Q&A: Justis P. Ehlers, MD, on the phase 1 HELIOS trial for NPDR

Photo of Justis P. Ehlers, MD, FASRS during Eye Care Network virtual interview

Justis P. Ehlers, MD, FASRS, presented at the Retina Society meeting in Chicago, Illinois. His talk focused on the dara from the HELIOS phase 1 trial, exploring a novel treatment for non-proliferative diabetic retinopathy. The study investigated OTX-TKI, a sustained-release tyrosine kinase inhibitor, comparing its effects against a sham treatment. Researchers conducted an in-depth analysis of retinal vascular parameters, fluid dynamics, and leakage patterns, offering potential insights into a more effective and less frequent intervention for managing early-stage diabetic eye disease.

Note: The following conversation has been lightly edited for clarity.

Modern Retina: You shared data from the phase 1 HELIOS trial at the Retina Society meeting. Can you highlight the key takeaways from this presentation?

Justis P. Ehlers, MD, FASRS: Thanks so much for the opportunity to share on some of this exciting data that came out of the HELIOS trial. What we were able to present was an analysis from the HELIOS phase 1 trial looking at non-prolific diabetic retinopathy without center involving diabetic macular edema.

What this trial looked at was a comparison of sham to treatment with a single injection of OTX-TKI, and this is a single injection of axitinib that's on a sustained release platform that's a tyrosine kinase inhibitor that appears to have sustained drug delivery and effect, potentially with dosing at about every 6 to 12 months.
What this trial was initially looking at was obviously predominantly safety, as a phase 1 trial, which showed no safety signals, no signs of any intraocular inflammation, as well as looking at changes specifically for diabetic retinopathy.

What our study and analysis focused on in this presentation at Retina Society was a specific post-hoc analysis looking at various retinal vascular leakage and fluid parameters. So this included an advanced analysis of the spectral domain OCTs, where we did a fluid based assessment and compared in a mass fashion, those eyes in the sham group to the eyes that were treated with OTX-TKI.

What we found was, over the course of the study, those eyes in the sham group trended towards increased fluid, whereas those eyes in the OTX-TKI group showed actually sustained reduction of fluid over the course of the study. Now, again, these weren't center involving DME eyes, but this we looked across the entire macula cube. Additionally, we were able to do quantitative ultra-widefield angiography. Again, what we've seen in other studies is that leakage is really an important leading indicator of disease activity and risk for progression.

What we were able to do is evaluate the changes over time in the 2 groups, the sham group, compared to the eyes that got OTX-TKI. What we found was that in the sham group, we saw progressive increase in leakage compared to in the group that had OTX-TKI, an overall reduction. When we look at this, this was evaluated in ultra-widefield angiography, so this allowed us to even do regional assessments. You know, is the retinal periphery different than the macula, for example, and there was no really differences. We were seeing a pan-retinal effect related to the OTX-TKI injection.

What was very interesting is that we've seen in anti-VEGF trials, for example, dramatic reductions in leakage, but they're often only sustained from anywhere from 6 weeks to 3 months, sometimes a little bit longer. But in this study, what we found was that reduction was actually sustained over the course of the 12-month study, and this was also similar and corresponded to the fluid reduction that we see. So overall, these are certainly encouraging results. It's a very small study as a phase 1 study, and this was obviously a post-hoc, although it was masked, you know, during the image analysis process, but it certainly leaves us with some real opportunity to understand the impact of OTX-TKI in future studies, and is supporting the ongoing planning for additional, larger scale clinical trial evaluating this in diabetic eye disease.

MR: When we consider what this could mean for the future of treatment in these patients, what could this potential reduction of treatment burden look like?

Ehlers: Right now, when we look at non-proliferative diabetic retinopathy, it's currently a disease window of opportunity for us to intervene in a way that we aren't currently doing. Very few clinicians use anti-VEGF therapy, although clearly it impacts diabetic retinopathy severity, reduces leakage, reduces fluid, the treatment burden, as well as if you balance out the risks and the benefits, it currently is not something that most clinicians are using. At the same time, we know that particularly in the severe or non-prolific diabetic retinopathy group, there's a very clear risk of vision threatening complications and progression of disease. If we had a therapy that required treatment once a year, you know, for example, or what we don't know is, is this in any way resetting the recurrence of this? Could it be longer than once a year? So I think what we're going to learn in future trials is if we can have some sort of sustained treatment that is safe and can really reset the clock and the timing of when the risk for vision threatening complications occur, it really could be a major impact in the way we look at earlier stage disease and diabetic eye disease. I didn't mention this as part of the more primary focus of the original results of the HELIOS trials. They did show that there are no eyes developed vision threatening complications in the OTX-TKI group, compared to a reasonable number of eyes that went on to progress as expected, in the sham group.