FDA Accepts Application for Genentech’s Port Delivery System with Ranibizumab (PDS) for Treatment of Wet AMD
Genentech announced that the FDA has accepted the company’s Biologics License Application (BLA), under Priority Review, for Port Delivery System with ranibizumab (PDS) for the treatment of wet age-related macular degeneration (AMD). If approved, PDS would be a first-of-its-kind therapeutic approach, offering people living with wet AMD an alternative to frequent eye injections of anti-vascular endothelial growth factor (VEGF), the current standard of care. The FDA is expected to make a decision on approval by Oct. 23, 2021.
“Anti-VEGF therapy brings significant benefit to people with wet AMD, but optimal results require frequent trips to the doctor’s office for eye injections. This burden leaves many people under-treated and susceptible to vision loss,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, said in a company news release. “If approved, PDS would transform wet AMD treatment by providing up to 6 months of uninterrupted therapy that could potentially improve vision outcomes compared to what is currently achieved in the clinic.”
PDS is a permanent refillable eye implant, approximately the size of a grain of rice, designed to continuously deliver a customized formulation of ranibizumab over a period of months, potentially reducing the treatment burden associated with frequent eye injections.
The BLA submission is based on positive results from the phase 3 Archway study primary analysis, which showed that of those wet AMD patients being treated with PDS, more than 98% were able to go 6 months without needing additional treatment prior to the refill exchange. In addition, these patients achieved vision outcomes equivalent to patients receiving monthly ranibizumab eye injections. In the study, PDS was generally well-tolerated, with a favorable benefit-risk profile. The safety profile of PDS in the clinical trial setting is well understood and will continue to be closely monitored. If approved, PDS would be the first and only wet AMD therapy indicated to allow 6 months between treatments.
Genentech has a robust phase 3 clinical development program underway for PDS, including the Portal, Pagoda and Pavilion studies. Portal is an extension study evaluating the long-term safety and efficacy of PDS in wet AMD. Pagoda is evaluating PDS for the treatment of diabetic macular edema (DME), while Pavilion is a study of PDS in diabetic retinopathy without DME. Both the Pagoda and Pavilion trials are actively recruiting participants.
The PDS Marketing Authorization Application has also been validated by the European Medicines Agency and is currently under review.
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 6 months at fixed intervals, compared to monthly intravitreal injections of ranibizumab 0.5 mg in 418 people living with wet AMD. 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.
According to pre-specified study criteria, PDS was shown to be noninferior and equivalent to monthly ranibizumab injections. On average, patients had received five prior ranibizumab injections before their first Archway visit. In the PDS arm of the study, patients gained an average of 0.2 eye chart letters in visual acuity from baseline compared with 0.5 eye chart letters for the monthly ranibizumab arm. During the first treatment interval, before the first scheduled refill, 1.6% of PDS patients assessed (n=4/246) received supplemental treatment, and 98.4% of patients (n=242/246) did not receive supplemental treatment.
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 at Week 36. In the study, PDS was generally well-tolerated, with a favorable benefit-risk profile. The safety profile of PDS in the clinical trial setting is well understood and will continue to be closely monitored.