Fovista is an anti-platelet derived growth factor (PDGF) agent for wet age-related macular degeneration (AMD) combination therapy currently in phase 3 studies. Pending regulatory approval, Ophthotech will commercialize Fovista in the U.S., and has partnered with Novartis outside the U.S. in a deal worth more than $1 billion in upfront and potential milestone payments. The company currently has about $425 million in cash reserves to fund further studies.
The company’s phase IIb superiority trail is “the largest phase IIb ever done in wet AMD,” Dr. Guyer said. Fovista demonstrated a statistically significant superiority in this 449-patient randomized controlled trial with a 62% comparative benefit from baseline over ranibizumab monotherapy with no imbalances in the safety profile.
The company’s phase III program comprises three trials—two in combination with ranibizumab and one that combines Fovista with bevacizumab and with aflibercept. Results from the first two studies are expected in 4Q2016; the last study is currently enrolling patients. The “initial thoughts” are to file an NDA with data from the first two phase III studies only.
Phase IIb data showed an early and sustained improvement over time with maximum divergence at the last endpoint at 6 months. There were no imbalances in the safety profile, either in the eye or systemically between the various groups.
Fibrotic scarring “is the best biomarker for predicting poor visual acuity in patients,” Dr. Guyer said, and Fovista has been shown to be an antifibrotic agent. The phase IIb data found 27% of eyes treated with Fovista and ranibizumab versus 54% of those on ranibizumab monotherapy had a greater than or equal to two-step worsening of fibrosis.
Ophthotech is also looking to develop Fovista for the treatment of patients who have failed anti-vascular endothelial growth factor (VEGF) injections. An investigator sponsored trial enrolled eyes with an average 25 previous anti-VEGF injections with either persistent or recurrent fluid. There were two different treatment regimens of Fovista, a pre-treatment arm of Fovista followed by Fovista and then anti-VEGF treatment, 16.5 letter gain was seen in these treatment failure arms and in the arm that was given sequentially, 4.4 letters.
Finally, the company is evaluating the anti-VEGF small molecule tivozanib for the maintenance phase of wet AMD and in diabetic macular edema. The company plans to start a phase II/III of C5 complement inhibitor agent Zimura for the treatment of geographic atrophy.
David Guyer, MD
Under Dr. Guyer’s leadership, Ophthotech raised more than $350 million in financing from May to September 2013, including a $192 million IPO, a multi-tranched $125 million royalty financing deal with Novo A/S and a $50 million Series C private funding round.