Eyeworld

EW RETINA 134 March 2015 by Lauren Lipuma EyeWorld Staff Writer Retina drugs on the market and in the pipeline Medical retina seeing new innovations I ntravitreal drugs on the market target the most common retinal diseases seen by specialists today: wet age-related macular degeneration (AMD), diabetic macular edema (DME), and reti- nal vein occlusion-related macular edema (RVO-ME). Retina specialists Carl Regillo, MD, FACS, director of the retina service, Wills Eye Hospi- tal, Philadelphia, and Pravin Dugel, MD, managing partner, Retinal Consultants of Arizona, Phoenix, and clinical professor, USC Eye Institute, Keck School of Medicine, Los Angeles, discussed information anterior segment surgeons should know regarding the indications and efficacy of current retina drugs and the treatment potential of new agents on the horizon. Anti-VEGF agents The most widely used class of intravitreal drugs, anti-VEGFs are the mainstay for treating AMD, DME, and RVO-ME, Dr. Regillo said. Ranibizumab (Lucentis, Genentech, South San Francisco), a monoclonal anti-VEGF antibody fragment, was approved by the Food and Drug Administration (FDA) in 2006, and aflibercept (Eylea, Regeneron Pharmaceuticals, Tarrytown, N.Y.), a recombinant fusion protein, came to market in the U.S. in 2011. Like Lucentis, Eylea was first approved for wet AMD, then RVO-ME, and most recently for DME. Bevacizum- ab (Avastin, Genentech), another monoclonal antibody made by Genentech, is a cheaper alternative to Lucentis, but not FDA approved for ophthalmic use. Corticosteroids Intravitreal steroids treat both types of macular edema and last longer than anti-VEGF agents, but they pro- duce the side effects of IOP elevation and cataract promotion, so they are generally considered a second-line treatment for those diseases, Dr. Regillo said. Bolus corticosteroid injection dates back to 2000, but more recent- ly, retina specialists have been using a sustained-release biodegradable dexamethasone implant, Ozurdex (Allergan, Irvine, Calif.). Ozurdex is approved for RVO-ME, uveitis, and most recently for DME. The implant is given in the same way as a normal intravitreal injection, but the injector is special- ly designed with a sensory feedback mechanism to inform the surgeon when the injector has released its implant, Dr. Dugel explained. As use of the implant has risen, bolus steroid injections have declined, he added. Vitreolytics In addition to AMD and macular edema, retina specialists commonly treat vitreomacular traction disor- ders. Ocriplasmin (Jetrea, Thrombo- Genics, Leuven, Belgium) is the first vitreolytic agent approved for this use in the United States. Approved by the FDA in 2012, ocriplasmin is a non-specific serine protease that causes vitreous liquefaction as well as vitreous separation. "This first-in- class enzyme molecule is injected intravitreally to promote vitreous separation from the macula," Dr. Regillo said. "It is used instead of surgery in select cases to treat vitreo- macular traction with or without macular holes." Agents on the horizon According to Dr. Dugel, the most promising new treatments in de- velopment are anti-PDGF therapies and smaller anti-VEGF products for treating AMD. The idea behind small anti- VEGF products is that they will have a stronger binding affinity, improved efficacy, and longer duration. "More importantly, they may be able to be packaged into a sustain- able drug delivery device, which would obviate the need for frequent injections, and may lead to a more sustainable treatment model," Dr. Dugel said. Alcon (Fort Worth, Texas) and Novartis (Basel, Switzerland) are jointly developing RTH258, a small, humanized anti-VEGF antibody fragment that inhibits all isoforms of VEGF-A. Allergan is developing an anti-VEGF DARPin (abicipar pegol), a small, engineered protein that mimics the action of an antibody with high specificity and binding affinity. DARPins are derived from natural adaptor proteins, ankyrins, which mediate the attachment of membrane-bound proteins to the cell cytoskeleton. The anti-PDGF agent Fovista (Ophthotech, New York) is being developed to work in combination with anti-VEGF agents to combat neovascularization. Anti-PDGFs bind and strip pericytes, cells that serve as an armor for neovascular mem- branes. Once the pericytes are gone, anti-VEGF can attack the naked en- dothelial cells, so the combination is particularly powerful, Dr. Dugel said. Fovista is currently in phase 3 clinical trials; its phase 2 trial, the largest ever done in retina, showed that the combination of Fovista and Lucentis had a 62% increase in efficacy from baseline over Lucentis treatment alone. Developments also continue in corticosteroid delivery. Alimera (Alpharetta, Ga.) and pSivida (Watertown, Mass.) have partnered to manufacture Iluvien, a non- biodegradable implant indicated for DME that elutes the steroid fluocinolone acetonide for up to 3 years. Surrounded by an inert coating, the implant elutes drug only from its ends, giving it the near zero-order kinetics that allow it to last for such a long time. Iluvien received FDA approval for the treat- ment of DME in the U.S. in Septem- ber 2014, and the drug is expected to be commercially available in the country soon. It is commercially available in the U.K. and Germa- ny and has received or is pending marketing approval in a number of other countries in Europe. It has the CE mark. "FDA approval of Iluvien, our third FDA-approved product for ret- inal disease, provides an important treatment option for DME patients in the U.S., the majority of whose DME, despite anti-VEGF intraocular injections as frequently as monthly, is not optimally managed," said Paul Ashton, PhD, president and chief executive officer of pSivida, in a press release. "Iluvien's clinical trials showed that Iluvien can actually reverse vision loss in many DME patients." EW Editors' note: Drs. Dugel and Regillo have financial interests with Alcon, Alimera, Allergan, Genentech, Novartis, Ophthotech, Regeneron Pharmaceuti- cals, and ThromboGenics. Contact information Regillo: cregillo@aol.com Dugel: pdugel@gmail.com Ozurdex applicator Source: Allergan

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