Regulatory Decision Summary for Nivestym

Comparable pharmacokinetics/pharmacodynamics (PK/PD) between Nivestym and US Neupogen was established in a single dose comparative PK/PD study and a multiple dose comparable PK/PD study conducted in healthy subjects.

For the single dose study, PK comparability was demonstrated as the ratio of geometric means (GMR) for Cmax and the 90% Confidence Interval (CI) for the AUC0-last were within the equivalence margins of 80.0% to 125.0% for measured (potency uncorrected) data and potency corrected data. PD comparability (absolute neutrophil count (ANC) as the relevant PD marker for the activity of G-CSF) was also demonstrated as the 95% Confidence Interval (CI) for the AUECANC and ANCmax parameters were within the equivalence margins of 80.0% to 125.0%.

For the multiple dose study, PK comparability was demonstrated as the ratio of geometric means (GMR) for Cmax and the 90% Confidence Interval (CI) for the AUC0-24 at Day 5 were within the equivalence margins of 80.0% to 125.0% for measured (potency uncorrected) data and potency corrected data. PD comparability (CD34+ count as the relevant PD marker to support the hematopoietic progenitor cell mobilization indication) was also demonstrated as the 95% Confidence Interval (CI) for the AUECCD34+ and CD34+max parameters were within the equivalence margins of 80.0% to 125.0%.

In addition, in terms of immunogenicity, Nivestym was demonstrated to be non-inferior to US Neupogen in a parallel arm, multiple dose non-inferiority study conducted in healthy volunteers. The U.S.-sourced reference product (US Neupogen) was used as a suitable proxy for the Canadian reference product in the clinical studies.

The safety profile of Nivestym is generally consistent with the known safety profile of Neupogen. No new safety signals were observed in healthy volunteers from the submitted clinical studies. The known risks of Neupogen have been included in the Product Monograph (PM) for Nivestym. The Contraindications, Serious Warnings and Precautions box, Warnings and Precautions, and Adverse Reactions sections from Neupogen are retained in the PM for Nivestym.

Like other biologics, the clinical safety of Nivestym should be monitored closely on an ongoing basis during the post-approval phase including continued risk-benefit assessment. Post-marketing pharmacovigilance data will be critical to ensure patient safety with respect to the duration of exposure, use in various populations, rare adverse events, immunogenicity and other treatment issues that might emerge post approval.

The final decision for this product was based on the totality of evidence, including structural, functional, non-clinical, PK/PD and clinical comparisons. Furthermore, the scientific rationale provided by the Sponsor to support the authorization of Nivestym in other indications held by the reference biologic drug is considered adequate and is in line with Health Canadas biosimilar guidance document. Therefore, the benefit-risk profile of Nivestym is considered favourable for the indications, doses and routes of administration for which the Canadian reference product, Neupogen, are licensed and are recommended to be granted to Nivestym.

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