Challenges faced in clinical trials for chronic allergic conjunctivitis

Abstract

Allergic conjunctivitis is an inflammatory disorder at the ocular surface that affects 40% of Americans with allergic symptoms. Treatment of chronic ocular allergy is currently limited and is often associated with severe side effects. Development of new therapeutics to address this unmet need has proved challenging due to the highly variable nature of this disorder. Historically, clinical studies for the evaluation of pharmacological agents for the treatment of ocular allergy relied on seasonal and/or chamber models, both of which are associated with a number of limitations resulting in inconsistent and, oftentimes, non-reproducible study conditions. The development of the conjunctival allergen challenge model in 1990 provided a highly effective means for the study of ocular allergy. Recently, modifications to this model with multiple successive allergen challenges have shown to mimic the chronic allergic response and will likely be pivotal in the development of new therapeutics for chronic allergic conjunctivitis.

Keywords:

• alcaftadine
• allergen-specific immunotherapy
• allergic conjunctivitis
• chronic inflammation
• cyclosporine A
• dexamethasone
• levocabastine
• mapracorat
• olopatadine
• tacrolimus

Financial & competing interests disclosure

The authors were supported by Ora, Inc. P Gomes, C Slocum and L Smith are employees of Ora, Inc. M Abelson is chairman of the board at Ora, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Allergy is the fifth leading group of chronic diseases, affecting 50 million Americans.

• Ocular allergies affect 40% of Americans with allergic symptoms.

• Current therapies, such as antihistamines and mast cell stabilizers, are effective in providing temporary relief from ocular allergic symptoms by targeting the acute response.

• Treatment for chronic allergic conjunctivitis is currently limited to corticosteroids and is oftentimes associated with a number of severe side effects.

• Development of new therapies has relied on seasonal and chamber studies, but has seen limited success due to an inconsistent baseline for the studies, resulting from a number of variables, such as allergen exposure.

• The creation of the conjunctival allergen challenge model in 1990 has provided a highly reproducible situation for the study of ocular allergy and has been used in the development of almost every anti-allergic agent available today.

• Modification of the conjunctival allergen challenge model, with repeated allergen challenges, has proved to mimic the chronic allergic response and will likely be pivotal in the development of new therapies for chronic allergic conjunctivitis.

• Future therapies currently being explored for the treatment of allergic conjunctivitis include allergen desensitization immunotherapy, selective glucocorticoid receptor agonist, Toll-like receptor modulators and Syk inhibitors.