A refillable ranibizumab implant may soon allow patients with wet AMD to go 6 months or longer between visits, according to Carl D. Regillo, MD, who presented topline results from the LADDER trial during Retina Subspecialty Day on Friday.
The port delivery system (PDS) is designed to continuously release a special formulation of ranibizumab over time through passive diffusion. Implantation calls for a short surgical procedure in the operating room, which requires no sutures aside from those required to close the conjunctiva. Refills, on the other hand, are accomplished with a simple in-office procedure using a customized needle.
LADDER trial design. The phase 2 Long-Acting Delivery of Ranibizumab (LADDER) trial was a 4-arm trial that enrolled 220 patients who had previously shown good response to anti-VEGF therapy. Each participant was randomized to 1 of 3 PDS doses (10, 40, or 100 mg/mL) or monthly intravitreal ranibizumab injections (0.5 mg). The primary endpoint was time to the first refill, which was based on prespecified anatomic and vision criteria.
High-dose arm shows promise. Ultimately, the high-dose PDS arm (100 mg/mL) showed the best response. Within that arm, the median time to refill was 15 months, and approximately 80% of implants were able to go more than 6 months without needing their first refill. The median time to refill was 13 months in the 40 mg/mL arm, and 8.7 months in the 10 mg/mL arm. The high-dose PDS arm showed substantial vision gains through 18 months of follow-up. These gains were comparable to those seen in the monthly injection arm.
Safety first. Early on, investigators noted that half of the PDS participants developed vitreous hemorrhage. The trial was halted and some adjustments were made to the surgical procedure. Following the modifications, the rate of vitreous hemorrhage dropped to approximately 5%. The surgery and refill procedure were well tolerated, and there were no differences in systemic safety concerns across all arms.
Dr. Regillo concluded that the PDS holds promise for minimizing the high treatment burden associated with monthly intravitreal injections—for both patients and physicians. A phase 3 clinical trial is currently underway.—Keng Jin Lee
Financial disclosures: Acucela: S; Aerpio: C; Alcon Laboratories, Inc.: C,S; Allergan: C,S; Bausch+Lomb: C; Bayer Healthcare Pharmaceuticals: C; Genentech: C,S; GlaxoSmithKline: S; Notal Vision, Inc.: C,S; Novartis Pharmaceuticals Corporation: C,S; Regeneron Pharmaceuticals, Inc.: C,S; ThromboGenics, Inc.: S.
Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.
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