Patients who were treated with CLS-TA were able to achieve ≥3 lines of visual acuity 47% of the time, compared to 15% of the patients who received sham treatment.
At the 36th annual meeting of the American Society of Retinal Specialists (ASRS) in Vancouver, British Columbia, MD Mag sat with Steven Yeh, MD, to talk about the findings of the phase 3 PEACHTREE trial, which he presented at the meeting.
Yeh spoke about the utilization of a hollow micro-needle to deliver corticosteroid medicines in the suprachoroidal space, in place of intravitreal or periocular injections, which can often lead to a dangerous increase in intraocular pressure. This method was utilized in the PEACHTREE study, which enrolled 160 patients, 96 of which were randomized to the treatment arm to receive a pair of 4.0 mg doses of suprachoroidal suspension of the corticosteroid triamcinolone acetonide (CLS-TA) 12 weeks apart, and 64 patients of which were randomized to undergo sham procedures at the same 12-week interval. The patients were evaluated every 4 weeks for a total of 24 weeks, and 97% (n = 155) of those enrolled saw the full evaluation period to completion.
The mean change from baseline in the CLS-TA arm was an improvement of 9.6 letters at week 4 and 13.7 letters at week 24, as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) score. In comparison, the control arm improved 1.2 letters and 2.9 letters at those respective time points.
In a secondary endpoint, the administration of suprachoroidal CLS-TA resulted in an average reduction of 157 microns in central subfield thickness from baseline at week 24, compared to a 19-micron reduction in the sham cohort (P <.001).
Steven Yeh, MD:
The primary mode of delivery for corticosteroids to the eye is either directly into the eye as an intravitreal injection or outside the eye, in what's called a periocular injection. But we know that, particularly in uveitis patients, that with intravitreal corticosteroids, the rates of corticosteroid-associated elevations in eye pressure—intraocular pressure—can vary anywhere from 25% to as high as 90%, with some corticosteroid delivery systems.
So the thought that, again, through leading work done by [the late] Henry Edelhauser, PhD, at Emory University and Georgia Tech by Mark Prausnitz, PhD—the theory was that using a hollow microneedle, medication could be delivered into this potential space for the first time, and essentially give high levels of drug to the areas that mattered the most. These were areas like the retina, the retinal pigment epithelium, and the choroid for this disease indication [of macular edema associated with non-infectious uveitis].
So there was quite a bit of basic science work that actually showed that this was feasible, and this was found to be true in phase 1 and phase 2 trials, where suprachoroidal medication was able to be delivered and also the patients were able to derive benefit, as well, from this medication.
The PEACHTREE study was a phase 3, multicenter, randomized, controlled trial that looked at the delivery of suprachoroidal CLS-TA for the treatment of non-infectious uveitis in patients who had macular edema, or retinal swelling. The primary metric for patients who were treated with 2 injections of CLS-TA at the day 0 and the week 12 time point was the ability to improve visual acuity by 3 lines of vision or greater. What we found in the patients who were treated with CLS-TA was that 47% of patients were able to achieve 3 lines or better of visual acuity, when compared to 15% of the patients who received sham treatment (P <.001).
Besides the efficacy signals, which were very encouraging, we also looked at safety in the PEACHTREE study, and what we found was that when we looked at intraocular pressure elevation when patients were receiving suprachoroidal CLS-TA, intraocular pressure was actually very favorable in the study. When we think about the way that we deliver corticosteroids for the treatment of non-infectious uveitis, in the literature and in clinical practice, there can significant rates of intraocular pressure elevation with the currently available corticosteroid delivery mechanisms, including both the clinically-based procedures as well as the surgical procedures. The rates of corticosteroid-associated elevations intraocular pressure, [again] range from 25% to 90%, which is quite high. Becuase of that, we feel that CLS-TA, because of its lower rate of the rates of corticosteroid-associated intraocular pressure, has definite potential in the future for the treatment of macular edema associated with non-infectious uveitis, both due to its efficacy and the safety profile.
Transcript edited for clarity.
Related Coverage >>>