Regulatory Decision Summary for Ziextenzo

To support similarity in the clinical setting, the sponsor provided evidence of comparable pharmacokinetic and pharmacodynamic activity of Ziextenzo to the reference product, Neulasta, in a healthy subject three-period crossover study. The ratios (test/reference) of the geometric means for C_max and AUC_0-last and the 90% confidence interval for the ratio of AUC_0-last were within the pre-defined acceptance range of 80 - 125% as a measure of pharmacokinetic similarity between Ziextenzo and Neulasta. Pharmacodynamic comparisons were determined by calculating the area under the effect curve for absolute neutrophil counts from time zero measured up to the last sampling time (AUEC_0-last), as well as the maximum effect concentration (E_max). The ratios (test/reference) of the geometric means for AUEC_0-last and E_max and the 95% confidence interval for the ratio of AUEC_0-last were within the pre-defined acceptance range of 80 - 125% as a measure of pharmacodynamic similarity.

The safety and immunogenicity comparisons of Ziextenzo to Neulasta were assessed in healthy subjects and in randomized, assessor blinded, active controlled studies in patients with early breast cancer receiving TAC (docetaxel, doxorubicin, cyclophosphamide) anticancer chemotherapy in the neoadjuvant setting. No clinically meaningful differences in safety and immunogenicity between Ziextenzo and Neulasta were observed. On the basis of these results, and considering the similarity demonstrated in comparative structural, functional, and non-clinical studies, the totality of data supports the authorization of Ziextenzo for the same indication as Neulasta.

As the evidence demonstrated similarity of Ziextenzo to Neulasta, the benefit/risk assessment for Ziextenzo is considered positive. A Notice of Compliance was recommended.