Regulatory Decision Summary for Lataneo PF

The purpose of this New Drug Submission (NDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drug Regulations, for Lataneo PF, filed by Orimed Pharma.

This submission was filed for Lataneo PF (latanoprost ophthalmic solution 0.005% w/v (50 µg/mL), preservative free) for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG), ocular hypertension (OHT) and chronic angle-closure glaucoma who underwent peripheral iridotomy or laser iridoplasty.

In the current submission, the Sponsor is seeking approval of a preservative-free (PF) formulation of latanoprost (Lataneo PF), which contains the same concentration of latanoprost (0.05%) as marketed preserved latanoprost ophthalmic solution, but does not contain the preservative benzalkonium chloride (BAK).

The proposed indication is supported by a single Phase 3, randomized, active-controlled, observer-blind, non-inferiority clinical trial conducted in patients with Open Angle Glaucoma (OAG), or Ocular Hypertension (OHT). A total of 170 patients were randomized, with 86 treated daily with Lataneo PF and 84 with a BAK-preserved latanoprost ophthalmic solution (0.005% w/v). Demographic and baseline disease characteristics were comparable between treatment arms.

The primary efficacy endpoint was the difference between Lataneo PF and the preserved latanoprost in mean change in intraocular pressure (IOP) from baseline at a single timepoint (08:00) at week 12 in the per-protocol (PP) population. Lataneo PF was considered to be non-inferior to preserved latanoprost at this time point if the upper limit of the 95% confidence interval (CI) for between-group difference did not exceed 1.5 mm Hg. Efficacy was additionally assessed at 08:00, 12:00, and 16:00 at weeks 2, 6, and 12.

Daily treatment with Lataneo PF and preserved latanoprost resulted in a statistically and clinically significant mean decrease from baseline in IOP at all measured time-points. Mean changes from baseline IOP ranged from -7.94 to -8.24 mm Hg for Lataneo PF and -7.82 to -8.17 mm Hg for preserved latanoprost at week 12 at all time-points. The primary efficacy endpoint was achieved. At 08:00 at week 12, Lataneo PF was non-inferior to preserved latanoprost and the upper limit of the 95% CI did not exceed 1.5 mm Hg (point estimate of the difference: 0.100 mm Hg (95% CI: -0.646, 0.847), p = 0.791). Across all additional timepoints, the 95% CIs were within the ±1.5 mm Hg NI margin, and within the tighter clinically relevant NI margin of ±1.0 mm Hg at Weeks 6 and 12, indicating comparable efficacy between the test and reference once steady state was achieved.

Latanoprost ophthalmic solution has been marketed in Canada since 1997; therefore, it has a well-established safety profile in the indicated population. Overall, there were no safety issues or clinically relevant treatment group differences between Lataneo PF and preserved latanoprost. A total of 53 patients experienced adverse events (AEs), the majority of which were ocular (Lataneo PF: 28; preserved latanoprost: 22). The proportion of treatment-related AEs was comparable between groups (Lataneo PF: 51.1%; preserved latanoprost: 51.3%) and most events resolved before the end of the study at week 12 (Lataneo PF: 75.6%; preserved latanoprost: 89.7%). The most frequent ocular AEs were instillation site burning and increased IOP, each reported by 8 patients (19%) in both groups. Most ocular AEs were mild in severity (Lataneo PF: 79.5%; preserved latanoprost: 66.7%), with the remainder moderate. All AEs have been adequately captured in the Product Monograph (PM).

The chemistry and manufacturing information submitted for Lataneo PF has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

The final labelling and Product Monograph were considered acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Lataneo PF for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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