Regulatory Decision Summary for Zimed PF

This New Drug Submission (NDS) was filed to obtain market authorization for Zimed PF (bimatoprost ophthalmic solution 0.03% w/v, preservative-free) for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Upon review, the modified indication for the reduction of intraocular pressure in adult patients with open-angle glaucoma or ocular hypertension was approved.

Health Canada considers that the benefit-harm-uncertainty profile of Zimed PF (bimatoprost ophthalmic solution, 0.03% w/v, preservative-free) is favourable for the reduction of elevated intraocular pressure in adult patients with open-angle glaucoma or ocular hypertension.

The indication is supported by the results from a single Phase 3 randomized, active-controlled, non-inferiority study conducted in adult patients with open-angle glaucoma or ocular hypertension. A total of 597 patients were enrolled, with 302 treated daily with a preservative-free bimatoprost ophthalmic solution (0.3 mg/mL) and 295 treated daily with a benzalkonium chloride (BAK) preserved bimatoprost ophthalmic solution (0.3 mg/mL). The primary efficacy endpoint was derived from intraocular pressure (IOP) measurements. The primary efficacy analysis was the change from baseline (follow-up minus baseline) in worse eye IOP at 0, 2, and 8 hours post-administration at week 12 in the per-protocol (PP) population. Preservative-free bimatoprost was considered to be non-inferior to preserved bimatoprost at each time-point if the upper limit of the 95% confidence interval (CI) for between-group difference did not exceed 1.5 mmHg.

The Phase 3 study showed that daily treatment with both preservative-free and preserved bimatoprost resulted in a statistically and clinically significant mean decrease from baseline in worse eye IOP at all follow-up time-points (p < 0.001). Mean changes from baseline IOP ranged from -7.49 to -5.93 mmHg for preservative-free bimatoprost and -7.77 to -6.06 mmHg for preserved bimatoprost across the study duration as measured on weeks 2, 6, and 12 at 0, 2, and 8 hour time-points in the PP population. The between-group difference in mean worse eye IOP was < 0.4 mmHg at all time-points and was not statistically or clinically significant. The study also demonstrated that preservative-free bimatoprost was non-inferior to preserved bimatoprost at each hour evaluated (hours 0, 2, and 8) during the week 12 visit for worse eye IOP change from baseline in the PP population. Specifically, the upper limit of the 95% CI for between-treatment difference did not exceed 1.5 mmHg. Notably, the upper limit did not exceed 0.75 mmHg at any week 12 time-point and non-inferiority was additionally demonstrated in the intent-to-treat (ITT) population.

Bimatoprost ophthalmic solution has been marketed in Canada since 2001; therefore, it has a well-established safety profile in the indicated population. The preservative-free and preserved formulations were well-tolerated in the submitted studies, and no notable difference in safety between the formulations was observed. In the pivotal study, the most common adverse events for both preservative-free and preserved bimatoprost included conjunctival hyperaemia (23.9% and 26.1%, respectively), eye pruritus (4.0% and 4.1%), and punctate keratitis (3.0% and 3.1%). A total of five patients discontinued due to adverse events (2/301 treated with preservative-free bimatoprost and 3/295 treated with preserved bimatoprost). Overall, no serious adverse events were ocular or considered to be treatment related. Adverse events reported in the post-market setting are captured in the Product Monograph.

Overall, the anticipated benefits of Zimed PF (bimatoprost ophthalmic solution, 0.03% w/v, preservative-free) are expected to outweigh its risks under the conditions of use recommended in the Zimed PF Product Monograph at this time.

For further details about Zimed PF, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.