Regulatory Decision Summary for Mezera

This Supplemental New Drug Submission (SNDS) was filed to obtain market authorization for a new 1,000 mg strength of Mezera (mesalazine delayed-release tablets).

The proposed 1 g strength was supported by one pivotal Phase 3 study (SAT-25/UCA). This study was a double-blind, double-dummy, randomised, multi-centre, comparative, non-inferiority trial in 306 patients aged 18 to 75 years with mild to moderately active ulcerative colitis in Europe. For eight weeks, 151 patients were treated with 1 g Mezera three times daily (TID; 3 g/day) and 155 patients were treated with 2 x 500 mg Mezera TID (3 g/day).

The primary efficacy endpoint was the percentage of patients in clinical remission at the final examination, defined as the Clinical Activity Index (CAI) ≤4 with stool frequency subscore of 0 and rectal bleeding subscore of 0. The CAI is an index scale ranging from 0 to 31 points and is the sum score of seven variables: bowel movement frequency, presence of blood, general well-being, abdominal pain, temperature due to colitis, extraintestinal manifestations, and laboratory findings (erythrocyte sedimentation rate and hemoglobin). The primary efficacy endpoint was achieved. 1 g Mezera TID was non-inferior to the active control, 2 x 500 mg Mezera TID, with a non-inferiority margin of 8.0% (95% confidence interval = -9.6%; p-value = 0.0043). Clinical remission at week 8 was achieved by 46.6% of patients treated with 1 g Mezera TID compared to 38.6% of patients treated with 2 x 500 mg Mezera TID in the per protocol (PP) population. Sensitivity analyses performed were supportive of and confirmed the primary analysis results. Notably, the majority of patients, regardless of treatment arm, stated that they preferred the intake of one tablet over two tablets.

The safety of 1 g Mezera is consistent with the well-documented safety profile for mesalazine. In the pivotal trial, the most commonly reported treatment-emergent adverse events (TEAEs) were: investigations, gastrointestinal disorders, and infections and infestations. Nine events were determined to be drug-related TEAEs, including hepatic reactions, investigations, and musculoskeletal and connective tissue disorders. One severe TEAE was observed in the study (worsening of symptoms of ulcerative colitis; not drug-related; seen in 2 x 500 mg Mezera arm).

Overall, the benefit-harm-uncertainty profile of 1 g Mezera delayed-release tablets for the induction of remission of active, mild to moderate ulcerative colitis is favourable. A Notice of Compliance is recommended.

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