Issue link: http://retinalphysician.epubxp.com/i/783300
6 R E T I N A L P H Y S I C I A N . C O M | O C T O B E R 2 0 1 6 SUBSPECIALTY NEWS R E T I N A L P H Y S I C I A N | J A N U A R Y - F E B R U A R Y 2 0 1 7 6 n Long-anticipated initial data from two large phase 3 pivotal clinical trials that studied a combination of Ophthotech's proprietary anti-PDGF drug Fovista and Genentech's Lucentis (ranibizumab) for wet AMD showed that the combi- nation produced no significant benefit in visual acuity over Lucentis monotherapy at 12 months. A highly positive 449-patient phase 2b trial of the Ophthotech combo had led many in the retina community to believe that an anti-PDGF/anti-VEGF combination would usher in the next generation of more durable and effica- cious treatments for wet AMD. But the news hit stakeholders hard. On Wall Street, Ophthotech shares immediately fell from $38 to less than $6. And the company announced recently that it was eliminating at least 125 posi- tions, leaving just dozens behind. e future of some clinical trials also are affected. e rationale behind anti-PDGF/ anti-VEGF combinations is that the anti-PDGF agent has the ability to break down the barrier of pericytes that protect the VEGF, thus enabling the anti-VEGF agent to be more effective in eliminating the unwanted VEGF. Several companies have been active in this area of research, including Regeneron and Allergan. However, a Regeneron combination of its own pro- prietary anti-PDGF and its anti-VEGF Eylea has not shown a benefit in early data from a phase 2 clinical trial. David R. Guyer, MD, CEO of Ophthotech said the company was "dis- appointed" with the results and "would continue to analyze the data to better understand" what happened. Both Dr. Guyer and Ophthotech President Samir Patel, MD, are con- sidered pioneers in the development of retina drugs, having successfully shepherded the anti-VEGF aptamer Macugen through the FDA approval process when they were principals of Eyetech Corporation a decade ago. THE TRIALS e two clinical trials (OPH1002 and OPH1003) were international, mul- ticenter, randomized, double-masked, controlled phase 3 studies evaluating the safety and efficacy of 1.5 mg of Fovista administered in combination with Lucentis compared to Lucentis monotherapy. e trials enrolled an aggregate of 1,248 patients with wet AMD. e results from the trials' data- bases were unmasked and analyzed concurrently. e combined analysis showed that patients receiving Fovista combination therapy gained a mean of 10.24 let- ters of vision on the Early Treatment of Diabetic Retinopathy Study (ETDRS) standardized chart at 12 months, com- pared to a mean gain of 10.01 ETDRS letters for patients receiving Lucentis monotherapy,. In OPH1002, consisting of 619 treated patients, subjects receiving Fovista combination therapy gained a mean of 10.74 letters of vision on the ETDRS standardized chart at 12 months, com- pared to a mean gain of 9.82 ETDRS letters in patients receiving Lucentis monotherapy, a resulting difference of 0.92 ETDRS letters. In OPH1003, con- sisting of 626 treated patients, subjects receiving Fovista combination therapy gained a mean of 9.91 letters of vision on the ETDRS standardized chart at 12 months, compared to a mean gain of 10.36 ETDRS letters in patients receiv- ing Lucentis monotherapy, a resulting difference of -0.44 ETDRS letters. In the phase 3 trials, the anti-PDGF and anti-VEGF drugs were adminis- tered 30 minutes apart. However, in a small investigator- sponsored trial, Pravin Dugel, MD, of Retinal Consultants of Arizona, admin- istered the anti-PDGF a day before he injected the anti-VEGF. is "pretreat- ment" protocol demonstrated encourag- ing results in a difficult-to-treat patient cohort, Dr. Dugel reported, and may possibly be an avenue to continue to pur- sue. Ophthotech has a third ongoing phase 3 trial in which combinations of Fovista and Eylea and Fovista and Avastin (Genentech) are being studied in com- parison to anti-VEGF Eylea or Avastin monotherapy. Ophthotech AMD Combo Fails in Phase 3 No significant benefit over Lucentis monotherapy. BY JERRY HELZNER, CONTRIBUTING EDITOR IN BRIEF n Santen uveitis drug effective in phase 3 Santen Pharmaceutical (Osaka, Japan) said topline data from its phase 3 SAKURA study dem- onstrated that its Opsiria therapy (sirolimus intravitreal injection) for noninfectious posterior uveitis met its objectives in combating inflammation as measured by vitreous haze. The company said it would file a New Drug Application with the FDA in early 2017.