MONTREAL -- Patients with diabetic macular edema (DME) maintained improvements in visual acuity and retinal anatomy for up to 4 years with the ranibizumab port delivery system (PDS; Susvimo), according to updated results from a randomized trial.
After 208 weeks of follow-up, patients initially assigned to the PDS had a 9.4-letter improvement from baseline in best corrected visual acuity (BCVA) and a 211-µm decrease in baseline central subfield thickness (CST). About half of the patients had at least a two-step improvement in the Diabetic Retinopathy Severity Scale (DRSS). Patients who switched from monthly intravitreal ranibizumab (Lucentis) to the PDS at 64 weeks had similar improvement in BCVA, CST, and DRSS. Ocular adverse events were well defined and manageable, with no new safety signals during long-term follow-up.
During treatment with the PDS, 95% of patients required no supplemental anti-VEGF therapy outside of the 6-month device refill interval, reported Luke Lindsell, OD, MD, of the Cincinnati Eye Institute, at the American Society of Retina Specialists meeting.
"Continuous anti-VEGF delivery via the PDS platform has the potential to transform the care of patients with DME by preserving vision and reducing treatment burden," said Lindsell. "Approximately 75% of patients in all treatment groups were able to regain and preserve driving-level vision, which is critical in this predominantly working-age group."
Results from the so-called PAGODA trial also provided an answer to a question related to storage of biological agents.
"I love the PDS data," said Charles Wykoff, MD, PhD, of Retina Consultants of Texas in Houston. "The data I like most is that you can store a biologic at body temperature for months, even over a year, and it's still biologically active."
The PDS points to one potential solution to the conundrum retina specialists face with regard to diabetic eye disease, which often is not treated until progression or development of adverse events. No single agent or strategy will likely solve the problem, Wykoff continued. A continuous-release device, implants embedded with tyrosine kinase inhibitors, the tarcocimab anti-VEGF/biopolymer implant, or maybe even an oral therapy or eye drops all might have a place in controlling the disease without the treatment burden imposed by frequent intravitreal injections.
In response to a question, Lindsell said he uses the PDS "as much as I can" in his own clinical practice, outside of clinical trials.
"I have a lot of patients that I've moved out of the original clinical trials who are receiving fellow-eye treatment with standard of care, and all of them have asked to have the device put in their fellow eye," he said.
All patients in the PAGODA trial had received intravitreal injections prior to insertion of the PDS, Lindsell added. A survey during the trial showed that 80% to 90% of patients preferred the PDS with 6-month refill interval over more frequent intravitreal injections.
In response to another question about patient selection, Lindsell said patients who require frequent intravitreal injections are high priority for the PDS. Also, patients who do not live in one location year-round are good candidates for the PDS.
"For patients who don't want to see another provider, having a device that gives 95% of them good control over 6 months [is appealing]," he said. "I have had patients who just randomly did not come back, and I see them 10 months later and they're still dry."
Wykoff agreed that patients like the device but he uses the device sparingly in his own practice.
"I do talk to patients about it, but there is a risk," he said. "I think we've mitigated that risk by optimizing the surgical technique, but you're still raising the conjunctiva, and the chronic movement of the eyelid across that zone does, I think, create a long-term risk for potential exposure and associated risks. When there's a black box warning on the package insert, that does change the conversation with patients."
The PAGODA trial in DME evaluated the safety and efficacy of the 100 mg/mL PDS with refill every 24 weeks as compared with monthly intravitreal injections (634 patients, 3:2 randomization). Statistically powered for noninferiority, the trial met the primary endpoint of BCVA at 64 weeks. At that point, patients in the control arm switched over to the PDS.
Patients who received the PDS upfront and those who switched after 64 weeks had a transient decrease in BCVA immediately after insertion of the device, but vision quickly recovered and remained stable through 208 weeks, said Lindsell. At the end of follow-up, 75.4% of patients in the PDS arm and 72.2% in the switch group had 20/40 vision or better.
Safety data for 559 patients who received the PDS showed that the most common adverse events (all grades) were cataract (27.0% of patients), subconjunctival fibrosis/fluid (13.8%), and vitreous hemorrhage (11.3%). Serious adverse events occurred in 8.1% of patients, most commonly conjunctival erosion (2.1%), subconjunctival fibrosis/fluid (1.6%), cataract (1.4%), vitreous hemorrhage (1.4%), and endophthalmitis (1.1%).