Digital Exclusive: A look at the Phase 1 HELIOS trial with Dilsher Dhoot, MD

(Image credit: AdobeStock/noombluesman)

Dilsher Dhoot, MD, sat down with Modern Retina to provide some insights on the phase 1 HELIOS trial, which he presented on during the 2024 ASRS meeting held in Stockholm, Sweden earlier in 2024.

Note: This interview transcript has been lightly edited for clarity.

Dilsher Dhoot, MD: I presented interim data from a study called HELIOS. Officially, the title [of my presentation] was, "Interim safety and efficacy results from the phase 1 HELIOS trial of sustained release axitinib implant, also known as OTX-TKI for non-proliferative diabetic retinopathy (NPDR). Diabetic retinopathy, as most retinal physicians know is a chronic, progressive, burdensome disease, and we know that there's a large body of level 1 data that shows that treating with anti-VEGF, in a regular fashion, can reduce progression of DRSS and also reduce vision threatening complications. But despite this growing body of data, it turns out that less than 1% of NPDR patients are treated with anti-VEGF therapy, and then the majority of retina specialists on fact, two-thirds do not recommend treating NPDR patients without diabetic macular edema (DME). Some of the reasons for this are probably because treatments can be unsustainable in this population due to the burden, and we know that there can be worse outcomes in eyes that have interrupted or reduced treatment after beginning treatment therapies.

So, OTX-TKI potentially fills an unmet need here in these diabetic retinopathy patients. So you know, firstly, what is OTX-TKI? Well, it's a combination of elutex technology, which is OTX, is proprietary bioresorbable polymer matrix, combined with the axitinib, which is a highly potent tyrosine kinase inhibitor (TKI) that has a high affinity for VEGF receptor 2 compared to other TKIs under investigation for ophthalmic use. OTX TKI is delivered via a single intravitreal 25 gauge injection and is designed for bioresorption. It is completely bioresorbable over 6 to 12 months and also is biologically effective over that same period of time. The Helios trial was a phase 1 study of OTX TKI in patients with moderately severe and severe NPDR that's level 47 and 53. It's a simple trial. Patients are randomized in a 2 to 1 fashion to receive either OTX-TKI at baseline or sham injection, and then followed for 52 weeks. At the ASRS [conference], I presented a 48-week interim data, and the primary outcome was safety and tolerability of OTX-TKI. Secondary outcomes were DRSS change, need for rescue vision, and central subfield thickness changes in OCT.

In terms of the results, the safety results were great. OTX-TKI was generally well-tolerated. We saw no ocular SAEs, no intraocular inflammation, iritis, vitritis, or visculitis. The drug was well-tolerated in terms of secondary outcomes and efficacy. In terms of DRSS at week 48 all the improvements were in the OTX-TKI arm.

In fact, 23.1% 2-step or greater improvement; 46.2% 1- and 2-step improvements; 0% improvement in the sham control. When it came to DRSS worsening, all the worsening was in the sham group. In fact, 25% of patients worsening in the sham group, compared to 0% worsening in the OTX-TKI group. Vision threatening complications are important to physicians and patients, and so we saw that there was 37.5% vision-threatening complications in the sham group at week 48, compared to 0% in the OTX-TKI arm.

At ASRS, I presented some data on diabetic macula edema (DME). In this trial, there were patients that had DME that was non-center-involving, and if we look specifically at these patients, we saw that in the OTX-TKI arm. We gave 6 examples of patients that had non-centered DME, all with improvement by week 48. This is further indicating the biological activity of this drug relative to the sham. To summarize, we saw in this data set that the OTX-TKI demonstrated DRSS stability, or improvement with durability through 48 weeks. We saw safety of OTX-TKI. In fact, it was generally well-tolerated, with no reported instance of intraocular inflammation.

Sydney M. Crago: How many participants were in this phase 1 trial?

DD: In total, there were 20 participants: 13 patients in the OTX-TKI arm, and 7 in the sham.

SMC: Were they all in 1 location, or were they spread out at several sites?

DD: This is multi-center trial, so there were several sites that were participated in this. In fact, there were 10 sites tota.

SMC: Obviously, we have 52-week data to come out, and then potentially some phase 2 trials. Could you talk a little bit about the future of this process?

DD: Yeah, I think that the results are provocative, right? First of all, you know, the safety profile is consistent with the phase 1, both of the phase 1 OTX-TKI trials in neovascular AMD, and so that's good to see. Secondly, the durability is compelling. I think that the sponsor is excited about this and taking this into the next phase, so that one day we may see this on the shelf in practice, and potentially allow for patients to have 1 or 2 injections per year. This would stabilize diabetic retinopathy, which would be fantastic for patients.

SMC: Can you speak to the reduction in treatment burden that a potential treatment like this would have?

DD: Yeah, so right now, a lot of these patients are not being treated. You know, current paradigm is to be reactive. There are patients out there without DME that do have significant diabetic retinopathy that are being followed. These patients are at risk for vision-threatening complications, which can ultimately affect quality of life for these patients. A treatment like this would be treating a population that is not currently being treated. Certainly, there is a potential treatment burden decreased compared to clinical trials, but the reality is that patients are not being treated. So this would allow for patients to be treated with 1 or 2 injections, and therefore be treated in a proactive fashion so that they can preserve vision.