Regulatory Decision Summary for Omlyclo

The purpose of this new drug submission (NDS) was to seek market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Omlyclo filed by Celltrion Inc., a proposed biosimilar to the Canadian reference biologic drug Xolair (omalizumab) for use in the treatment of allergic asthma in adults and adolescents 12 years and above and children 6 to <12 years of age, chronic rhinosinusitis with nasal polyps in adults and chronic spontaneous urticaria in adult and adolescent 12 years and above.

Omlyclo is a proposed biosimilar drug that contains the same active pharmaceutical ingredient omalizumab as the reference biologic drug, Xolair. In Canada, Xolair was first authorized in 2004 and is currently authorized for use for the treatment of allergic asthma in adults and adolescents 12 years and above and children 6 to <12 years of age, chronic rhinosinusitis with nasal polyps in adults and chronic spontaneous urticaria in adult and adolescent 12 years and above.

Pharmacokinetic similarity between Omlyclo and the reference biologic drug, Xolair was supported by a Phase 1 PK study conducted in healthy subjects in which the 90% confidence interval for the relative C_max (maximum serum concentration) and area under the concentration-time curve (AUC) from time zero to the last quantifiable concentration (AUC_last) were contained entirely within Health Canada’s prespecified comparative pharmacokinetic biosimilarity margin of 80.0% to 125.0%. Likewise, the comparative clinical similarity between the products for clinical efficacy, safety and immunogenicity was demonstrated in a randomized, active-comparator (European Union-approved Xolair) trial in patients with chronic spontaneous urticaria. The 90% confidence interval for the primary endpoint of mean change from baseline in Weekly Itch Severity Score (ISS7) was contained within the pre-defined equivalence margin and review of the safety data did not identify any meaningful differences in the reporting of adverse events, abnormal laboratory tests, electrocardiograms (ECGs) or physical exam findings between the exposure groups. A small difference was noted in the development of anti-drug antibodies between Omlyclo and Xolair that did not impact the clinical efficacy or safety.

Review of the information provided by the sponsor and the published literature support the extrapolation of the results of this study to asthma and severe chronic rhinosinusitis with nasal polyps (CRSwNP) given the common pathophysiology of these disorders and the demonstrated similarity of the pharmacokinetics and safety of omalizumab in these populations.

The proposed indications and recommended dose regimens for Omlyclo are identical to the reference biologic drug, Xolair. The totality of evidence reviewed in the clinical assessment is supportive of biosimilarity between Omlyclo and the reference biologic drug, Xolair; establishment of biosimilarity between Omlyclo and Xolair is also contingent on the pivotal assessment of comparative physiochemical characteristics and functional properties. Overall, from a clinical perspective, the benefit-risk profile of Omlyclo is consistent with Xolair and is favourable for all indications held by the reference biologic drug.

An updated Risk Management Plan (RMP) for Omlyclo 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.

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

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

Overall, the benefit-harm-uncertainty profile was favourable for Omlyclo 75mg/0.5mL and 150mg/1.0mL 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 Omlyclo, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.