Dry eye disease - diquafosol
Dry eye disease is a painful, burning and irritating condition that is characterised by deficiencies or abnormalities in the eye's tear film. It is estimated to affect around 10 million people in north America alone, and is one of the most common eye complaints. Treatment currently relies heavily on the use of artificial tears to lubricate the eye, but this provides only short term symptomatic relief.
Inspire Pharmaceuticals has been investigating a drug that stimulates the eye to produce more tears. Diquafosol, formerly referred to as INS 365, is a P2Y2 receptor agonist that activates receptors on the surface of the eye and the inner lining of the eyelid. This stimulates the release of water, salt, mucin and lipids, which are the key components of natural tears.
To evaluate the ocular safety and tolerability of diquafosol as eye drops in human subjects, a double masked, placebo-controlled, randomised dose escalation study with in subject paired comparison was carried out1. Five cohorts of 10 healthy subjects were given 0.5, 1.0, 2.0 and 5.0% diquafosol in eye drops in three doses over six hours. No significant differences were seen in the number of subjects with ocular events between the placebo and drug treated groups, and diquafosol was well tolerated when administered as eye drops. No ocular tolerability issues arose with the stimulation of ocular surface P2Y2 receptors in healthy subjects.
A six month multi-centre double masked Phase III trial has been carried out in 527 patients.2 This compared the activity of diquafosol 1% and 2% eye drops with placebo. The 2% solution gave a highly statistically significant improvement in corneal staining after just two weeks, which continued to the primary six week end-point and throughout the 24-week study. Corneal staining is an indication of the degree of damage on the surface of the cornea. A dye is applied to the eye, which attaches to the cornea wherever there is damage, such as abrasions or ulceration, and this adherence of stain can be quantified by a standardised scoring procedure.
The trial also showed a statistically significant improvement in the secondary end-point of conjunctival staining. While the primary subjective end-point of clearing of the ocular symptom of foreign body sensation at week six did not reach statistical significance, it did approach it, and the number of patients who cleared foreign body sensation was consistently higher than with placebo.
Diquafosol has recently been submitted to the US FDA as a treatment for dry eye disease. It is also being investigated in aerosolised form as a potential treatment for cystic fibrosis.3,4