SAN FRANCISCO — A port delivery system device with ranibizumab was effective, well tolerated and required infrequent refills in patients with neovascular age-related macular degeneration, according to final end-of-study results of the LADDER phase 2 trial.
The study examined the durability, efficacy and safety of the surgically implanted PDS device (Genentech) compared to the gold standard of monthly intravitreal injections of ranibizumab over a mean of 22 months, Carl Regillo, MD, said at Retina Subspecialty Day at the American Academy of Ophthalmology annual meeting.
A total of 220 patients with neovascular AMD were randomized 3:3:3:2 to receive 10 mg/mL, 40 mg/mL or 100 mg/mL of ranibizumab via the PDS device or 0.5 mg via monthly intravitreal injections.
The primary endpoint was time to first PDS refill. Safety and change from baseline in best corrected visual acuity (BCVA) and central foveal thickness (CFT) were also assessed. Patients who demonstrated increases in CFT, decreases in BCVA or new macular hemorrhage required a refill.
The median time to first refill was 15.8 months in the highest concentration arm, 13 months in the medium concentration arm and 8.7 months in the lowest concentration arm. The high dose of ranibizumab performed best, according to Regillo, with about 60% of patients going at least 12 months without requiring a refill. In the 31 of 59 patients (52.5%) who did require a refill, median time to both the first and second refills was 8.8 months.
BVCA and CFT outcomes were comparable between the high dose arm and the monthly injection arm, he said.
Regarding safety, Regillo said that the high rate of vitreous hemorrhage reported in the primary analysis of the trial has been greatly reduced.
“The surgical technique was modified, and that hemorrhage rate went way down, averaging about 4% thereafter through the remainder of the study, and big hemorrhages were very rare,” Regillo said.
Other notable PDS-associated adverse events, such as conjunctival issues, infection and retinal detachment, were “essentially unchanged” compared with the primary analysis, averaging around 1% to 2%, Regillo said.
The final findings of the LADDER trial support the phase 3 Archway 24-week study design, which is fully enrolled with results pending in 2021, Regillo said. – by Alaina Tedesco
Reference: Regillo C. Port delivery system with ranibizumab for neovascular AMD: LADDER phase 2 trial end of study results. Presented at: American Academy of Ophthalmology annual meeting; Oct. 11-15, 2019; San Francisco.
Disclosure: Regillo reports he is a consultant for Genentech.