Dr. Kaiser: A phase 2 study of OTT166 is in the early stages of enrollment. We may not see a readout until next year. What is important to know about this study?
Dr. Boyer: The phase 2 study is a multicenter, randomized, double-masked, placebo-controlled trial in eyes with moderately severe to severe NPDR to mild PDR, and no center-involved DME. The primary endpoint is a 2-step or greater improvement in DRSS at 24 weeks. The study will also look at some key secondary endpoints, including the prevention of progression to sight-threatening complications, delaying the time to intravitreal injection and/or PRP, and some exploratory imaging endpoints that could help shape our understanding of DR.
Dr. Baumal: The concept of a topically applied treatment that prevents DR progression and may yield regression of DRSS in eyes with NPDR warrants interest. We hear often about potential paradigm shifts, and they do not always pan out. With OTT166, the early data are very promising. The phase 2 results will tell us more of the story. If this molecule can be successfully developed, however, we would have a treatment that represents a huge improvement over the current preferred practice of watchful waiting of severe NPDR. We could treat patients proactively instead of passively monitoring them.
Dr. Heier: There is clinical potential beyond DR, as well. In the phase 1, there were some promising outcomes in eyes with AMD. Whether this is a safe and effective monotherapy or adjunctive therapy in AMD is a question for later down the line, but the concept of targeting multiple pathways makes sense. We’re already seeing the proof-of-concept in that with Ang2-targeting agents.
Dr. Kaiser: As with all development programs, cautious optimism is warranted. The potential to offer patients with NPDR an easy self-administered, topical therapy that could reduce DR progression, or even regression, is an idea that could transform DR management. We have evidence that OTT166 reaches the retina in therapeutic levels, early confirmation of benefit from a phase 1 study, and now we await results from a crucial phase 2 study. If the data come back positive, we are on the precipice of a true paradigm shift in decision-making for patients with early-stage DR: we could potentially be entering an era of active, noninvasive, and proactive treatment, instead of monitoring as a default because of the myriad issues with current treatment options.
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