Dry Eye Dx and Tx

What's in Store for Dry Eye?

By Katherine M. Mastrota, MS, OD, FAAO

It is hard to say what the next dry eye therapeutic breakthrough will be, but there are currently a number of promising candidates in the field. Let's take a closer look at a few of them.

Dry Eye Options Soon to Come

NGF Mimetic Novel to the potential dry eye treatment arena is Mimetogen's small-molecule mimetic of nerve growth factor (NGF), MIM-D3. NGF is a naturally occurring protein in the eye that is responsible for maintaining corneal nerves as well as epithelium, mucin, and tear production. NGF performs multiple activities with potential benefit in dry eye disease (DED) including neurotrophic effects, corneal healing, and mucin secretion. Recent Phase 2 results for MIM-D3 presented in the poster session at the 2012 Association for Research in Vision and Ophthalmology (ARVO) meeting demonstrated statistically significant improvements in signs and symptoms of DED (Meerovitch et al, 2012). These preliminary results are very promising for the use of MIM-D3, a first-in-class therapy.

A3 Adenosine Receptor Agonist Another first-in-class drug in development is Opthalix's CF101, an A3 adenosine receptor agonist. A3 adenosine receptors are involved in inhibiting neutrophil degranulation in neutrophilmediated tissue injury and may have neuroprotective effects. This small-molecule, orally bioavailable drug with proven efficacy in Phase 2 clinical studies (Avni et al, 2010) has an excellent safety profile and is currently being developed for ophthalmic indications including dry eye syndrome (Phase 3), glaucoma (Phase 2), and uveitis. CF101 is also being developed for the treatment of autoimmune inflammatory diseases including rheumatoid arthritis (Phase 2b) and psoriasis (Phase 2/3).

Topical Protein Eleven Biotherapeutics, a biopharmaceutical company designing and engineering novel and differentiated protein-based biotherapeutics, presented preclinical data for EBI-005, a topically applied protein, at ARVO 2012 (Furfine et al, 2012). The data demonstrate optimal properties of EBI-005 for treating DED such as high potency, thermal stability, and very low systemic exposure. EBI-005 is the first ever Interleukin-1 (IL-1) receptor inhibitor protein for topical administration that is optimized for treating DED and other ocular surface inflammatory disorders. Targeting IL-1 is one of the most promising therapeutic approaches for treating dry eye disease because IL-1 is a critical mediator of the inflammatory cascade that causes both the surface disease and symptoms suffered by patients who have DED.

Integrin Antagonist Sarcode Bioscience, Inc. has completed patient enrollment in its first Phase 3 clinical study of SAR 1118, a first-in-class small-molecule integrin antagonist (integrins mediate cell-cell and cell-matrix interaction and communication) that inhibits T cell inflammation by blocking the binding of two key surface proteins (LFA-1 and ICAM-1) that mediate the chronic inflammatory cascade associated with DED.

Immunomodulator Finally, we have Pfizer's CP-690, tofacitinib. This immunomodulator is under investigation in multiple trials for multiple indications, including transplant rejection, inflammatory bowel disease, psoriasis, rheumatoid arthritis, and DED. Tofacitinib is a Janus kinase inhibitor. Janus kinase is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals. In a recent phase 1/2 study, tofacitinib demonstrated a trend for improving both signs and symptoms of dry eye (Liew et al, 2012). All doses of tofacitinib exhibited a reasonably safe profile and were well tolerated by patients who have DED.

Promising Treatment Ahead

There is exciting promise for new agents in dry eye disease. I, with you, wait with bated breath. CLS

For references, please visit www.clspectrum.com/references.asp and click on document #200.