Investigational wet AMD therapies aim for innovative targets
Many investigational drugs under development for the treatment of neovascular age-related macular degeneration (nvAMD) have advanced into the clinical trial stage, including several that are being evaluated in pivotal trials, said Peter K. Kaiser, MD.
Discussing the pharmaceutical pipeline, Dr. Kaiser provided a broad overview based on mechanism of action.
Highlighting agents that target vascular endothelial growth factor (VEGF) in the extracellular space, he said there are modalities that block VEGF-A. This group includes abicipar pegol (Allergan), a pegylated-designated Ankyrin repeat protein (DARPin); and brolucizumab (Alcon Laboratories), a single-chain, antibody fragment inhibitor of VEGF-A.
Both abicipar pegol and brolucizumab are in phase III study. In addition, OPT-302 (Ophthea), a trap molecule that blocks VEGF-C and VEGF-D, is being study in a phase I trial.
“OPT-302 is being investigated in combination with a VEGF-A blocker with the hope of achieving better blockade of the extracellular VEGF levels,” explained Dr. Kaiser, professor of ophthalmology, Cole Eye Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH.
He also noted that the patents for ranibizumab and bevacizumab (Avastin, Genentech), which also block VEGF-A, expire in the United States in 2019, and three companies are developing a ranibizumab biosimilar agent.
Other drugs in clinical development for nvAMD block platelet-derived growth factor (PDGF), with the aim of blocking pericyte recruitment to neovascular vessels. Investigational agents acting on PDGF include E10030 (Fovista, Ophthotech), MP0260/AGN-150998 (Allergan), and OHR-102 (squalamine, Ohr Pharmaceuticals).
E10030 blocks PDGF-BB. It failed in a phase III study in combination with bevacizumab or aflibercept (Eylea, Regeneron Pharmaceuticals). MP0260/AGN-150998 is a bispecific DARPin that blocks both PDGF-BB and VEGF.
OHR-102 is being developed as a topical drop. It is a calmodulin inhibitor that prevents growth factor receptor activation and interferes with the activity of PDGF, as well as VEGF and basic fibroblast growth factor. It is also being investigated in a phase III trial.
Drugs in development for nvAMD also include several that act as tyrosine kinase inhibitors—DE-120 (Santen), PAN-90806 (Panoptica), and OTX-IVT (Ocular Therapeutix). Results reported in October, 2016, from a phase I/II trial with topical PAN-90806 showed promising biological efficacy. The other agents are in phase II trials.