Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2018 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Characterization and similarity assessment of a pegfilgrastim biosimilar MYL-1401H.
Myelodysplastic Syndromes (MDS)
Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr e19028)
Author(s): 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; Biocon Research Limited, Bangalore, India; Mylan Pharmaceuticals private Limited, Hyderabad, India; Mylan Pharmaceuticals Private Limited, Hyderabad, India; Mylan Inc, Canonsburg, PA; Mylan Inc., Canonsburg, PA
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.
|Dose (mg/kg)||Emax, cells × 109/L blood||tmax, h||AUEC0-t last,|
|AUECeff 0-t last,|
ANC, absolute neutrophil count; AUEC, area under effect-time curve; AUECeff, effective AUEC; Emax, maximum ANC response; tmax, time of Emax.
Mean values are shown. N = 10/group.
1. Association of early intervention in transfusion independent (TI) patients (Pts) with lower-risk myelodysplastic syndromes (MDS) treated with attenuated doses of hypomethylating agents (HMAs) with high response rates and long duration of response.
Meeting: 2018 ASCO Annual Meeting Abstract No: 7001 First Author: Mahesh Swaminathan
Meeting: 2018 ASCO Annual Meeting Abstract No: 7018 First Author: Uwe Platzbecker
Meeting: 2018 ASCO Annual Meeting Abstract No: 7064 First Author: Paolo Strati