Clinical Studies:
ARCHWAY
Citation: Holekamp NM, Campochiaro PA, Chang MA, et al. Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2022;129(3):295-307.
Key Points
- Continuous ranibizumab delivery via an implanted, refillable Port Delivery System (PDS) refilled every 24 weeks, preserved vision and anatomy as well as monthly intravitreal ranibizumab injections.
- 98.4% of PDS eyes required no supplemental anti‑VEGF before the first refill.
- ≥85% of eyes lost <5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters; 80.6% retained visual acuities of 20/40 or better.
- Adverse ocular events of special interest occurred in 19.0% of patients in the PDS group compared to 6.0% of patients in the monthly ranibizumab group. Endophthalmitis occurred in 1.6% of PDS-treated eyes and 0% of the monthly ranibizumab-treated eyes. Overall systemic safety matched monthly injections.
Objective
To evaluate the safety and efficacy of the PDS with ranibizumab 100 mg/mL refilled every 24 weeks versus monthly ranibizumab 0.5 mg monthly intravitreal injections for the treatment of neovascular age-related macular degeneration (nAMD).
Study Design
Phase 3, pivotal, interventional, randomized, controlled, open-label, visual-acuity assessor-masked, multi-center non-inferiority and equivalence trial with 3:2 allocation of PDS to monthly intravitreal ranibizumab. Primary endpoint was mean best corrected visual acuity (BCVA) change at weeks 36 and 40.
Subjects
- Major Inclusion Criteria:
- Age ≥ 50 years with nAMD diagnosed within 9 months of screening
- Subjects must have had at least 3 prior anti-VEGF injections within 6 months with documented anatomic/visual response.
- Major Exclusion Criteria:
- Any prior treatments for nAMD in the study eye other than anti-VEGF
- Presence of subfoveal fibrosis or atrophy or other vision-limiting macular disease
- Active ocular infection or inflammation
Randomization Scheme/Study Interventions
- PDS Q24W (n = 248 subjects): Surgical implant pre‑filled with ranibizumab 100 mg/mL; in‑clinic refill–exchange every 24 weeks with monthly monitoring. Supplemental 0.5 mg ranibizumab rescue allowed per protocol.
- Monthly intravitreal ranibizumab injection (n = 167 subjects): Standard intravitreal ranibizumab 0.5 mg every 4 weeks.
Results (through Week 40)
- Mean BCVA change: 0 letters (PDS) vs +1 letter (monthly)
- Loss <5 letters: 85 % (PDS) vs 88 % (monthly)
- ≥20/40 vision: 81 % (PDS) vs 82 % (monthly)
- 98% of PDS-treated eyes required no supplemental injections before first refill
- Central point thickness change: +5 µm (PDS) vs +3 µm (monthly)
- Ocular adverse events of special interest: 19 % (PDS) vs 6 % (monthly); conjunctival bleb 6.5 %, vitreous hemorrhage 5 %, endophthalmitis 1.6 %, rhegmatogenous retinal detachment 0.8 % in PDS arm.
- Systemic serious adverse events and mortality balanced between arms
Conclusions
- The ARCHWAY trial demonstrated that a fixed 6‑month refill regimen of PDS‑ranibizumab sustains visual and anatomical outcomes equivalent to monthly injections while drastically reducing the intravitreal injection burden.
- Surgical implantation introduces distinct but manageable ocular risks, underscoring the need for meticulous technique and follow‑up. Overall, PDS offers a durable alternative for managing nAMD.