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BLOG: Still much progress ahead in retina
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When I was a resident, there was a joke that a retina specialist would do a refraction by turning the lights on and off in the room and asking, “Better one, or better two?” We refractive surgeons used to kid our retina colleagues by saying, “It takes no guts to operate on a blind eye.”
Indeed, the outlook for most patients with wet age-related macular degeneration and diabetic macular edema — two of the most common causes of legal blindness — was dismal. Treatment for both involved ablating tissue in the macula with laser. We knew the treatments were primitive, but we had little choice. Today, treatment of wet AMD and DME includes multiple options. Steroids, Macugen (pegaptanib, Bausch + Lomb), Avastin (bevacizumab, Genentech), Lucentis (ranibizumab, Genentech) and Eylea (aflibercept, Regeneron) have all but replaced laser treatment. All of these treatments basically target vascular endothelial growth factor.
All too often, when one anti-VEGF treatment fails, they all fail. Sometimes, even treatment “successes” lead to disappointing results. The Comparison of AMD Treatments Trials showed that, when treating AMD with either Avastin or Lucentis, only about 50% of patients achieved vision of 20/40 or better, no matter what treatment was used. For DME, the Protocol I study examined Lucentis, Eylea and Avastin. Again, in 1- and 3-year data, only about half of patients were restored to functional vision.
Compared with the days of laser ablating everything, these results are huge advances, but our patients do deserve more. They now want and expect results almost like we see in cataract surgery — consistent restoration of functional vision so they can read, drive and work again.
Attempts to find new drugs have been met with some successes and some notable failures. Recently, Regeneron developed a new AMD drug aimed at platelet-derived growth factor, a novel signal for AMD disease development. It failed in a phase 2 trial in which a combination with Eylea was compared with Eylea alone. More recently, Ophthotech announced in December the failure of a phase 3 trial in which its Fovista anti-PDGF drug failed in combination with Lucentis.
One promising approach is being taken by Allegro Ophthalmics, targeting the integrin receptors on the surface of vascular endothelial cells. These integrin receptors are thought to be critical in dictating cellular behavior, such as leaking fluid in DME and creating new vessels in AMD and proliferative diabetic retinopathy. Recent phase 2 studies in DME have shown monotherapy with Luminate, Allegro’s anti-integrin drug, to be non-inferior to anti-VEGF therapy with half the number of injections. Evidence suggests similar optimistic results may be seen in wet AMD.
What’s most promising is this drug targets a different mechanism of action for DME and AMD treatment, so it may succeed where anti-VEGF therapies fail. That’s great news for retina specialists, who need more options. Phase 2 results for a combination and sequential therapy study with Luminate and anti-VEGF therapy will be published later this year. While ongoing trials are necessary, this is one of the brightest spots in retina research.
Clearly there are no easy solutions to the problems of AMD and DME, but the next few years hold great promise for new therapies to treat AMD and DME more like cataracts, giving our growing aging population the promise for functional vision for a better life.
Disclosure: Hovanesian reports he has a small equity interest in Allegro Ophthalmics.