1433O - Phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H vs EU-neulasta® in the prophylaxis of chemotherapy-induced neutrop...

Date 08 October 2016
Event ESMO 2016 Congress
Session Supportive and palliative care
Topics Supportive Measures
Presenter Cornelius Waller
Citation Annals of Oncology (2016) 27 (6): 497-521. 10.1093/annonc/mdw390
Authors C.F. Waller1, C. Blakeley2, E. Pennella3, M. Bronchud4, O. Berzoy5, N. Voitko6, H. Adamchuk7, Z. Zautashvili8, Y. Vinnyk9, G. Nemsadze10, G. Dzagnidze11, Y. Shparyk12, I. Lytvyn13, A. Rusyn14, V. Popov15, I. Lang16, R. Sharma17, M. Baczkowski18, M. Kothekar19, A. Barve3
  • 1Department Of Haematology, Oncology And Stem Cell Transplantation, University Medical Centre Freiburg And Faculty Of Medicine, University of Freiburg, Freiburg, D-79106 - Freiburg/DE
  • 2Medical And Scientific Affairs, Worldwide Clinical Trials, W1T 7NS - London/GB
  • 3Global Clinical Research, Mylan, 15317 - Canonsburg/US
  • 4Clinical Oncology, Instituto Universitario USP Dexeus, 08028 - Barcelona/ES
  • 5Mammology Center, Odessa Regional Hospital, 65025 - Odessa/UA
  • 6Chemotherapy Ii, Kyiv City Clinical Oncological Centre, 03115 - Kiev/UA
  • 7Chemotherapy, Kryviyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council, 5004 - Kryvyi Rih/UA
  • 8Research Institute Of Clinical Medicine, Research Institute of Clinical Medicine, 0112 - Tbilisi/GE
  • 9Department Of General Oncology Surgery #2, Municipal Institution of Healthcare “C”, 61070 - Kharkiv/UA
  • 10Mammological Center, Konstantine Madichi Mammalogy Center, 0159 - Tbilisi/GE
  • 11Breast Unit, S.Khechinashvili Hospital, 0179 - Tbilisi/GE
  • 12Department Of Chemotherapy, Lviv State Regional Treatment and Diagnostics Oncology Center, 79031 - Lviv/UA
  • 13Department Of Chemotherapy, Dnipropetrovsk Regional Clinical Oncology Center, 49100 - Dnepropetrovsk/UA
  • 14Department Of Chemotherapy, Transkarpathian Regional University Oncology Clinic, 88014 - Uzhgorod/UA
  • 15Department Of Medical Oncology And Palliative Care, SHATOD Dr. Marko Аntonov Markov - Varna EOOD, - - Varna/BG
  • 16Dept. Med. Oncology And Clin. Pharmacology B, National Institute of Oncology, 1122 - Budapest/HU
  • 17Global Product Safety And Risk Management, Mylan, AL10 9UL - Hatfield/GB
  • 18Product Safety And Risk Management, Mylan, 26505 - Morgantown/US
  • 19Clinical Research, Biocon Research Limited, 560099 - Bangalore/IN



MYL-1401H is a proposed pegfilgrastim biosimilar to the reference product EU-Neulasta®, based on physicochemical characterization, in vitro bioassays, toxicokinetics (TK), pharmacokinetics (PK), and pharmacodynamics (PD) studies.


This is a phase 3, multicenter, randomized, double-blind, parallel-group trial of MYL-1401H vs EU-Neulasta®. Chemotherapy and radiotherapy naïve patients with newly diagnosed Stage II/III breast cancer were eligible to receive docetaxel, doxorubicin, and cyclophosphamide anti-cancer chemotherapy planned every 3 weeks for 6 chemotherapy cycles. A total of 194 patients were randomized in a 2:1 ratio to receive 6 mg/0.6 mL of either MYL-1401H or EU-Neulasta® on Day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia (DSN) in Cycle 1, defined as days with absolute neutrophil count (ANC) 


The mean ± SD DSN in the MYL-1401H and EU-Neulasta® groups were 1.2 ± 0.93 and 1.2 ± 1.10, respectively. The 95% CI of least squares means difference [-0.285 day, 0.298 day] was within [-1 day, +1 day] range, that was also corroborated by the sensitivity analysis. Other endpoints of the study including Grade 3-4 neutropenia, time to ANC nadir, and duration of post-nadir recovery were comparable too. The overall safety profile of MYL-1401H was similar to EU-Neulasta® with bone pain, an expected AE, as the most frequently reported treatment related TEAE.


MYL-1401H demonstrated equivalent efficacy to EU-Neulasta® in the prophylaxis of chemotherapy induced neutropenia in patients with breast cancer. MYL-1401H was generally well tolerated and there were no particular safety concerns identified with overall safety profile being similar to EU-Neulasta®.

Clinical trial identification

EudraCT Number: 2014-002324-27

Legal entity responsible for the study

Mylan GmbH


Mylan GmbH


C.F. Waller: Member of advisory board of Mylan. E. Pennella: Mylan Employee and stocks of Mylan. M. Bronchud: Member of consultant/advisory board of Mylan. R. Sharma: Currently employed by Mylan on full term permanent basis and also Mylan stock ownership. M. Baczkowski: Currently an employee of Mylan. In addition, financial relationship with employer in the form of stock options, restricted stock units, and shares of Mylan in retirement account. M. Kothekar: Full-time employee of Biocon Research Limited. A. Barve: Mylan full-time employee and stock in Mylan. All other authors have declared no conflicts of interest.