Pipeline therapies for neovascular age related macular degeneration

Abstract

Age related macular degeneration (AMD) is the most common cause of vision loss in the elderly population. Neovascular AMD comprises 10% of all cases and can lead to devastating visual loss due to choroidal neovascularization (CNV). There are various cytokine pathways involved in the formation and leakage from CNV. Prior treatments have included focal laser therapy, verteporfin (Visudyne, Bausch and Lomb, Rochester, New York) ocular photodynamic therapy, transpupillary thermotherapy, intravitreal steroids and surgical excision of choroidal neovascular membranes. Currently, the major therapies in AMD focus on the VEGF-A pathway, of which the most common are bevacizumab (Avastin; Genentech, San Francisco, California), ranibizumab (Lucentis; Genentech, South San Francisco, California), and aflibercept (Eylea; Regeneron, Tarrytown, New York). Anti-VEGF agents have revolutionized our treatment of wet AMD; however, real world studies have shown limited visual improvement in patients over time, largely due to the large treatment burden. Cheaper alternatives, including ranibizumab biosimilars, include razumab (Intas Pharmaceuticals Ltd., Ahmedabad, India), FYB 201 (Formycon AG, Munich, Germany and Bioeq Gmbh Holzkirchen, Germany), SB-11 (Samsung Bioepsis, Incheon, South Korea), xlucane (Xbrane Biopharma, Solna, Sweden), PF582 (Pfnex, San Diego, California), CHS3551 (Coherus BioSciences, Redwood City, California). Additionally, aflibercept biosimilars under development include FYB203 (Formycon AG, Munich, Germany and Bioeq Gmbh Holzkirchen, Germany), ALT-L9 (Alteogen, Deajeon, South Korea), MYL1710 (Momenta Pharamaceuticals, Cambridge, MA, and Mylan Pharmacueticals, Canonsburg, PA), CHS-2020 (Coherus BioSciences, Redwood City, California). Those in the pipeline of VEGF targets include abicipar pegol (Abicipar; Allergan, Coolock, Dublin), OPT-302 (Opthea; OPTHEA limited; Victoria, Melbourne), conbercept (Lumitin; Chengdu Kanghong Pharmaceutical Group, Chengdu, Sichuan), and KSI-301 (Kodiak Sciences, Palo Alto, CA). There are also combination medications, which target VEGF and PDGF, VEGF and tissue factor, VEGF and Tie-2, which this paper will also discuss in depth. Furthermore, long lasting depots, such as the ranibizumab port delivery system (PDS) (Genentech, San Francisco, CA), as well as others are under evaluation. Gene therapy present possible longer treatments options as well and are reviewed here. This paper will highlight the past approved medications as well as pipeline therapies for neovascular AMD.

Exudative versus Nonexudative Age-Related Macular Degeneration: Physiopathology and Treatment Options

“…Aflibercept biosimilars are FYB203 (pre-clinical investigation), ALT-L9 (entering phase I trial), CHS-2020 (pre-clinical investigation), and MYL1710 (phase III trial underway). The bevacizumab biosimilar is ONS-5010 (phase III trial completed) [88]. Medications that target both anti-VEGF and anti-PDGF pathways have also been studied to increase the therapeutic response.…”

“…Biosimilar medications replicate the therapeutic endpoint of pre-existing medications without copying their molecular structure, as occurs in generic medications [ 87 ]. There are biosimilar medications of ranibizumab, aflibercept, and bevacizumab used in neovascular AMD [ 88 ]. Ranibizumab biosimilars are razumab (approved in 2015), FYB 201 (phase III trial completed), SB-11 (phase III trial completed), Xlucane (phase III trial underway), PF582 (phase I/II trial completed), CHS3551 (pre-clinical investigation) [ 88 , 89 ].…”

“…There are biosimilar medications of ranibizumab, aflibercept, and bevacizumab used in neovascular AMD [ 88 ]. Ranibizumab biosimilars are razumab (approved in 2015), FYB 201 (phase III trial completed), SB-11 (phase III trial completed), Xlucane (phase III trial underway), PF582 (phase I/II trial completed), CHS3551 (pre-clinical investigation) [ 88 , 89 ]. Aflibercept biosimilars are FYB203 (pre-clinical investigation), ALT-L9 (entering phase I trial), CHS-2020 (pre-clinical investigation), and MYL1710 (phase III trial underway).…”

“…Aflibercept biosimilars are FYB203 (pre-clinical investigation), ALT-L9 (entering phase I trial), CHS-2020 (pre-clinical investigation), and MYL1710 (phase III trial underway). The bevacizumab biosimilar is ONS-5010 (phase III trial completed) [ 88 ].…”

KLK3 in the Regulation of Angiogenesis—Tumorigenic or Not?

“…However, some conditions such as proliferative diabetic retinopathy (PDR) or wet age-related macular degeneration (AMD) might benefit from a simultaneous blocking of VEGF-A, VEGF-C, and VEGF-D, if anti-VEGF-A therapy alone appears insufficient [49]. Indeed, a suitable biologic, the VEGF-C/VEGF-D trap OPT-302, has recently been fast-tracked by the U.S. Food and Drug Administration (FDA) for the treatment of wet AMD, and clinical trials studying combination treatments of OPT-302 with anti-VEGF-A agents are ongoing [50].…”