New strategy for treating dry eye

Reproxalap could represent important treatment for patients with dry eye disease

Sean Henahan

Posted: Saturday, September 1, 2018

Reproxalap, a novel agent that targets toxic aldehydes in tear film, could offer a new option in the treatment of dry eye disease, reported researchers at the Association for Research in Vision and Ophthalmology (ARVO) 2018 Annual Meeting.

Fifty-one patients with active dry eye disease received one of three formulations of the drug in a randomised, double-masked, phase IIa clinical trial. The formulations tested were topical ocular 0.1% reproxalap, 0.5% reproxalap or a 0.5% lipid formulation of reproxalap four times daily. Pooled results after 12 weeks of treatment showed statistically significant changes in the Symptom Assessment in Dry Eye (SANDE) score, the ocular discomfort score, the overall four-symptom score, Schirmer’s tests, osmolarity and corneal staining with lissamine green, announced David Clark MD, Chief Medical Officer at Aldeyra Therapeutics.

The study also showed a modest dose response, with improvement in symptoms seen after only one week of therapy. Improvement in corneal staining and osmolarity correlated with reduction in levels of tear reactive aldehyde species. The treatment was safe and well tolerated. A follow-on phase IIb trial is now under way that aims to enrol 300 patients with active disease, randomised equally to receive either 0.1% reproxalap, 0.25% reproxalap or vehicle for three months.

“Reproxalap could represent an important treatment for many patients that suffer from dry eye disease. The activity demonstrated within one week of therapy in the phase IIa clinical trial suggests that reproxalap could have significant potential for the treatment of dry eye disease,” said Gary Foulks MD, FACS, Professor Emeritus, Department of Ophthalmology & Visual Sciences at the University of Louisville, US.

The treatment represents a different approach to dry eye therapy than current options. It is based on the idea that pro-inflammatory aldehyde mediators may contribute to ocular inflammation. Reproxalap acts to sequester pro-inflammatory reactive aldehyde species. The developers hope that the topical ocular aldehyde trap approach could augment existing dry eye therapy, ideally reducing the need for corticosteroids and their attendant risks.

A phase III clinical trial with reproxalap is also under way for the treatment of allergic conjunctivitis. That trial will also enrol 300 patients with active disease, randomised equally to receive either 0.1% reproxalap, 0.25% reproxalap or vehicle for three months. In a phase II trial, patients reported rapid resolution of ocular itching following administration of the drug.

Topical reproxalap is also being studied in a phase III clinical trial as a treatment of non-infectious anterior uveitis. Toxic aldehydes are known to be associated with inflammation, fibrotic changes and lipid destruction that lead to surface irritation, pain, photophobia, redness and vision loss in that rare disease.

David Clark:
Gary Foulks: