Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia

Abstract

Pegfilgrastim is indicated for reducing the duration of neutropenia and incidence of febrile neutropenia in patients receiving cytotoxic chemotherapy. Here, safety and efficacy of MYL-1401H, a proposed pegfilgrastim biosimilar, were investigated as prophylaxis for chemotherapy-induced neutropenia. This was a phase 3, multicenter, randomized, double-blind, parallel-group equivalence trial of MYL-1401H vs European Union-sourced reference pegfilgrastim. Patients with newly diagnosed stage II/III breast cancer eligible to receive (neo) adjuvant chemotherapy with docetaxel/doxorubicin/cyclophosphamide every 3 weeks for 6 cycles were enrolled and randomized 2:1 to 6 mg of MYL-1401H or reference pegfilgrastim 24 h (+ 2-h window after the first 24 h) after the end of chemotherapy. The primary efficacy endpoint was the duration of severe neutropenia in cycle 1 (i.e., days with absolute neutrophil count (ANC) < 0.5 × 109/L). Mean (standard deviation (SD)) duration of severe neutropenia in MYL-1401H and reference pegfilgrastim groups was 1.2 days (0.93) and 1.2 days (1.10), respectively. The 95% CI for least squares mean difference (- 0.285, 0.298) was within the predefined equivalence range of ± 1 day. Secondary endpoints, including grade ≥ 3 neutropenia (frequency, 91% and 82% for MYL-1401H and reference pegfilgrastim, respectively), time to ANC nadir (mean (SD), 6.2 (0.98) and 6.3 (1.57) days), and duration of post-nadir recovery (mean (SD), 1.9 (0.85) and 1.7 (0.91) days) were comparable. Overall safety profiles of the study drugs were comparable. MYL-1401H demonstrated equivalent efficacy and similar safety to reference pegfilgrastim and may be an equivalent option for reducing incidence of neutropenia. ( ClinicalTrials.gov , NCT02467868; EudraCT, 2014-002324-27).

Keywords: Biosimilar; Chemotherapy-induced neutropenia; Febrile neutropenia; Pegfilgrastim.

Conflict of interest statement

Conflict of interest

CF Waller and MH Bronchud are consultants/advisory board members for Mylan. GM Ranganna, EJ Pennella, K Beckmann, M Baczkowski, and A Barve are paid employees of Mylan and may hold stock with the company. C Blakeley is a paid employee of Worldwide Clinical Trials. LA Mattano Jr. has served as a consultant for Alexion, Mylan, Novartis, and Pfizer and may hold stock with Pfizer. R Sharma was a paid employee of Mylan at the time of analysis and may hold stock with the company. M Kothekar is a paid employee of Biocon Research Ltd. and may hold stock with the company. All remaining authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Statement of informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1

Mean ANC over time by treatment in cycle 1 (PP population). ANC absolute neutrophil count, PP per protocol