Phase 3 SOL-1 trial results are a “landmark achievement” for investigational TKI therapy for wet AMD
Ophthalmology 360 spoke with Pravin Dugel, MD, executive chair, CEO, and President of Ocular Therapeutix about the company’s recent announcement about phase 3 trial results. The SOL-1 study, investigating a tyrosine kinase inhibitor (TKI) therapy for the treatment of wet age-related macular edema (AMD), showed superiority over an anti-VEGF therapy in this patient population.
Question:
Ocular Therapeutix recently announced news about its investigational agent AXPAXLI™ for the treatment of wet AMD. Can you talk about that?
Pravin Dugel, MD:
We had a conference call and a press release a few days ago where we announced that AXPAXLI™ had achieved superiority in terms of the SOL-1 trial results to Eylea. This, in our opinion, was a landmark achievement. This is the first time a drug has ever been shown to be superior to an anti-VEGF. Many have tried over the last 25 years or so, none have succeeded. Not only did AXPAXLI™ succeed, but AXPAXLI™ succeeded with a P value that we thought was impressively robust, and we’re very proud of that. Happy to discuss the details of that, but very importantly, this was a landmark achievement because it’s the first and only time that a drug has achieved superiority in a phase 3 study to an existent anti-VEGF.
Look, there are 2 problems that we’re trying to solve with AXPAXLI™. It’s important to mention that the first one is quite obvious. The second one may not be quite as obvious. The first problem that we’re trying to solve is that of sustainability. We know that there is a de-risk target that works, which is the suppression of VEGF. We’ve known this for decades. The results that the anti-VEGFs have achieved are nearly miraculous, but what we’re addressing is the tragedy of the fact that in this country alone, despite having these wonderful medications, despite knowing that there is a validated target, in the first year alone, the dropout rate is 40%. That’s just tragic. We’re addressing that with AXPAXLI™. The second thing that we’re also addressing, which is not quite as obvious, is the fact that even in those patients who are able to stay on this treatment, they inevitably end up losing vision, and they lose vision because of fibrosis and atrophy. That happens because of the pulsatile nature of our treatment.
The fact of it is that we’re talking about neural tissue that’s very much like having concussions on a regular basis, which causes fibrosis, atrophy, and loss of vision. We’re addressing both of those things, and the trial at this point is focused on showing that there’s sustainability with AXPAXLI™. What we have shown is a drug, which if we just talk about the drug and say, “Look, these are the parameters that’s been achieved,” in a very colloquial way, I think anybody, any retina specialist, would look at this and say, “Boy, if you have a drug with a single injection that is able to have patients rescue free, two-thirds of patients rescue free up to week 52, that in and of itself is going to be astonishing.”
Well, we have that. On top of that, if we were to say, look, the same drug also achieves a level of disease control measured by an objective measurement, which is the OCT that is within a 30 micron fluctuation, which nobody has shown before, a 30 micron fluctuation with a single injection at week 36, that’s an absolute grand slam.
That’s exactly what we’ve been able to show. It’s not just that a superiority achievement was announced with a P value that’s extremely robust, it’s all the clinically relevant data sets that we announced as well. I totally realize that what we have is a phenomenal regulatory endpoint, and the regulatory endpoint allows us to potentially get a superiority label that no one else has achieved for over a quarter century. That in and of itself is a landmark achievement, but from a practical sense, the fact that we are able to show things that are clinically relevant to physicians and patients that apply to real life, which is the difference in terms of the OCT rescues, the difference in terms of visual acuity that’s going to turn out to be the most relevant clinical factors.
Question:
TKIs are a new class of drugs being investigated for wet AMD treatment. How do TKIs differ from currently available treatment options for wet AMD?
