Several ophthalmic products are in phase III. In glaucoma, these include trabodenoson; an adenosine modulator; a fixed dose of netarsudil and latanoprost; an intracameral erodible drug-delivery system for bimatoprost, and an intracanalicular delivery system for travoprost.
In dry eye disease, products in development include tavilermide (MIM-D3) for dry eye; a new solution formulation of cyclosporine (OTX-101), and RGN 259 (Thymosin beta 4).
Lampalizumab, administered monthly by intravitreal injection, is being evaluated for geographic atrophy (Genentech). Squalamine is being evaluated in the treatment of wet age-related macular degeneration (AMD) (Ohr).
In drug delivery, an erodible anterior chamber implant of bimatoprost is being evaluated for glaucoma (Allergan). Also, a refillable reservoir is being evaluated for ranibizumab for wet AMD; suprachoroidal triamcinolone acetonide for the treatment of macular edema due to uveitis (Clearside Biomedical), and an iontophoretic system for delivery of dexamethasone to treat uveitis. A fixed-dose combination of dexamethasone and povidone-iodine is being evaluated for adenoviral conjunctivitis.
In phase II clinical development are a number of anterior chamber drug-delivery systems of prostaglandin analogues (intracanalicular, corneal rings, subconjunctival injection, and intracameral inserts).
In dry eye, there are numerous molecules of various mechanisms of action, including P-321, a phase II topical epithelial sodium channel inhibitor (Shire/Parion Sciences); two natural biologics, lubricin and lacritin; and a non-aqueous, preservative-free formulation of cyclosporine.
Abicipar pegol (an anti-VEGF DARPin) is being developed for the treatment of diabetic macular edema (Allergan). X-82, an oral tyrosine kinase inhibitor, is being developed for the treatment of wet AMD (Tyrogenex).
NS2, an inhibitor of aldehyde formation, is in development for allergic conjunctivitis and also uveitis (Aldeyra Therapeutics).
Emixustat is being evaluated for several retinal disorders, including proliferative diabetic retinopathy and Stargardt disease (Acucela). Numerous molecules and delivery systems are in earlier stage clinical and preclinical development—but beyond the scope of this brief report.
Two approvals from outside the United States are ripasudil (Glanatec, Kowa Co. Ltd.), a rho-kinase inhibitor approved in Japan in 2014 for the treatment of glaucoma,4 and an novel formulation of cyclosporine (Ikervis, Santen), approved for the treatment of severe dry eye disease in Europe in 2015.5
While ophthalmologists are fortunate to have many novel treatments in development, changes in the American healthcare system continue to raise the hurdles for financial success. For example, in the treatment of glaucoma and ocular hypertension, physicians and patients have generic alternatives in all of the classes.
This is not to say that the generic products are equivalent in all features—however, manufacturers of branded products will have to provide evidence to U.S. insurance companies to support the incremental cost.6