Demonstrating noninferior visual outcomes to traditional monthly intravitreal injections while reducing the need for office visits and repeat injections, the ranibizumab Port Delivery System (PDS) may offer an attractive treatment alternative for patients with neovascular AMD (nAMD).
Study Design
This was a Phase 3, open label, randomized, masked, noninferiority trial assessing the ranibizumab Port Delivery System (PDS) for nAMD in comparison to traditional monthly anti-VEGF injections. Patients accepted into this trial (n = 418) had been diagnosed with nAMD within 9 months of screening and were previously treated with (and responsive to) anti-VEGF therapy. Two hundred forty-eight patients randomized to the PDS arm received 100 mg/ml ranibizumab every 24 weeks; the remaining patients were treated every 4 weeks with 0.5 mg intravitreal ranibizumab injections. The primary end point was change in BCVA averaged across weeks 36 and 40 in comparison to baseline.
Outcomes
The adjusted mean change in BCVA was +0.2 letters in the PDS arm and +0.5 letters in the monthly treatment arm, a nonsignificant difference. This result met the primary objective, demonstrating that PDS is noninferior to monthly ranibizumab for improving BCVA. Additionally, 98.4% of patients in the PDS arm did not require supplemental ranibizumab treatment before the first refill-exchange at week 24.
Limitations
This study only included patients who were diagnosed with nAMD within 9 months of screening, so further studies are needed to evaluate the outcomes in patients with long-term disease or those who have received years of anti-VEGF therapy. Additionally, this was a US-based clinical trial with mostly White patients. Further studies are needed to validate treatment effectiveness and equivalency among global, ethnically diverse populations.
Clinical Significance
The need to lessen the treatment burden in patients with nAMD is well established. This study demonstrates that the ranibizumab PDS system is effective in increasing treatment durability for nAMD while maintaining clinically equivalent visual acuity gains to the gold standard monthly treatment regimen. The PDS automated delivery system has potential for improving patient compliance with treatment recommendations, since fewer in-office visits would be required with the PDS than with monthly injections. However, the PDS was voluntarily removed from the market due to cases of septum dislodgement, which caused the device to no longer function properly. The device is being redesigned, with plans for additional studies in development.
Financial Disclosures: Dr. Courtney Crawford discloses financial relationships with Genentech, Regeneron Pharmaceuticals (Consultant/Advisor, Lecture Fees/Speakers Bureau); Alcon Laboratories, Allergan, DORC International (Dutch Ophthalmic), Ocular Therapeutix, Oculus Surgical (Consultant/Advisor); Apellis, Iveric Bio (Lecture Fees/Speakers Bureau); Intelligent Retinal Imaging Systems, Topcon Medical Systems, Welch Allyn (Independent Contractor).