Abstract
Two generations ago, two therapeutic advances were made in ophthalmic drug delivery for the treatment of glaucoma – a prodrug (Propine® (dipivefrin), and a cul-de-sac sustained-release insert (Ocusert®, pilocarpine). A generation later, patients with sight-threatening posterior segment infection or inflammation were able to be treated with an intravitreal implant (Vitrasert® (ganciclovir) and Retisert® (fluocinolone acetonide). More recently, an erodible implant has been approved for several posterior segment indications (Ozurdex® (dexamethasone). Additional systems are in development for both zero-order and pulsatile delivery of therapeutic agents to the eye. 1
In this issue, Associate Editor Uday B. Kompella, PhD has put together nearly a score of articles focusing on nanotechnology and drug delivery. These articles range from state-of-the-art reviews of issues in ophthalmic drug delivery to practical cases of use of 21st century drug delivery and nanotechnology. The path from research to development to market is long, tortuous, expensive and risky. However, we hope that the active areas of research presented in this issue will result in improved efficacy, safety, and duration – in summary – improved therapeutics for patients with ophthalmic disease.
In this recent period there are two developments in the area of drug delivery – EyeGate Pharma completed enrollment in a study of their iontophoresis technology, and Icon Bioscience obtained Orphan Drug Designation for an intraocular delivery system. Other ocular pharmaceutical activities includes firms announcing efforts to treat retinal degeneration, glaucoma, retinoblastoma and Graves' Orbitopathy; early stage trials for the treatment of dry eye and scleritis, and development of more advanced treatments for uveitis and macular edema due to central retinal vein occlusion, as well as regulatory/formulary activity on a treatment for diabetic macular edema.
Ophthalmic Pharmaceuticals
• Eleven Biotherapeutics has initiated a Phase 1b clinical trial to evaluate EBI-005, its lead ophthalmic protein product that inhibits the interleukin-1 (IL-1) receptor, in patients with dry eye disease (December 2012).
• EyeGate Pharma completed enrollment in a pivotal Phase III study of EGP-437 (dexamethasone) in patients with anterior uveitis (December 2012).
• Icon Bioscience, Inc. announced that melphalan intraocular injection for the treatment of retinoblastoma has been granted Orphan Drug Designation by the U.S. Food & Drug Administration (January 2013).
• Neuron Systems, Inc., developing treatments for the dry form of age-related macular degeneration, is now known as Aldexa Therapeutics, Inc. (January 2013).
• QLT, Inc. has entered into an agreement with Mati Therapeutics, Inc. to acquire the assets related to QLT's punctal plug drug delivery system technology (December 2012).
• Regeneron Pharmaceuticals, Inc., and Bayer HealthCare announced submission of an application for marketing authorization in Europe for Eylea® (aflibercept) Injection for the treatment of macular edema after central retinal vein occlusion (December 2012).
• Rigel Pharmaceuticals, Inc. initiated a Phase 1 clinical study of R348, a topical JAK/SYK inhibitor, as a potential therapeutic for chronic dry eye (December 2012).
• River Vision Development Corp. is developing a novel protein therapy, RV 001, for the treatment of Graves' orbitopathy (December 2012).
• Sucampo Pharmaceuticals, Inc. received an approval of an supplemental New Drug Application for RESCULA® (unoprostone isopropyl ophthalmic solution) 0.15% for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension from the U.S. Food and Drug Administration (FDA). The supplement states a possible effect on the BK (Big Potassium) channels and ClC-2 chloride channels, but the exact mechanism is unknown at this time (December 2012).
• XOMA Corporation has selected the active noninfectious anterior scleritis as the third indication in a proof-of-concept program for gevokizumab, a systemically administered anti-IL-1β-neutralizing antibody (December 2012).
Regulatory, Government, and Pharmaceutical Industry
• Lucentis® (ranibizumab) was recommended for impaired sight in some patients with diabetic macular edema by the U.K. National Institute for Health and Clinical Excellence (NICE). This decision, which reverses a previous decision, is partially based upon a reduction in price by the manufacturer (January 2013).
Footnotes
Author Disclosure Statement
The author consults for numerous ophthalmic pharmaceutical and medical device firms.