Regulatory Decision Summary for Remsima SC

The purpose of this Supplement to a New Drug Submission (SNDS) for Remsima SC, filed by Celltrion Healthcare Co., Ltd was to expand the recommended use of a subcutaneous formulation of infliximab (Remsima SC) to include the maintenance treatment of adult patients with moderately to severely active Crohn’s disease and/or ulcerative colitis who have failed conventional therapy. After evaluation of the submitted data package, Health Canada authorized Remsima SC for the maintenance treatment of both adults with moderately to severely active Crohn’s disease and adults with moderately to severely active ulcerative colitis who have had an inadequate response or were intolerant to conventional therapy. In these patient populations, Remsima SC should only be used as maintenance therapy after the completion of an induction period with intravenous infliximab.

• Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic and progressive disease that adversely impacts the gastrointestinal tract. IBD is associated with a high disease burden and its prevalence in Canada is among the highest worldwide.

• Infliximab is one of many TNFα inhibitors authorized in Canada to treat various chronic inflammatory diseases, including Crohn’s disease and ulcerative colitis. However, to date, only intravenous formulations of infliximab have been authorized for use for these two indications. Remsima SC is a subcutaneous formulation of infliximab.

• Authorization was based on two Phase 3, 54-week, randomized, double-blind, placebo-controlled studies (CT-P13 3.8 and CT-P13 3.7). Adult patients with CD (n = 343) and UC (n = 438) who achieved clinical response following an induction dosing regimen administered with intravenous infliximab were randomized to receive either Remsima SC or placebo as their maintenance regimen. The maintenance dose administered was 120 mg administered subcutaneously every two weeks, beginning 4 weeks after the last intravenous infliximab administration.

• The co-primary efficacy endpoints in the study with CD patients (CT-P13 3.8) were the proportion of subjects in clinical remission and endoscopic response at Week 54. Other key secondary endpoints included the proportion of subjects achieving CDAI-100 response, clinical remission (based on abdominal pain and stool frequency), endoscopic remission and corticosteroid-free remission. The primary endpoint in the study with UC patients (Study CT-P13 3.7) was the proportion of subjects in clinical remission at Week 54. Other key secondary endpoints included the proportion of subjects achieving clinical response, endoscopic-histologic mucosal improvement, and corticosteroid-free remission. There was a statistically significant and clinically meaningful benefit for Remsima SC compared to placebo for these endpoints.

• The safety profile of infliximab, administered intravenously and subcutaneously, is well-established. The observed safety profile of Remsima SC in adult patients with CD and adult patients with UC is considered consistent with that reported for other authorized indications. No additional risks were identified in Studies CT-P13 3.8 and CT-P13 3.7. Commonly reported TEAEs (≥3%) in CD and/or UC patients that were reported more frequently in patients receiving Remsima SC included: abdominal pain, alanine aminotransferase increased, anaemia, arthralgia, blood creatinine phosphokinase increased, COVID-19, diarrhea, headache, hypertension, injection site reaction, injection related reaction, neutropenia, and upper respiratory tract infection.

• Overall, based on the data evaluated as part of this submission, the benefit-risk profile of Remsima SC used as per the recommended dosing regimen, is considered to be favourable for the maintenance treatment of both adult patients with moderately to severely active CD and adult patients with moderately to severely active UC.

An updated Risk Management Plan (RMP) for Remsima SC was reviewed by Health Canada and considered acceptable. Risks have been communicated in the approved Product Monograph and will continue to be monitored post market as outlined in the Risk Management Plan, with routine and non-routine pharmacovigilance activities.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

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