Roche Begins Phase 3 for Sustained-Release Ranibizumab

Following the successful phase 2 LADDER trial for the delivery of a special formulation of ranibizumab via a refillable, sustained-release implant called the Port Delivery System (PDS), Roche/Genentech has begun the 360-patient ARCHWAY trial with refills scheduled every 24 weeks. The primary endpoint will be change in BCVA from baseline to the average BCVA of weeks 36 and 40.

The 96-week phase 3 study is a randomized, multicenter, open-label (visual assessor-masked), active-comparator study designed to assess the efficacy, safety, and pharmacokinetics of 100mg/ml delivered via the PDS, compared with monthly ranibizumab intravitreal injections at 0.5 mg (10 mg/mL) in participants with wet AMD. Participants must be previous responders to anti-VEGF therapy.

In the 243-patient LADDER trial, study patients implanted with the PDS were all responders to previous anti-VEGF treatment. They were randomized to monthly intravitreal injections of ranibizumab or to treatment using the PDS filled with 1 of 3 different concentrations of ranibizumab. For PDS patients receiving the 100 mg/mL dose (n=59), approximately 80% were able to go 6 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% and 63.5%, respectively, were able to go 6 months or longer before their first required refill.

Adverse events encountered during LADDER included postoperative vitreous hemorrhages in the initial months of study enrollment, which were minimized by modifying the procedure to include laser coagulation of the choroid before incision. This step helped reduce the vitreous hemorrhage rate to about 5%. Most vitreous hemorrhages were mild and all cases were manageable. A very small number of the implant reservoirs were explanted during the trial. Some cases of conjunctival erosion were reported, but Roche/Genentech believes that an additional modification to the surgical technique can minimize that risk.

Regeneron, which developed Eylea (aflibercept), the only other FDA-approved anti-VEGF for retinal disease, also has a sustained-release initiative under way with partner Ocular Therapeutix.