New Pharmacological Treatments for Dry Eye Disease

Authors: Gary D Novack

Publish Date: 2013/03/06

Volume: 1, Issue: 2, Pages: 75-79

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Abstract

The impact of dry eye disease on patient’s health visual function and quality of life may be substantial At present the only approved pharmacological treatment in the US or Canada is Restasis® cyclosporine ophthalmic emulsion In Japan three products are approved Hyalein® hyaluronic acid Diquas® diquafasol and Mucosta® rebamapide No pharmacological treatment is currently approved in Europe In this article I will provide updates on “new” pharmacological treatments—ie those beyond any approved as of January 2012 primarily those in clinical trials Novel treatment for pharmacological management of dry eye disease is an area of active clinical development as evidenced by numerous recently completed or ongoing studies The pharmacological agents in evaluation cover a wide range of putative mechanisms of action However firms developing these agents continue to be challenged by the limitations of animal models of efficacy relatively small and variable clinical effects in Phase 2 and the investment in time and resources required for Phase 3The impact of dry eye disease on patient’s health visual function and quality of life may be substantial as discussed in the Dry Eye Workshop DEWS in 2007 1 Like ocular surface disease itself management and therapy is complex and multifactorial The Management and Therapy Subcommittee of DEWS recommended a staged additive approach to management depending upon the severity of the disease and the response to treatments The categories of pharmacological treatments included artificial tear substitutes gels and ointments regulated by the US FDA under the overthecounter ophthalmic monograph 21 CFR 349 2 3 antiinflammatory agents topical cyclosporine and corticosteroids and oral omega3 fatty acids secretagogues serum and systemic immunosuppressives 4• The regulatory issues in developing and approving ocular pharmacological treatments for dry eye was reviewed at a tear film and ocular surface TFOS/Association for Research in Vision and Ophthalmology ARVO symposium As of January 2012 the only approved pharmacological treatment in the US or Canada is Restasis® cyclosporine ophthalmic emulsion In Japan three products are approved Hyalein® hyaluronic acid Diquas® diquafasol and Mucosta® rebamapide No pharmacological treatment is currently approved in Europe 5•United States Patent database http//wwwusptogov/ for patents issued between 1 January 2005 and 30 November 2012 containing the words “dry eye” or “sicca” in the title Patents issued between 1 January 2002 and 31 December 2004 may be found in a previously published article 8None of these sources is absolutely inclusive While I have made best efforts to be thorough it is possible that the above approaches missed some therapies Also sponsors do not always notify the public when a particular product is no longer under active development Small companies in particular must raise funds frequently in order to pay the costs of development There is one final caveat—the use of the clinical development phase is a continuum not an absolute and thus may not correctly and unambiguously describe the development stage 9Clinicaltrialsgov US based has 246 studies meeting the criteria of “dry eye” or “sicca” 135 of which are in the US 27 are in China and 15 are in Japan Of these 246 studies 37 are currently “open” meaning recruiting not yet recruiting or unknown Further refining to those started in 2010 or later my definition of “new” and limiting to studies on pharmacological agents there are 42 The European registry had 18 studies meeting the criteria of which 6 met the further refinement The Japanese registry had 12 studies meeting the criteria of which 3 met the further refinement There is some crossregistration of studies on different online registries which is consistent with the guidances Entries are not always current and thus “conducting” versus “conducted” is a matter of judgment for the user I used the organizational schema from the DEWS report 4• with the category of “other” for those agents for which the mechanism of action or clinical effects are not yet well knownHyaluronic acid in various formulations continues to be evaluated by many firms including Alcon River Plate and Seikagaku SI614 This agent has the rare position of being regulated in the US as a drug a device or an excipient depending upon the product

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