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Authors: Cornelius F. Waller, Gopinath M. Ranganna, Eduardo J. Pennella, Christopher Blakeley, Miguel H. Bronchud, Leonard A. Mattano Jr, Oleksandr Berzoy, Nataliia Voitko, Yaroslav Shparyk, Iryna Lytvyn, Andriy Rusyn, Vasil Popov, István Láng, Katrin Beckmann, Rajiv Sharma, Mark Baczkowski, Mudgal Kothekar & Abhijit Barve

Date: Mar 1st, 2019



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. (, NCT02467868; EudraCT, 2014-002324-27).

Funding: This study was funded by Mylan Inc., Canonsburg, PA, and Biocon Limited, Bangalore, India.

Authors: Sheridan M. Hoy

Date: Jan 30th, 2019



Pegfilgrastim-jmdb/MYL-1401H (FULPHILA™) [hereafter referred to as pegfilgrastim-jmdb] is a biosimilar of the reference pegylated recombinant granulocyte colony-stimulating factor pegfilgrastim. It is approved for use in patients receiving chemotherapy for malignancy to decrease the incidence of infection, as manifested by febrile neutropenia, in the USA and to reduce the duration of neutropenia and the incidence of febrile neutropenia in the EU. Pegfilgrastim-jmdb has similar physicochemical characteristics and functional properties to those of US- and EU-sourced reference pegfilgrastim, and the pharmacodynamic and pharmacokinetic similarity of the agents has also been demonstrated in healthy volunteers. Pegfilgrastim-jmdb demonstrated clinical efficacy equivalent to that of EU-sourced reference pegfilgrastim in patients with newly diagnosed Stage II/III breast cancer receiving neoadjuvant or adjuvant chemotherapy and was generally well tolerated in this patient population. The overall safety profile and immunogenic potential of the two agents was similar. The role of reference pegfilgrastim in the management of chemotherapy-induced neutropenia is well established and pegfilgrastim-jmdb provides an effective biosimilar alternative for patients requiring pegfilgrastim therapy.

Authors: Cornelius F. Waller, Renger G. Tiessen, Tracey E. Lawrence, Andrew Shaw, Mark Shiyao Liu, Rajiv Sharma, Mark Baczkowski, Mudgal A. Kothekar, Catherine E. Micales, Abhijit Barve, Gopinath M. Ranganna & Eduardo J. Pennella

Date: Apr 18th, 2018


Abstract –

Purpose: Pegfilgrastim is a long-acting granulocyte colony-stimulating factor indicated for prevention of febrile neutropenia in patients receiving myelosuppressive chemotherapy by promoting neutrophil recovery.

Methods: This phase 1, randomized, double-blind, three-way crossover trial in healthy volunteers evaluated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of the proposed biosimilar, comparing MYL-1401H, reference pegfilgrastim (Neulasta®, Amgen Inc, Thousand Oaks, CA, USA) sourced from the European Union, and reference pegfilgrastim sourced from the USA. Primary PK end points were peak plasma concentration of pegfilgrastim (Cmax) and area under the plasma concentration–time curve from the time of dosing to infinity (AUC0−inf). Primary PD end points were area under the curve above baseline for absolute neutrophil counts (ANC AUC0−t) and maximum change from baseline for ANC (ANC Cmax). Adverse events were also recorded.

Results: The primary PK and PD end points were similar across all groups. For the PK parameters, the 90% confidence intervals (CIs) of the ratios of geometric means ranged between 0.91 and 1.18, which were within the predefined bioequivalence interval of 0.8000 to 1.2500 for all comparisons. For the PD parameters, the 95% CIs of the ratios of geometric means ranged between 0.94 and 1.06 for all comparisons, which were within the predefined PD equivalence interval of 0.8500 to 1.1765. The safety profiles were similar, with the most common adverse events being back pain and headache.

Conclusions: MYL-1401H demonstrated similar PK, PD, and safety to reference pegfilgrastim in healthy volunteers and may be an equivalent option for the prevention of febrile neutropenia.

Funding: This study was funded by Mylan Inc, Canonsburg, PA, and Biocon Ltd, Bangalore, India.

Authors: C Waller, Gopinath M. Ranganna, Eduardo Pennella, Leonard A. Mattano, MD, Chien Chang Loa, Charles Donnelly, Mark Shiyao Liu, Heather Watson, Julien St-Jean, Sanjukta Chatterjee, Vivek Nayak, Nilanjan Sengupta, Mudgal A. Kothekar, Abhijit Barve

Date: Dec 7th, 2017



Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is indicated for reduction of incidence of febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy. Here, the immunogenicity data for MYL-1401H, a proposed biosimilar of pegfilgrastim, from the clinical studies will be presented.


Authors: Praveen Kallamvalliillam Sankaran, Dinesh V. Palanivelu, Reshmi Nair, Preethy S.E. Nair, Harish V. Pai, Praveen Reddy Moole, Rajesh Ullanat, Parag Goyal, Daniel Ranayhossaini, Jeffrey Smith, Gopinath Ranganna

Date: June 1st, 2018


Abstract –

Background: MYL-1401H is a proposed biosimilar of pegfilgrastim (Neulasta [peg-GCSF]), a long-acting granulocyte colony-stimulating factor (GCSF) indicated for prevention of febrile neutropenia in patients receiving myelosuppressive chemotherapy

Methods: Structural and physicochemical characterization of MYL-1401H and US-licensed and EU-approved peg-GCSF (US- and EU-peg-GCSF) were performed. GCSF receptor binding was assessed by surface plasmon resonance and potency measured by in vitro stimulated proliferation in the murine myelogenous leukemia cell line M-NFS-60. In vivo rodent studies included a pharmacodynamic study (single dose up to 3 mg/kg) using a validated chemically induced neutropenic rat assay and a 28-day repeat-dose toxicology study (up to 1.5 mg/kg/day).

Results:MYL-1401H, US-, and EU-peg-GCSF demonstrated high similarity in structure, molecular mass, impurities, and functional activity. Similar GCSF receptor binding was observed for MYL-1401H, US-, and EU-peg-GCSF: mean (SD) KD, 394 (40), 380 (49), and 397 (51) pM, respectively. Equivalent relative potency was observed in in vitro cell proliferation: mean (SD), 1.05 (0.08), 1.05 (0.05), and 1.01 (0.07). Neutrophil (Table) and leucocyte counts were comparably increased in neutropenic rats. Toxicology findings and drug kinetics were comparable between MYL-1401H and EU-peg-GCSF.

Conclusions: MYL-1401H, US-, and EU-peg-GCSF demonstrated high analytical and functional similarity.