OSLI Retina

February 2017

Issue link: http://osliretina.healio.com/i/783801

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100 Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina Practical Retina Incorporating current trials and technology into clinical practice An Overview of the Fovista and Rinucumab Trials and the Fate of Anti-PDGF Medications by Evan N. Dunn, MD; Veeral S. Sheth, MD The vitreoretinal community will re- member 2016 as the year that unfa- vorable anti–platelet-derived growth factor (anti-PDGF) clinical trial results ended the devel- opment of Fovista (pegpleranib; Oph- thotech, New York, NY) and Rinucum- ab (Regeneron, Tar- rytown, NY). The failure of these tri- als reaffirmed how important the in- novations made in 2006 with anti-vascular endothelial growth factor (anti-VEGF) were to our field and our patients. Evan N. Dunn, MD, and Veeral S. Sheth, MD, were tasked with ana- lyzing and dissecting the anti-PDGF clinical trials — beginning with the basic science behind anti-PDGF. They will also review novel, multitarget approaches to our diseases, as well as unique routes of delivery such as topical and suprachoroidal adminis- tration. Reading this article leads one to appreciate how high the anti-VEGF class of molecules has set the bar for the treatment of vitreoretinal dis- ease. Although recent clinical trial results have been a disappointment to our community (and our patients), we should be reassured by the fact that many development programs are strongly underway investigating novel approaches to treat back-of-the- eye disorders. Drs. Dunn and Sheth's insights will be highly valued by our community. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have remained the standard of care for neovascular age- related macular degeneration (AMD) since the landmark ANCHOR and MARINA studies published in 2006, which demonstrated the superiority of ranibizumab (Lucentis; Genentech, South San Francisco, CA) over photodynamic or sham therapy, respectively. 1,2 Since then, trials such as VIEW 1 and VIEW 2 have brought us new anti-VEGF agents such as aflibercept (Eylea; Regeneron, Tarrytown, NY). 3 Other trials, such as CATT and TREX-AMD, have demonstrated the effects of alternate dosing and, ultimately, the superiority of monthly ranibizumab and bevacizumab (Avastin; Genentech, South San Francisco, CA) dosing over less-frequent dosing intervals. 4,5 Studies such as HORIZON have demonstrated that switching from monthly dosing to less- frequent, investigator-determined, as-needed dosing resulted in disease destabilization, with 19.6% of patients initially treated with anti-VEGF in ANCHOR or MARINA losing 15 letters or more. 6 Even with monthly dosing, VIEW 1 and VIEW 2 demonstrated that fewer than 46% of patients achieved 20/40 or better vision whether they were treated with ranibizumab or aflibercept. 3 There are a handful of conclusions that can be made dur- ing this decade of innovation. First, anti-VEGF therapies have changed the landscape of ophthalmology and our ability to im- pact our patient's lives in a meaningful way. Second, despite this leap forward in quality of care, there have been no new-in-class medications since the advent of anti-VEGFs. Third, although a very large unmet need was filled with the anti-VEGFs, serious gaps still exist in our ability to manage patients with neovascu- lar AMD. These gaps include the existence of patients subop- Evan N. Dunn Veeral S. Sheth doi: 10.3928/23258160-20170130-02 Seenu M. Hariprasad Practical Retina Co-Editor

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