Genentech announced detailed results from the phase 3 Archway study evaluating its investigational Port Delivery System with ranibizumab (PDS) for the treatment of wet age-related macular degeneration (AMD).
In Archway, 98.4% of PDS patients were able to go 6 months without needing additional treatment and achieved vision outcomes equivalent to patients receiving monthly ranibizumab eye injections, a current standard of care.2 In the study, PDS was generally well-tolerated, with a favorable benefit-risk profile.2
PDS is a permanent refillable eye implant, approximately the size of a grain of rice, which continuously delivers a customized formulation of ranibizumab over a period of months. PDS is the first wet AMD therapy to achieve positive phase III results for this extended length of time between treatments.3 These new data will be discussed virtually during the 38th Annual Meeting of the American Society of Retina Specialists (ASRS) on Sunday, July 26, 2020. A recorded presentation of these data is now available to ASRS attendees through the meeting web portal.
“Based on the Archway results, PDS could potentially reduce the number of treatments from as many as 12 per year to two per year for neovascular AMD patients, without sacrificing efficacy,” Carl Regillo, MD, Chief of Retina Service at Wills Eye Hospital in Philadelphia and an Archway study investigator, said in a company news release. “While effective therapies exist for this condition, I know from clinical experience that it can be difficult for patients and caregivers to commit to frequent treatments, and patients who are not treated frequently enough may be at risk of losing vision.”
The current standard of care for wet AMD requires patients to visit their ophthalmologist as often as monthly for eye injections of anti-vascular endothelial growth factor (VEGF) therapy to help maintain vision gains or prevent vision loss.4 This high treatment burden with anti-VEGF therapy can lead to under-treatment of wet AMD and, potentially, less than optimal vision outcomes.4,5
“For over a decade, we have been working to develop new treatments that better address the unmet needs of people living with neovascular AMD,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, said in the news release. “Based on these data, we believe that the continuous delivery mechanism enabled by PDS may offer effective, reliable results while also alleviating the treatment burden. We are excited to share the data with regulatory authorities with the aim of bringing this new treatment option to patients as soon as possible.”
Patients in Archway received either PDS refilled every 6 months with a customized formulation of ranibizumab or monthly ranibizumab 0.5 mg eye injections. Patients in the study had received prior treatment with anti-VEGF therapy and were confirmed anti-VEGF responders. The primary endpoint of the study measured the change from baseline in best-corrected visual acuity (BCVA) averaged over Week 36 and Week 40. In the PDS arm, patients gained an average of 0.2 eye chart letters in visual acuity from baseline, with 98.4% (n=244/248) of patients maintaining the fixed 6-month refill schedule within the first refill period. Patients treated monthly with ranibizumab injections gained an average of 0.5 letters in visual acuity from baseline. According to prespecified study criteria, PDS was shown to be noninferior and equivalent to monthly ranibizumab injections. In addition, PDS controlled retinal thickness as effectively as monthly ranibizumab, with patients in both arms achieving a mean change in center point thickness within 10 μm from baseline. Safety data from the study support a favorable benefit-risk profile for PDS. The PDS implant insertion surgery and refill-exchange procedures were generally well-tolerated by patients and the systemic safety of PDS was comparable to monthly ranibizumab injections.2
In addition to Archway, the Portal long-term extension study is investigating the long-term safety and tolerability of PDS for the treatment of wet AMD.6 PDS is also being studied in the phase III Pagoda trial for the treatment of diabetic macular edema. The Pagoda trial is actively recruiting patients.
Results from the Archway study will be submitted to health authorities around the world, including the FDA and the European Medicines Agency (EMA), for consideration of regulatory approval for the treatment of wet AMD.
About the Archway Study
Archway (NCT03677934) is a randomized, multicenter, open-label phase 3 study evaluating the efficacy and safety of Port Delivery System with ranibizumab (PDS), refilled every six months at fixed intervals, compared to monthly intravitreal injections of ranibizumab 0.5 mg in 418 people living with neovascular age-related macular degeneration (nAMD). Patients enrolled in Archway were responders to prior treatment with anti-vascular endothelial growth factor (VEGF) therapy. In both study arms, patients were treated with at least three anti-VEGF injections within the 6 months prior to their Archway screening visit. The primary endpoint of the study is the change in best-corrected visual acuity (BCVA) score from baseline at the average of week 36 and week 40. Secondary endpoints include safety; overall change in BCVA from baseline; and change from baseline in center point thickness over time.
1 Bright Focus Foundation. Age-Related Macular Degeneration: Facts & Figures. Available from: https://www.brightfocus.org/macular/article/age-related-macular-facts-figures. Accessed June 2020.
2 Campochiaro, P, et al. Primary Analysis Results of the Phase 3 Archway Trial of the Port Delivery System With Ranibizumab for Patients With Neovascular AMD. American Society of Retina Specialists Annual Meeting; 2020 Jul 24-26.
3 Genentech Data on File.
4 Holz FG, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. The British Journal of Ophthalmology. 2015;99:220-6.
5 Rao P, et al. Real-World Vision in Age-Related Macular Degeneration Patients Treated with Single Anti–VEGF Drug Type for 1 Year in the IRIS Registry. Ophthalmology. 2018;125:522-28.
6 ClinicalTrials.gov. Extension Study for the Port Delivery System With Ranibizumab (Portal). Available from: https://clinicaltrials.gov/ct2/show/NCT03683251. Accessed June 2020.
7 ClinicalTrials.gov. This Study Will Evaluate the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Participants With Diabetic Macular Edema Compared With Intravitreal Ranibizumab (Pagoda). Available from: https://clinicaltrials.gov/ct2/show/NCT04108156. Accessed June 2020.
8 ClinicalTrials.gov. A Phase III Study to Evaluate the Port Delivery System With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration (Archway) [Internet; cited 2020 June 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT03677934. Accessed June 2020.
9 BrightFocus Foundation. Macular Degeneration: Essential Facts. Available at: http://www.brightfocus.org/macular/news/macular-essential-facts. Accessed June 2020.
10 Wykoff, CC, et al. Optimizing anti-VEGF treatment outcomes for patients with neovascular age-related macular degeneration. Journal of Managed Care & Specialty Pharmacy, 2018; 24(2-a Suppl):S3-S15.