Genentech is again pursuing novel and creative ways to improve patient outcomes by testing long-term anti-VEGF delivery in the LADDER trial (Study of the Efficacy and Safety of the Ranibizumab Port Delivery System for Sustained Delivery of Ranibizumab in Participants With Subfoveal Neovascular Age-Related Macular Degeneration). This trial has the potential to dramatically change the nature of how we approach and manage neovascular AMD.
This Phase II clinical study compares three different formulations of ranibizumab delivered via the Ranibizumab Port Delivery System (RPDS) implant compared with injections of ranibizumab, in participants with neovascular AMD. If the program moves forward into a registration trial and eventually gains FDA approval, long-term anti-VEGF delivery will become a realistic option.
The device is another invention developed by our colleague Eugene De Juan, Jr. MD, Founder of the Menlo Park incubator ForSight Labs. De Juan, who dramatically changed the face of vitreoretinal surgery with the invention of sutureless small gauge vitrectomy, continues to innovate. The ForSight VISION4 PDS device is a durable intravitreal implant that is placed through a scleral incision in a one-time surgical procedure. A physician in an office setting then refills it using a proprietary refill needle.
Questions abound however. Will the device cause complications? Will sustained anti-VEGF delivery increase the rates of geographic atrophy and glaucoma? Is pulsatile dosing with intermittent injections the preferred pharmacodynamic approach? Will physicians and patients eventually choose a surgical procedure rather than an office based approach? How will treat and extend paradigms compare to steady state delivery?
With all technology, there are more questions than answers in early phase programs, and this one is no different. However, given the focus on intravitreal injection in our clinical practices, the LADDER trial has the potential of having a major impact on how we spend our days as retinal specialists… So we will all stay closely tuned to the data from this important trial.
Jonathan Prenner, M.D.