Regulatory Decision Summary for BEPREVE

Health Canada considers that the anticipated benefits of Bepreve outweigh its potential risks for the treatment of itching associated with allergic conjunctivitis.

The pivotal trials in support of this proposed indication demonstrated a statistically significant and clinically relevant improvement in itching, but not redness, for the treatment of allergic conjunctivitis.

The pediatric population ≤10 years of age are not considered reliable historians with reporting ocular itching scores and were therefore excluded from the efficacy pivotal trials. In addition allergic conjunctivitis cannot be consistently diagnosed in children less than 2-3 years of age. For older children aged 3-10, there are no published studies suggesting differences in allergic conjunctivitis mechanisms or treatment benefits compared to older patients. Therefore, the sponsor proposed extrapolating the efficacy in the age group of 3-10 years from clinical trials conducted in pediatric patients greater than 10 years of age and from adults. Bepreve was clinically efficacious based on the primary efficacy variable of ocular itching in the subpopulation group (ages 11-17) in both pivotal trials.

A safety study was performed, with greater exposure to Bepreve as compared to the pivotal trials, specifically designed to include pediatric patients 3 years of age and older and to examine any potential long-term effects on corneal health. Apart from some taste-related adverse events upon product instillation, no major safety concerns were identified in either the adult or pediatric subpopulations. Therefore the data also favour the use of Bepreve in the subpopulation, ages 3-10.

Non-clinical studies showed that Bepreve was not irritating to the anterior segment of the eye. Adverse reactions reported in clinical trials and from post-marketing experience since product launch in the United States in 2009, are described in the Product Monograph. The most common adverse reaction occurring in about 25% of patients was a mild taste following instillation. Other adverse reactions occurring in about 2-5% of patients were eye irritation and headache. Some safety issues from post-marketing experience include anaphylactic/hypersensitivity reactions and absorption of benzalkonium chloride by soft contact lenses. Uncertainties such as safety in pregnancy and lactation and safety in children under 3 years of age are also addressed in the Product Monograph.

In summary Bepreve exhibits an overall positive benefit/risk ratio for the treatment of itching in allergic conjunctivitis in patients 3 years of age and older, under the conditions of use described in the Product Monograph.