Positive Phase II results for the first-ever eye implant to achieve sustained delivery of a biologic medicine, Lucentis, to treat people with wet age-related macular degeneration. Genentech/Roche + Novartis

Genentech, a member of the Roche Group announced positive, top line results from the Phase II LADDER study evaluating the efficacy and safety of its investigational Port Delivery System with ranibizumab (PDS) in people with wet age-related macular degeneration (AMD), a leading cause of blindness for people age 60 and over, in the United States.

The majority of PDS patients enrolled in the LADDER trial went six months or longer between implant of the device and the first, required refill. Vision outcomes in the high-dose PDS group were similar to monthly ranibizumab eye injections and were maintained throughout the study period. These data were presented by Carl C. Awh, M.D., of Tennessee Retina in Nashville, TN, at the 36th Annual Meeting of the American Society of Retina Specialists (ASRS) in Vancouver, British Columbia, Canada.

The current standard of care for wet AMD can be burdensome because it requires patients to visit their ophthalmologist as often as monthly for eye injections of anti-vascular endothelial growth factor (VEGF) therapy to help maintain vision gains and/or prevent vision loss. This high treatment burden with anti-VEGF therapy can lead to under-treatment of wet AMD and, potentially, less than optimal vision outcomes.

LADDER study patients implanted with the PDS received one of three concentrations of ranibizumab: 10 mg/mL, 40 mg/mL or 100 mg/mL. For PDS patients receiving the 100 mg/mL dose (n=59), approximately 80 percent were able to go six months or longer until their first refill was required. Of the PDS patients receiving the 40 mg/mL (n=62) or the 10 mg/mL (n=58), 71.3 percent and 63.5 percent respectively, were able to go six months or longer before their first refill. Secondary endpoints of the study included assessments of vision and anatomic outcomes when compared to monthly intravitreal ranibizumab 0.5 mg injections. Patients in the PDS 100 mg/mL arm achieved similar gains in Best Corrected Visual Acuity (BCVA) and similar reductions in central retina thickness compared to patients receiving monthly ranibizumab 0.5 mg injections. The PDS is implanted during a surgical procedure. It is refilled using a customized needle in a minimally invasive office-based procedure. The results from this study will help determine the most appropriate dose and fixed treatment interval to study in the Phase III program to sustain optimal vision outcomes in clinical practice for patients with wet AMD.

Additional data analyses of the LADDER study are on-going and will be presented at future medical meetings. The PDS Phase III clinical development program is expected to begin later in 2018.

Comment: The small, refillable eye implant, which is slightly longer than a grain of rice, is designed to allow people with wet AMD to go several months without needing to visit their ophthalmologist for treatment.