Clinical Trials at the Summit 2023: Long-term outcomes with PDS for wet AMD

Arshad M. Khanani, MD, MA, MASRS, discusses long-term outcomes with the port delivery system for patients with neovascular age-related macular degeneration with Sheryl Stevenson, group editorial director, during the Clinical Trials at the Summit meeting on June 10, 2023, in Park City, Utah. Khanani is director of clinical research at Sierra Eye Associates in Reno, Nevada.

Video transcript

Editor’s note: This transcript has been edited for clarity.

Sheryl Stevenson: We're joined today by Dr. Arshad Khanani, who will be presenting at this year's Clinical Trials at the Summit in Park City, Utah. Welcome to you, Dr. Khanani. We're delighted to have you. [We're] so interested in hearing more about your talk regarding the long-term outcomes of patients with PDS [port delivery system] for wet AMD [age-related macular degeneration]. Can you tell us a bit about that?

Arshad M. Khanani, MD, MA, FASRS: Thank you, Sheryl, for inviting me to give a summary of my talk. I talked about long-term safety and efficacy of the PDS with ranibizumab in patients with neovascular AMD. I shared the results from the Portal 5-year subgroup analysis.

As practicing physicians, we know that in the real world and in extension of clinical trials, we have seen patients losing vision over time. Here, we were trying to see that with continuous delivery of ranibizumab can we have stable visual acuity for our patients. In this analysis, we looked at patients who were enrolled in the extension Portal study from the original Ladder study. As you recall, Ladder was a phase 2 program that looked at efficacy of PDS at three different dose levels compared to ranibizumab monthly injections. In the Portal study, patients who received injections in Ladder also received port delivery systems. We had 190 patients that were implanted in the original Ladder study, and then here looking at the efficacy population and with a few dropouts, we have a patient population of 124 patients that actually continue treatment for over 5 years in the Portal extension.

So [the] main thing, obviously, is looking at visual acuity. Remember, these were previously treated patients so we were expecting stabilization of visual acuity, not an improvement. What we saw in this analysis is that the baseline visual acuity of 20/40 was maintained over 5 years, so over 60 months in patients who receive the PDS 100 milligram per ml with every 6 months, or every 24-week refill. So pretty exciting to see that we are able to maintain visual acuity long term in these patients with sustained delivery.

The other thing we looked at was anatomy. This was evaluated using center point thickness, or CPT. What we saw was CPT remains stable again over 5 years, over 60 months, in patients who receive the PDS 100 milligram per ml and of course that's the approved PDS now...with every 6-month refill.

The other interesting thing was that approximately 95% of PDS patients who were implanted in the Ladder study or extension had a follow up over 5 years previously did not receive supplemental treatment through each refill exchange interval during Portal. As you recall, patients can receive supplemental injection treatment 4 or 5 months after the last refill or 1 or 2 months before the next refill.

Here we have [the] majority of the patients not requiring any supplemental treatment, again, speaks to the benefit of sustained delivery in stabilization of disease. Obviously, looking at adverse event is important. It's a study that we have an implant [and] we want to follow these patients for long-term safety. When we looked at these events in patients who had over 5 years of follow up, the number one event that had the highest percent was cataract formation, which was 27.2% of these patients. Again, this is unrelated to PDS. It's just progression of cataract over time because these patients are elderly with neovascular AMD. We also saw 6.1% rate of conjunctival bleb or conjunctival filtering bleb leak; 7% vitreous hemorrhage. We did not see any endophthalmitis in this long-term extension again, these are patients who have been followed over 5 years. They were from Ladder going to Portal and we had an [n =] of 114 patients.

In summary, looking at efficacy outcomes with PDS, what we saw was PDS 100 milligram per ml demonstrated stable BCVA [best-corrected visual acuity] and CPT from Ladder baseline to Portal data cut, which is 60 months from implant insertion procedure. We saw excellent durability of treatment with the decreased treatment burden where 95% of patients did not require supplemental treatment between each refill exchange cycle. Long-term data for PDS in terms of safety show that the safety profile is well characterized and manageable and it was well tolerated over 5 years. Thank you very much for your attention.

Stevenson: Excellent. A follow-up question: What are the main takeaways for the clinician to be able to put into their practice on Monday morning?

Khanani: So I think the main thing here is that obviously, currently, PDS was voluntarily recalled. We hope that PDS will be available in the near future. I think this data shows that for the first time in a clinical trial patient population that we have maintenance of visual acuity for over 5 years. So [for] patients who are coming into your clinic with neovascular AMD, once PDS is available, it may be an option for a subset of patients who don't want to get injections or get frequent injections.

We know the real-world data that over time, patients lose vision in the real world because of suboptimal treatment. Here we have an opportunity with [the] port delivery system to help these patients maintain vision over time, with only 6 months' refill exchange procedures. Of course, it's a surgical procedure. The safety profile is different, so we have to discuss the risks and benefits with each patient, and with proper surgical technique we may be able to help a lot of patients maintain vision long term with the port delivery system.