Portal extension trial: PDS maintains visual and anatomic benefits over long term

Most patients (95%) with the PDS implanted did not need supplemental treatment before the refills, indicating the persistence and durability of the treatment.

Interim long-term safety and efficacy data for the Port Delivery System (PDS) with ranibizumab (Susvimo, Genentech) indicate that the device maintains the visual and anatomic outcomes over 3 years and beyond.

Moreover, patients with neovascular age-related macular degeneration (nAMD) prefer this treatment over monthly injections of anti-vascular endothelial growth factor drugs, according to David Eichenbaum, MD, who reported the findings of the Portal Extension Trial at the Angiogenesis, Exudation, and Degeneration 2022 virtual meeting. He is Director of Research, Retina Vitreous Associates of Florida, and Collaborative Associate Professor of Ophthalmology, Morsani College of Medicine at the University of South Florida, St. Petersburg.

A caveat is that 2% of patients in the extension study developed endophthalmitis associated with conjunctional erosion.

The PDS provides continuous delivery of 100 mg/ml of ranibizumab into the vitreous. The previous phase 2 Ladder and phase 3 Archway studies provided results that were comparable to monthly injections but without the enormous treatment burden.

The Portal Extension Trial includes patients with nAMD from the Ladder and Archway studies to determine the long-term safety of this treatment.

In the Ladder study, patients received the PDS and 1 of 3 doses (10, 40, or 100 mg/ml) that were refilled as needed or monthly injections. Archway patients were treated with PDS 100 mg/ml with fixed 24-week refills or exchanges or monthly injections. In the extension study, the patients are treated with the PDS every 24 weeks. The treatment efficacy was assessed for those who moved from the Ladder study to the Portal Extension Trial. Patients also completed a questionnaire regarding treatment preferences. The safety was determined by analysis of pooled data from all randomized to the PDS in the 3 clinical trials.

Extension Results

Eichenbaum reported that the mean center point thickness and the best-corrected visual acuity (BCVA) remained stable in the patients treated with PDS 100 mg/ml and in those who had been treated with monthly ranibizumab injections from baseline to month 48. The mean BCVA letter change was 0.1 in the PDS group and 2.3 in the monthly injection group.

The vast majority of patients, 95%, implanted with the PDS did not need supplemental treatment before the refills, indicating the persistence and durability of the treatment.

Most patients who had received monthly injections, that is, 92%, preferred the PDS after switching, with 88% having a very strong preference.

Safety

Between 22% and 24% of patients had an adverse event of special interest. The most frequently seen events of special interest, about 50%, were development of cataract; 2% of cases in the PDS population developed endophthalmitis. The patients who developed endophthalmitis had an association with conjunctival erosion and conjunctival retraction. Eight of the 11 patients who developed endophthalmitis had a concurrent conjunctival erosion; 7 of the patients maintained vision over 20/40 or better at the last follow-up and 4 had substantial visual loss. Seven of the 11 had the implant removed.

Most events of special interest occurred during the first 1 to 2 years of the study. However, conjunctival erosion continued throughout the study.

“The conjunctiva must be watched over the long term as well as being recognized and managed,” Eichenbaum emphasized.

Patients who had substantial vision loss, defined as 15 letters or more, had conjunctival erosion throughout the study.

He concluded, “The efficacy outcomes over the long term in the Portal Extension Trial are maintained, with the PDS 100 mg/ml demonstrating stable vision and anatomy. Every-4-week treatment durability and reduced treatment burden persist beyond the results of the phase 3 trial and the results in the extension study are similar. Long-term safety is well characterized and manageable; 2% of patients had endophthalmitis in the PDS population that was most often associated with conjunctival issues and exposure. Patients preferred the PDS, with 92% who switched from injections expressing a strong preference or fairly strong preference for the PDS at week 48.”