Regulatory Decision Summary for Noromby

Noromby (Enoxaparin sodium) is a biosimilar biologic drug to the Canadian authorized reference product, Lovenox. Both contain the active pharmaceutical ingredient, enoxaparin sodium. Enoxaparin Sodium (marketed as Lovenox since 1993) has proven to have a favourable benefit/risk balance for the treatment of patients with thromboembolic disorders.

For non-clinical and clinical review, the sponsor submitted a nonclinical data package, which included pharmacodynamic (PD) and immunogenicity program elements.

The clinical development program consisted of one pivotal and one supportive pharmacodynamic (PD) studies in healthy volunteers:

1. The pivotal study met its primary objective of demonstrating PD equivalence of Noromby and Lovenox. The primary statistical analysis showed that the 95% confidence intervals (CIs) of the geometric mean ratios for the primary PD parameters/endpoints for anti-factor Xa (anti-F_Xa) and anti-factor IIa (anti-F_IIa) were enclosed within the pre-specified equivalence interval of 80.00% to 125.00%. These results were supported by the secondary statistical analysis, which showed that the two formulations were bioequivalent based on the PD parameters/endpoints for baseline adjusted Tissue Factor Pathway Inhibitor (TFPI) levels.
2. The supportive study satisfactorily demonstrated that the reference product Lovenox 100 mg/mL; 100 mg SC) and the test product (Noromby; 100 mg SC) were bioequivalent as well. The bioequivalence of the two products was supported by the pre-specified statistical analysis of the PD parameters for anti-IIa activity of Area under the effect curve from time 0 to the last measured activity (T) (AUEC_0-t) and anti-IIa_max, but the data for AUEC_0-inf were not included in the statistical analysis due to the small number of subjects in the two treatment groups. The PD bioequivalence analyses of the baseline-adjusted TFPI activity and the ratio of area under the effect curves (RAUEC) supported the PD bioequivalence analyses of anti-Xa and anti-IIa activities. The post hoc analyses of the PD parameters using the more stringent criterion of a 95% CI were consistent with the pre-specified analyses using a 90% CI with the 80 to 125% PD bioequivalence (BE) interval.

The safety profiles of the biosimilar and reference products were considered comparable. 

The sponsor proposes identical dosage and dosing regimens for the use of Noromby in the claimed indications as those currently in use by the reference product. 

A scientific rationale, provided to support the authorization of Noromby in the proposed indications held by the reference product Lovenox, was considered in accordance with Health Canadas biosimilar guidance document and is satisfactory.

The final decision for Noromby was based on comparative analytical and functional, non-clinical and pharmacodynamic (PD) comparisons in healthy volunteers. 

Therefore, the benefit/risk balance for Noromby is considered favourable for the treatment and prevention of the thromboembolic disorders as outlined in the approved product monograph and a Notice of Compliance was issued in accordance with the Food and Drug Regulations.