Primary Analysis Results of the Phase 3 Archway Trial of the Port Delivery System With Ranibizumab(PDS) for Patients With Neovascular AMD

Authors: Raman Tuli, Peter A. Campochiaro, Natasha Singh, David Kardatzke, Steven Blotner, Shienal Patel, Giulio Barteselli.

Disclosure Block: R. Tuli: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Hoffmann La Roche. Any direct financial payments including receipt of honoraria; Description of relationship(s); Consultant. Funded grants or clinical trials; Name of for-profit or not-for-profit organization(s); Novartis, Hoffmann La Roche, Apellis. Funded grants or clinical trials; Description of relationship(s); Clinical Trials , TENAYA, KESTREL, RAPTOR, RAVEN. •.A. Campochiaro: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); Aerpio, Allegro, Applied Genetic Technologies Corporation, Exonate, Genentech, Inc., Merck; Consultant, honoraria (C, H): Alimera, Allergan, Applied Genetic Technologies Corporation, AsclepiX, , Aste. •. Singh: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); Genentech. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee. D. Kardatzke: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); Genentech. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee. S. Blotner: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); Genentech. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee. S. Patel: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); Genentech. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee. G. Barteselli: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); Genentech. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee.

Purpose: In pts with nAMD, real-world analyses show that visual outcomes are worse than in clinical trials, in part due to the high treatment burden of frequent anti-VEGF injections. The PDS is an investigational drug delivery system for the continuous intravitreal delivery of a customized formulation of ranibizumab (RBZ). The Archway phase 3 trial is evaluating the safety and efficacy of the PDS for nAMD.
Study Design: Archway (NCT03677034) is an ongoing, phase 3, randomized, active treatment-controlled trial.
Methods: Archway (NCT03677934) is an ongoing, phase 3, randomized, active treatment-controlled trial. Eligible pts had nAMD diagnosed within 9 months of screening and were responsive to anti-VEGF therapy. Pts were randomized 3:2 to treatment with PDS with RBZ 100 mg/mL with fixed 24-week (Q24W) refill-exchanges or intravitreal RBZ 0.5 mg injections every 4 weeks (Q4W). The trial evaluated the noninferiority (NI) and equivalence of PDS 100 mg/mL Q24W versus RBZ 0.5 mg Q4W; the primary endpoint was change in BCVA score from baseline (BL) averaged over weeks (W) 36 and 40 (NI margin, -4.5 letters; equivalence margin, ±4.5 letters). Primary analysis results with data through W40 are reported.
Results: A total of 248 and 167 pts were treated in the PDS 100 mg/mL Q24W and RBZ 0.5 mg Q4W (RBZ Q4W) arms, respectively; retention rate of 98.3% through W40. At BL, pts had a mean BCVA of 74.8 letters (20/32 Snellen) and a mean of 5.0 prior anti-VEGF injections. Change in BCVA score from BL averaged over W36 and W40 (95% CI) was +0.2 (-0.7, +1.1) and +0.5 (-0.6, +1.6) letters in the PDS and RBZ Q4W arms, respectively. With a difference (95% CI) of -0.3 (-1.7, +1.1) between arms, PDS was both noninferior and equivalent to RBZ Q4W. Change from BL in center point thickness at W36 was +5.4 µm (PDS) versus +2.6 µm (RBZ Q4W). 98.4% of PDS pts did not receive supplemental RBZ treatment during the first refill-exchange interval. The mean total number of RBZ treatments through W40 was 2.0 (PDS) versus 10.7 (RBZ Q4W). PDS implant insertion and refill exchange procedures were generally well tolerated. Systemic safety findings were comparable across arms.
Conclusions: The PDS phase 3 Archway trial met its primary endpoint and demonstrated that PDS 100 mg/mL Q24W treatment resulted in vision outcomes at W36/W40 that were equivalent to RBZ 0.5 mg Q4W injections with ~5-times fewer treatments. The PDS was generally well tolerated with a favorable benefit-risk profile.