we intend to initiate the next trial. Anyhow, once again, thank you all for attending this morning. Have a good day.
Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.