Regulatory Decision Summary for Ixifi

This submission was submitted to support the authorization of Ixifi, a biosimilar to the Canadian authorized reference biologic drug, Remicade, for all of the indications currently authorized to Remicade on the basis of comparative quality, non-clinical and clinical studies.

Ixifi was assessed in two clinical trials. Study B5371001 was a randomized, double-blind, parallel-group, single-dose study in healthy adult subjects (n = 151). This study demonstrated pharmacokinetic comparability between the 3 versions of infliximab: Ixifi, Remicade-European Union (EU) and Remicade- United States (US).

Study B5371002 was a pivotal Phase 3, randomized, double-blind, 2-arm, parallel group, multicentre study comparing the efficacy and safety of Ixifi and Remicade-EU in patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to methotrexate. Subjects were randomized in a 1:1 ratio to receive either 3 mg/kg of Ixifi (n = 323) or Remicade-EU (n = 326) intravenously at Weeks 0, 2 and 6, followed by administration every 8 weeks until Week 70. The primary efficacy endpoint was the proportion of subjects achieving a 20% or greater improvement in American College of Rheumatology (ACR) clinical response (ACR20) at Week 14. The ACR20 clinical response at Week 14 between Ixifi and Remicade-EU met Health Canada’s similarity margin criteria. The most common adverse events reported in at least 3% of subjects during the main treatment period included infusion-related reactions, alanine aminotransferase (ALT) increased, and nasopharyngitis. Ixifi was not clinically meaningfully different from Remicade-EU with respect to treatment-emergent adverse events, serious adverse events, deaths, anti-drug antibodies, and neutralizing antibodies. The safety findings for Ixifi was consistent with previous observations for other authorized infliximab drugs.

Overall, based on the totality of evidence derived from the comparative structural, analytical and functional, non-clinical and clinical data, similarity between Ixifi and Remicade has been demonstrated. Furthermore, the scientific rationale provided by the sponsor to support the authorization of Ixifi in each indication held by the reference biologic drug is considered adequate and is in line with Health Canada’s biosimilar guidance document. Therefore, the benefit-risk profile of Ixifi is considered favourable for the treatment of adult rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and adult and pediatric ulcerative colitis and Crohn’s disease including adult patients with fistulising Crohn’s disease.

For more information on Health Canadas decision, please view the Summary Basis of Decision.