Q&A: A look at suprachoroidal avoralstat with Dilsher S. Dhoot at ASRS 2025

Photo of Dilsher S. Dhoot, MD, FASRS, at the ASRS 2025 meeting in Long Beach, California.

The American Society of Retina Specialists (ASRS) is holding their 2025 annual meeting in California. At this event, Modern Retina had the opportunity to speak with Dilsher S. Dhoot, MD, FASRS, from California Retina Consultants, Santa Barbara, California. In our conversation, he shared about early research into a potential treatment candidate for patients with diabetic macular edema (DME).

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

Modern Retina: You are presenting at this meeting. Can you share a bit about what you spoke about today?

Dilsher S. Dhoot, MD, FASRS: I'm here at is ASRS 2025, in Long Beach, California. It's a pleasure to be speaking today about avoralstat. What is avoralstat? Well, this is a plasma kallikrein inhibitor, and we look at avoralstat in a pre-clinical model, specifically the rabbit DL-AAA model. And what we showed today is that avoralstat is able to stop vascular leakage in this model. We're interested in avoralstat and this alternative pathway, because we know that patients with diabetic macular edema are not always responsive to VEGF inhibition. In fact, studies like protocol T show that up to 40% of patients can have residual diabetic edema and fluid. And so clearly, alternative pathways are involved, and one such pathway that has been implicated is the plasma kallikrein bradykinin pathway. Avoralstat is a small molecule. It's about 513 daltons, and is a potent inhibitor of the plasma kallikrein. And we've shown today that we can stop vascular leakage. We've shown that it's also durable with EC90 levels out to 6 months. And we also discussed, that the next step here will be a phase 1b trial, which is starting in Australia, actually. It will be a 3 by 3 dose escalation trial in recently diagnosed DME patients. So we're excited to see the results from that.

MR: Speaking to the potential phase 1b trial. Is there any timeline associated with that, or when that might sort of be?

Dhoot: Phase 1b trial has started to enroll already in Australia, and we hope to see some preliminary results by the end of the year [2025] and probably into the first quarter of next year [2026]. So very exciting times for this agent.

MR: As far as kind of, the state of macular edema and where things are at, how do you think this might change how we're treating things, or what the potential could look like for patients in the future?

Dhoot: We've had good success with anti-VEGF agents, but the reality is that there is a proportion of patients that don't respond, and so clearly there are alternative pathways involved. The plasma kallikrein bradykinin system is a distinct pathway from the VEGF pathway, and using new mechanisms action, we feel that potentially, with mono-therapy, a drug like this can be successful. Now, it's important to note that we've looked at plasma kallikrein inhibition in the retina space before, with other assets in other companies. It turns out, though, that though we've seen biologic activity, those trials did not meet their primary endpoint, and we feel that this may be potentially due to bioavailability of the drug in the patient population that was studied. And so we think that the suprachoroidal administration is a beneficial mode of administration, and we think that the small molecule has the ability to be in the retina for a long period of time, 6 months.