At the American Society of Retina Specialists (ASRS) 2024 Meeting, an expert panel showcased the projected longevity and diverse applications of the ranibizumab port delivery system (PDS), discussing new updates to the device and delivering first readouts of results from the Pavilion, Pagoda, Archway, and Portal trials.
Updated PDS Addresses Septum Dislodgement Concerns
Dante Pieramici, MD, opened the discussion with a presentation on the updated PDS device, which underwent remodeling after its voluntary recall by Genentech in October 2022 due to concerns over the septum dislodging after repeated use. The new PDS has a reinforced bond between the septum and body of the device as well as additional lubrication on the refill needle that reduces insertion force by more than 50%. In a comparison study with the original device, the updated PDS showed 100% survival after 10 years of simulated use (21 punctures) vs only 47% survival in the original PDS, with similar results expected after >30 years of simulated use.
Phase 3 Trials Results Demonstrate Sustained Efficacy and Safety
The rest of the panel discussion was dedicated to sharing first readouts from ongoing phase 3 trials involving the PDS and discussing its applications for the future.
Margaret Chang, MD, MS, kicked off these discussions by sharing the 2-year results of the Pavilion trial, which investigated the use of the PDS for patients with treatment-naïve moderate-to-severe nonproliferative diabetic retinopathy. After 2 years, no new safety concerns were reported and 80.1% of patients in the PDS group maintained a ≥2-step Diabetic Retinopathy Severity Score (DRSS) improvement versus only 9.0% of control patients (standard-of-care monitoring every 4 weeks with supplemental treatments as needed). Furthermore, when control patients were implanted with the PDS at week 52 and followed through week 100, they showed similar significant gains to those seen in the original PDS patients.
Carl Awh, MD, FASRS, shared similar positive outcomes seen in the ongoing phase 3 Pagoda trial studying the use of the PDS for diabetic macular edema (DME). Two years post-implantation, the PDS continued to be noninferior to monthly injections for sustaining vision and reducing central subfield thickness, with >95% of patients in the PDS group not requiring supplemental treatment. As in the Pavilion Trial, control patients who crossed over from monthly injections to the PDS showed similar visual and anatomic responses, and no new safety concerns were reported.
Aleksandra Rachitskaya, MD, FASRS, discussed results from the Archway trial and Portal trial (an extension that includes patients from Archway or Ladder), which focus on the use of the PDS for neovascular AMD (nAMD). In patients who initially received the PDS and those who were switched to the PDS, use of the PDS resulted in sustained visual (BCVA) and anatomical (retinal fluid) changes that were comparable to those seen with monthly injections. Additionally, patient satisfaction was high, with 90% of patients reporting a preference for PDS over monthly injections.
The outcomes seen in these studies support the use of the PDS for continuous delivery of ranibizumab and demonstrate its potential to produce sustained patient outcomes while offering a decreased treatment burden.
Risk of Endophthalmitis Appears Very Low
Dr. Pieramici admits that despite these benefits, “there are still some hurdles” as to whether physicians will adopt the PDS. Some physicians have remaining concerns after the recall and are reluctant to trust the updated device. “The risk of endophthalmitis is likely holding back some folks.”
However, endophthalmitis does not appear to be a major concern across any of the longer-term clinical trials discussed in this symposium. In the Pavilion trial, for instance, no cases of endophthalmitis were reported until day 695, when 1 case was reported. In Dr. Chang’s opinion, “I think we’ve learned that the improved instructions for use . . . have decreased the rate of endophthalmitis cases.”
Similarly, no cases of endophthalmitis were reported until the second year of the Pagoda trial (4 cases), and all 3 of the patients with follow-up were successfully managed (improved or returned to their baseline vision).
“The rate is definitely not zero,” said Dr. Awh, explaining that the numbers are too small to get an accurate idea of what the true incidence is. “But in every successive study, the rate of endophthalmitis appears to have dropped considerably, [and] the biggest threat to vision is undertreatment. More vision is lost from undertreatment with intravitreal injections than from endophthalmitis.”
Even Patients Who May Not Need Long-Term Treatment Can Benefit
Another potential barrier to adoption of the PDS may be concerns over implanting a device in patients who might not require lifelong treatment, particularly when there are concerns over an association between long-term anti-VEGF therapy and an elevated risk of geographic atrophy.
In this case, several of the panelists reminded the audience that the PDS is a refillable drug-delivery service. Although the port is there, you don’t necessarily have to use it, and unlike some other therapies (e.g., gene therapy) it can easily be “turned off.” Dr. Chang noted that, “there may be other medicines in development that could [use the PDS] for other indications.” Panelists were in agreement that the future may likely involve a combination of therapies.
In general, given the stability updates to the PDS device, its demonstrated long-term efficacy and patient satisfaction, and potential indications for different ocular diseases, panelists were generally optimistic about the future of the PDS and hopeful that clinicians may become more willing to adopt this device for their patients.