Regulatory Decision Summary for Xipere

The purpose of this New Drug Submission (NDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Xipere, filed by Bausch & Lomb Inc. This submission was filed for Xipere (Triamcinolone Acetonide injectable suspension, 40 mg/mL, for suprachoroidal injection), for the treatment of macular edema (ME) associated with uveitis in adults.

The proposed indication was supported by the results from one pivotal Phase 3, randomized, masked, sham-controlled, multicenter study (PEACHTREE; CLS1001-301) in 160 subjects with non-infectious uveitis with macular edema. Subjects were randomized to receive either two unilateral suprachoroidal injections of 4 mg of triamcinolone acetonide (Xipere; N = 96) or two sham injection procedures (Control; N = 64), administered 12 weeks apart. The study population included subjects 18 years to 92 years of age (mean age of 50.24 years), and predominantly Asian (72/160 subjects) and White (65/160 subjects).

The primary efficacy endpoint was the proportion of subjects with a change from Baseline of ≥15 letters in Early Treatment Diabetic Retinopathy Study (ETDRS) letters read in Best Corrected Visual Acuity (BCVA) at Visit 8 (Week 24). The primary efficacy endpoint was met. At Week 24, the proportion of subjects who gained ≥15 ETDRS letters in BCVA from Baseline was higher in the Xipere arm (45/96 subjects [46.9%]) compared to the Control arm (10/64 subjects [15.6%]) (difference in percentages: 31.25% [95% CI:15.5, 45.9]). The difference was statistically significant (p<0.001).

The efficacy of Xipere was further supported by the secondary efficacy endpoint of mean change from Baseline in Central Subfield Thickness (CST) as measured by spectral domain optical coherence tomography (SD-OCT) at Week 24. The results showed a large decrease in CST for subjects in the Xipere arm (mean of -152.6 µm [standard deviation 159.14]) (median: -125.0 µm) compared to subjects in the Control arm (-17.9 µm [150.98]) (median: 0 µm).The difference was statistically significant (p <0.001).

The safety of Xipere was assessed in the pivotal study. Overall, the majority of subjects experienced Treatment-eye treatment-emergent adverse events (TEAEs) (86/160 subjects [53.8%]). The percentage of patients with 1 or more ocular adverse events (AEs) was 51.0% in the Xipere arm and 57.8% in the Control arm. The percentage of patients with ocular AEs considered by the investigator to be treatment-related was 30.2% (29/96 subjects) in the Xipere arm and 12.5% (8/64 subjects) in the Control arm. The most frequently reported ocular AEs occurring at a greater frequency in the Xipere arm compared to Control were eye pain at time of procedure (experienced by 9.4% vs. 0% of subjects, respectively), elevated intra-ocular pressure (IOP) associated with corticosteroid (experienced by 15.6% vs. 0% of subjects, respectively), and cataract cortical and subcapsular (experienced by 5.2% vs. 0% of subjects). One serious AE was experienced in the Treatment-eye in the Xipere arm: retinal detachment was reported but was not considered related to study treatment. In addition, there were five AEs leading to study drug discontinuation in each treatment group (experienced by 5.2% and 7.8% of subjects in the Xipere and Control arm, respectively). The majority of the events were mild to moderate in intensity. Only two non-ocular TEAEs of vomiting and headache, were reported in the Xipere arm and were considered related to study drug.

No safety concerns with respect to systemic effects of corticosteroids were identified with suprachoroidal administration of triamcinolone acetonide suspension 4 mg every 12 weeks, as pharmacokinetic studies demonstrated low systemic concentration of triamcinolone acetonide. Known safety events associated with corticosteroids, including the potential for the drug to cause a suppression of the hypothalamic-pituitary-adrenal (HPA axis), are adequately labelled for in the approved Product Monograph.

The chemistry and manufacturing information submitted for Xipere 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 Xipere (triamcinolone acetonide injectable suspension, 40 mg/mL, for suprachoroidal injection) 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 Xipere, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.