After the initial 9-month period of the phase 2 Ladder study, which compared use of the use of the Port Delivery System (PDS) and monthly intravitreal injections of ranibizumab in patients with neovascular AMD, patients were allowed to enroll in the long-term extension phase. The end-of-study results have now been reported.
Study design
This article reports the end-of-study results for the extension phase of the multicenter, randomized, active treatment-controlled phase 2 Ladder trial. A total of 220 patients aged ≥50 years with neovascular AMD were randomized 3:3:3:2 to receive 1 of 3 dosing regimens of ranibizumab administered with the PDS (10, 40, or 100 mg/mL ) or monthly ranibizumab 0.5-mg intravitreal injections. The primary efficacy endpoint was the time from PDS insertion to the first meeting of protocol-defined refill criteria; efficacy outcomes assessed at the end of the study included changes in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) from baseline.
Outcomes
Those patients assigned to the PDS arms were in the study for a mean time of 22.1 months. The median time to first refill was 8.7 months for the 10-mg/mL group, 13.0 months for the 40-mg/mL group, and 15.8 months for the 100-mg/mL group. Greater gains in BCVA from baseline to month 22 were seen in patients in the PDS 100-mg/mL arm (+2.9 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) than in the patients in the PDS 10-mg/mL or 40 mg-mL arms (–4.6 ETDRS letters and ‒2.3 ETDRS letters, respectively), and improved gains were comparable to those seen in patients in the monthly ranibizumab arm (+2.7 ETDRS letters). Patients in the PDS 100-mg/mL group and patients in the monthly ranibizumab injection group also had comparable efficacy in terms of changes in mean CFT from baseline.
Limitations
The range of time that patients were studied was large and variable, from 11 months to 37.6 months. This led to some limitations in analysis around the longer-term timepoints.
Clinical significance
The idea of a long-acting treatment for AMD is exciting, as it will decrease the treatment burden for both patients and physicians. Assuming that the results from the currently ongoing phase 3 trial will confirm these outcomes, physicians have many points to consider when thinking about adopting this treatment paradigm. First, patients in this older population may be less comfortable with surgery and less medically stable. Second, these patients will need to be willing to accept the surgical risks in order to decrease the number of visits. These risks include but are not limited to endophthalmitis, vitreous hemorrhage, retinal detachment, and dislodging of the implant. Third, many retina physicians have built their practices on efficient injection throughput, and some do not perform surgeries. With that in mind, decreased patient volumes will likely lead to decreased overall reimbursement. If that is the case, it's unclear how or whether this new procedure will be adopted by the retina community.