Pravin Dugel, MD:
Yes, so it’s not just the TKI, it’s also the TKI in this particular platform, right? What we know about TKIs is that they’re pan-VEGF inhibitors. There’s a wide range of TKIs, and what we have with our TKI in AXPAXLI™ is a TKI that we know is the most potent and most specific suppressor of VEGF. At the end of the day, that’s what matters because that’s the de-risk target. We also have a platform that’s a hydrogel. It’s a tunable hydrogel, and we know that this is a hydrogel that will go away when the drug goes away. There’s no remnant that’s left behind. Everything that we’ve shown in this trial has proven that. We believe that the marriage of the 2 is what’s really important. From a regulatory point of view, look, the great thing that we have is that the TKI is approved already by the FDA. The hydrogel is already approved by the FDA, and that allows us a very efficient path forward from a regulatory point of view. That along with the fact that we have a SPA, along with the fact that yesterday, February 18, 2026, it was announced by the leaders of the FDA that they would allow for a single trial as a default to be submitted for approval, which is exactly in line with what we’ve been saying all along, I think allows us a very efficient path forward where we firmly believe that not only will we be best in class, but now specifically with what we’ve been saying and with the validation that we got, which is the editorial in The New England Journal of Medicine that was released last night, that not only will we be best in class, we’ll absolutely be first in class as well.
Question:
What is the estimated future timeline for the potential availability of AXPAXLI™ for this patient population?
Pravin Dugel, MD:
What we have committed to do is to get this drug to patients as quickly as possible with the editorial in The New England Journal of Medicine on February 18, which validates what we’ve been saying all along that we believe that we’re eligible to submit for approval with a single trial with SOL-1 alone. We have other efficiencies as well. For instance, as I said earlier on, this drug consists of 2 components. One is the TKI and the other is the hydrogel. Both of them are FDA-approved individually. That saves us a lot of time. We can submit through a pathway known as the 505(b)(2), which saves us at least 2 months in the front end. On the back end, we have a SPA, a special protocol agreement, which is the highest level of agreement that you can have with the FDA. It’s a contractual agreement.
They’ve already reviewed our statistics plan, they’ve already reviewed our clinical design, they’ve already reviewed the powering, etc. We believe that this filing will be very efficient. We have all the data that we need because what we’re not doing, very importantly, is we’re not slowing down or stopping the second trial known as SOL-R, which is a non-inferiority trial. That allows us a lot of flexibility. If the FDA, for instance, wants to see the results of redosing, remember that every patient who’s reached week 52 and is in the trial has been redosed. We have a lot of redosing information already in-house with SOL-1. It’s under masking, but that information is there.
There’s even more information with SOL-R. The FDA may say, “Look, the SOL-1 information is sufficient.” They may say, “We also want to see some of the SOL-R information either under masking or open up SOL-R.” We can do whatever it is that we want. What I can tell you is we’ve done a lot of work to make sure that we’re in the position that we’re in to be able to submit with a single study and get it very efficient approval. We’re more confident than ever, following that February 18 editorial and our engagement with the FDA, that we’ll be able to submit and get approval for this drug with SOL-1.
Question:
Is there anything else Ocular Therapeutix would like to share?
Pravin Dugel, MD:
Absolutely. The turnaround in this company with Ocular Therapeutix is, I believe, quite impressive. This is a company that has completely changed in 2 short years, and this has happened because of the team that we’ve assembled. What I’ve learned from this is is evident from this, is that when you bring just the best of the best of the best people and you create a culture where they can thrive, where they’re trusted, where they’re valued, and they can do what they do best, you can get results that are near miraculous. If you think of where this company was before this group came just a short 2 years ago to where we are now talking about doing something, this is historic that nobody’s been able to accomplish in a quarter centuries.
We’re a small company. There are wonderful, huge companies that have attempted to get over that barrier of a superiority trial. Nobody’s been able to do that. We have recruited a trial that everybody told us was not recruitable in a record time. We’ve done this with a great deal of integrity and a great deal of efficiency, and we’ve delivered the result that we said we’re going to deliver. We said, we’re going to deliver a superiority study, which is really a holy grail in our field because nobody’s been able to do that precisely because the anti-VEGFs are so very good.
To have a company in 2 years, have new people come in and reach the holy grail that nobody’s been able to do, not the enormously large companies that are very good, that have far more resources than we do, not the folks that have been trying for all this time for 25 years to achieve something that nobody’s been able to do, and to do it with a small company in a matter of 2 years, I think is quite remarkable. It’s a credit to the team. I credit to the folks that we have here, and most importantly, it’s a credit to the company culture that they’ve built.
Related Content
