Patients with neovascular agerelated macular degeneration treated with ranibizumab 100 mg/mL delivered via the port delivery system in a phase II study went a median of 15 months before needing a device refill. A phase III study is under way.
Reviewed by Carl D. Regillo, MD
Ranibizumab 100 mg/mL delivered via the port delivery system (PDS) (Genentech) holds promise for providing safe and effective durable control of neovascular age-related macular degeneration (nAMD) in patients with anti-VEGF responsive disease, according to results of the LADDER study.
The phase II clinical trial was designed to characterize the durability and safety of the device. The durability results were very promising and exceeded expectations, and the safety profile looked good, especially after introducing modifications to the surgical technique, said Carl D. Regillo, MD, study investigator, and chief of the Retina Service, Wills Eye Hospital, Philadelphia.
“The techniques for device implantation and refilling are unique, but with training and meticulous care, they can be readily and safely adopted by vitreoretinal surgeons,” Dr. Regillo added. In LADDER, 220 patients were randomly assigned 3:3:3:2 to treatment with PDS 10, 40, or 100 mg/mL or intravitreal ranibizumab 0.5 mg (Lucentis, Genentech). The PDS—a scleral-based intravitreal reservoir releasing ranibizumab via passive diffusion—was refilled as needed based on protocol-defined criteria for identifying disease activity. Patients in the ranibizumab group received monthly intravitreal injections.
Time until the first need for implant refill was analyzed as the primary end point. The results showed a clear dose response, with the interval being longest in the PDS 100 mg/mL group. Median time to first refill was 15 months in the PDS 100 mg/mL group, 13.0 months for the 40 mg/mL group, and 8.7 months in the PDS 10 mg/mL group.
Among patients in the PDS 100 mg/mL group, 93% had not yet met refill criteria at 3 months, 80% still did not need a refill at 6 months, and 69% went at least 9 months without a refill.
Functional and anatomic outcomes for patients receiving the PDS 100 mg/mL implant were comparable to those in the monthly ranibizumab group. Overall, the implant insertion surgery and refill procedures were well tolerated, and there were no meaningful differences between treatment arms in systemic safety, Dr. Regillo said.
Carl D. Regillo, MD
E: [email protected]
Dr. Regillo receives research grant support from and is a consultant to Genentech.