The high treatment burden of AMD including frequent injections and office visits are severe limitations to achieving the optimal outcomes in neovascular AMD. Moreover, recent studies have demonstrated a high discontinuation rate of anti-VEGF therapy after the first year, and in light of the recent pandemic, finding sustained treatment delivery for all anti-VEGF mediated diseases is of paramount importance. Different strategies including gene therapies and inhibiting alternative pathways to anti-VEGF A are just some of the approaches being investigated.
The port delivery system allows for the surgical implantation of a reservoir into the eye which releases Ranibizumab into the vitreous cavity. The surgical procedure has been improved upon in previous clinical trials and the complications rates have significantly declined. Following the encouraging results of the phase 2 LADDER study, the ARCHWAY study in phase 3 evaluated the port delivery system (PDS) for sustained delivery of Ranibizumab versus monthly treatment. Patients who were considered responsive to anti-VEGF treatment for neovascular AMD were randomized to receiving the PDS with Ranibizumab versus Ranibizumab every 4 weeks for one year. The objective was to evaluate the equivalence in visual acuity in a previously treated neovascular AMD population.
The study demonstrated equivalent visual outcomes between the two groups. Impressively, 98.4% of patients did not receive a supplemental injection in the PDS group before the first refill exchange at 6 months. Complications of the surgical implant group included conjunctival thickening, vitreous hemorrhage following the surgical procedure (5.2%), conjunctival retraction or erosion (2.0-2.4%), and endophthalmitis (1.6%).
So is PDS ready for prime time and will it become the gold standard for AMD treatment? Being able to maintain patients on 6-month intervals of treatment is an impressive feat and will likely result in the most optimal treatment outcomes. The side effect profile is still certainly higher than a population of patients treated simply with office-based anti-VEGF injections so some patients and providers might not use PDS as first-line therapy. Besides, with 30% of anti-VEGF injectors being general ophthalmologists and not retina specialists, this surgical procedure is likely something they would not adopt. These studies are also only one year long so having multiple years of data would also be helpful to better understand the long-term safety profile of PDS. And are ophthalmologists willing to exchange a surgical procedure for the office-based reimbursement for on-going monitoring of neovascular AMD? That remains to be seen. A plausible treatment pathway is likely that the patient will receive a series of injections and only if demonstrating a high treatment burden (8-10 weeks or less between injections for example), PDS would be a viable alternative to decrease the burden and improve adherence to treatment.
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