PDS implant matches monthly injections in efficacy in DME treatment

(Image credit: AdobeStock/Diana Vyshniakova)

The Pagoda randomized clinical trial (NCT04108156), which compared the results of treatment via implantation of the Port Delivery System (PDS) with ranibizumab (Susvimo, Genentech) and monthly injections of ranibizumab (Lucentis, Genentech) to treat diabetic macular edema (DME), found that the visual acuity (VA) with both approaches was comparable and the device was efficacious and safe,¹ according to Arshad M. Khanani, MD, and colleagues. He is from the University of Nevada, Reno School of Medicine, and Sierra Eye Associates, both in Reno, NV.

“Intravitreal anti–vascular endothelial growth factor (VEGF) injections have demonstrated efficacy in improving vision outcomes and quality of life for patients with DME.^2-7 Frequent treatment is required for optimal outcomes, with injections needed as often as monthly,^8,9 placing burden on patients, caregivers, and health professionals.¹⁰ Real-world data suggest poor adherence, with patients receiving fewer injections and worse vision outcomes than in clinical trials.¹¹ There is a need for strategies that maximize the clinical benefits of anti-VEGF therapy while reducing treatment burden,” the Pagoda study researchers explained.

The purpose of this study was to determine if continuous delivery of ranibizumab 100 mg/mL using the PDS with refill exchanges every 24 weeks provides noninferior outcomes through 64 weeks compared with monthly intravitreal injections of ranibizumab, 0.5 mg, in patients with DME.

Pagoda study design and results

This phase 3, multicenter, noninferiority trial was carried out at 87 US sites in patients with center-involved DME who had not been treated previously. They were randomized 3:2 to receive 4 monthly doses of ranibizumab, 0.5 mg, followed by ranibizumab, 100 mg/mL, via PDS every 24 weeks or monthly ranibizumab, the study authors recounted.

The primary study end point was the change in the best-corrected VA (BCVA) from baseline averaged over weeks 60 and 64.

The authors reported that 634 patients (57.3% men; mean age, 60.7 years) participated in the study and were randomized as follows: 381 to the PDS every-24-week group and 253 to the monthly ranibizumab group.

The mean change in the BCVA in the PDS group was a 9.6-letter increase and that in the monthly ranibizumab group was a 9.4-letter increase; these changes were averaged over weeks 60 and 64. The results met the primary end point of noninferiority for PDS delivery of ranibizumab.

The PDS group experienced a 6.7-letter BCVA decrease 4 weeks after the PDS was inserted. After 16 weeks, the mean BCVA in the PDS group was similar to that achieved with monthly ranibizumab, the researchers reported.

They also reported that adverse events occurred more often in the PDS group (27.5%) compared with the the monthly ranibizumab group (8.9%). No cases of endophthalmitis or retinal detachment were reported in associated with the PDS insertion. The most frequently occurring adverse events were cataract formation, vitreous hemorrhage, conjunctival bleb/conjunctival filtering bleb leakage, and conjunctival erosion or retraction.

In addition to comparable BCVA levels, the researchers concluded that the PDS implant “provides effective, durable, and generally well-tolerated treatment for DME with retreatment every 6 months through at least 64 weeks and was approved in the US for patients with DME in February 2025.”

References

1. Khanani AM, Campochiaro PA, Graff JM, et al. Continuous ranibizumab via Port Delivery System vs monthly ranibizumab: The Pagoda randomized clinical trial. JAMA Ophthalmol. 2025;Published online March 6, 2025. doi:10.1001/jamaophthalmol.2025.0006

2. Bressler SB, Liu D, Glassman AR, et al; Diabetic Retinopathy Clinical Research Network. Change in diabetic retinopathy through 2 years: secondary analysis of a randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab. JAMA Ophthalmol. 2017;135:558-568. doi:10.1001/jamaophthalmol.2017.0821

3. Brown DM, Nguyen QD, Marcus DM, et al; RIDE and RISE Research Group. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology. 2013;120:2013-2022. doi:10.1016/j.ophtha.2013.02.034

4. Brown DM, Schmidt-Erfurth U, Do DV, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology. 2015;122:2044-2052. doi:10.1016/j.ophtha.2015.06.017

5. Brown DM, Wykoff CC, Boyer D, et al. Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy: results from the PANORAMA randomized clinical trial. JAMA Ophthalmol. 2021;139:946-955. doi:10.1001/jamaophthalmol.2021.2809

6. Nguyen QD, Brown DM, Marcus DM, et al; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789-801. doi:10.1016/j.ophtha.2011.12.039

7. Wolfram C, Pfeiffer N, Hudde T, et al. Anti-VEGF preserves quality of life: results from the ALBATROS real-world data collection from Germany [abstract]. Invest Ophthalmol Vis Sci. 2023;64:4225.

8. Lucentis. Prescribing information. Genentech, Inc; 2024.

9. Eylea. Prescribing information. Regeneron Pharmaceuticals, Inc; 2023.

10. Sivaprasad S, Oyetunde S. Impact of injection therapy on retinal patients with diabetic macular edema or retinal vein occlusion. Clin Ophthalmol. 2016;10:939-946. doi:10.2147/OPTH.S100168

11. Ciulla TA, Pollack JS, Williams DF. Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28 658 patient eyes. Br J Ophthalmol. 2021;105:216-221. doi:10.1136/bjophthalmol-2020-315933