Anti-VEGF treatment of exudative age-related macular degeneration has represented a paradigm shift in the medical management of the disease however, not all patients obtain the same benefit and the burden of potentially monthly injections and ophthalmic visits can often reduce the effectiveness of the treatment. In an effort to overcome some of these challenges, a sustained release device that could be implanted in the eye and relied upon to deliver the required dosage without regular injections has been a long-held goal for industry and clinicians alike. In July, that goal got closer with the announcement of Phase II clinical results on the use of a small refillable ocular implant permitting patients with wet AMD to go several months without needing to visit the clinic for treatment.
Clinical research conducted to demonstrate the safety and efficacy of the device, no larger than a single grain of rice, involved the establishment of a multi-center, randomized, interventional, active treatment-controlled study. Termed “LADDER” (Long Acting DElivery of Ranibizumab; NCT02510794) the Phase II trial enrolled 243 patients with wet AMD across 50 clinical sites in the United States, patients who had previously responded to treatment with anti-VEGF therapy. The primary outcome of the trial was to determine the time until a patient first required a refill of the implant for three different concentrations of ranibizumab, compared to monthly intravitreal injections of ranibizumab 0.5 mg.
The trial, sponsored by Genentech in the US, used a “Port Delivery System” (the implant) with ranibizumab comprising one of three concentrations of ranibizumab: 10 mg/mL, 40 mg/mL or 100 mg/mL. Fifty-nine (59) patients received the 100 mg/mL dose from which an estimated 80% did not require a drug refill for up to 6 months or longer, while one-hundred and twenty (120) patients received the 40 mg/mL (n=62) or the 10 mg/mL (n=58) dosage, of which 71% and 63% respectively, were additionally capable of lasting six months or longer before their first drug refill. All groups were compared to a control cohort of patients receiving monthly intravitreal ranibizumab 0.5 mg injections and, according to the sponsor, patients in the 100 mg/mL arm achieved similar BCVA gains, and similar central retina thickness reductions when compared to monthly ranibizumab 0.5 mg injections. Commenting on the encouraging results, Dr. Carl Awh, MD, from Tennessee Retina in Nashville, stated, “to be able to offer our patients the outcomes achieved with monthly injections, but with a device that eliminates the need for those monthly injections, is very exciting.”