Retina Today - A Novel Sustained-release Intravitreal Drug Delivery System for Retinal Vascular Disease (April 2010)

摘要

The past decade has seen the introduction of numerous pharmacologic treatments for retinal diseases. The prime example of this was seen with therapies for choroidal neovascularization secondary to age-related macular degeneration (AMD); first, photodynamic therapy with or without intravitreal triamcinolone,1 followed shortly by intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors,2-4 improved the prognosis for patients with this heretofore blinding degenerative condition. Now AMD patients may reasonably hope to maintain and even improve visual acuity. This improvement in outcomes has come at a cost, however, as patients, retina specialists, and health care systems are challenged with managing frequent visits and potential risks of repeated intravitreal injections. Retinal vein occlusion (RVO), one of the most common retinal vascular disorders, second in prevalence only to diabetic retinopathy, may be the next disease to be affected by the retina pharmacologic revolution. Clinical trials of an anti-VEGF agent for treatment of central and branch RVO have shown clinically and statistically significant improvements in visual acuity.5,6 Again, however, there is the potential for the same treatment burden as with AMD: The improved vision results in the trial were achieved with monthly intravitreal injections. Considering this current trend, it is clear that a sustained- release drug delivery method for treatment of retinal diseases is an unmet clinical need. An injectable, biodegradable, sustained-release system could reduce the treatment burden for patients and physicians. To answer this need, Icon Biosciences, Inc. (Sunnyvale, CA) is developing a promising drug delivery technology called Verisome, a delivery system that can be injected into the vitreous as a liquid via a standard 30-gauge needle. When the Verisome-based product is injected into the vitreous, it coalesces into a single spherule that settles in the inferior vitreous. The biodegradable vehicle provides controlled, extended drug release; the shrinkage of the Verisome spherule over time reflects the simultaneous degradation of the delivery system and release of drug. This article presents some of the science behind this delivery system and summarizes results of a recent clinical trial. THE SCIENCEThe Verisome technology is a robust drug-delivery system that, according to its manufacturer, can potentially be used to release a broad range of pharmaceutical agents, including small molecules, peptides, proteins, and monoclonal antibodies. The basic technology is highly versatile and can be formulated into numerous products, as a biodegradable solid, gel, or liquid that can provide drug release in a controlled manner over weeks to a year for ocular, systemic, or topical applications. 7 Ophthalmic applications are focused on its ability to create an injectable liquid or slightly viscous gel. The drug delivery system degrades as the active agent is released over the intended time duration. In ophthalmology, this mode of delivery offers clinical advantages because the physician can easily assess the status of therapy by observing the drug-containing system in place in the eye. When the spherule is no longer visible, all the drug has been released, and no vehicle remains in the eye. The ability to observe the druga??s progress facilitates planning for additional dosing. In the future, the flexibility of the system, along with this ability to observe its status directly, may allow physicians to tailor the duration of drug delivery to individual patients, potentially leading to cost efficiencies and better clinical results. Rather than having therapy dictated by the design of the delivery vehicle, physicians may be able to administer drugs with what they deem to be the appropriate duration and intensity of treatment for each patient. For its first clinical trial, the Verisome