Demonstration of Clinical Comparability of the Biosimilar Filgrastim to Neupogen, in Terms of Safety and Efficacy, in Healthy Volunteers and Patients Receiving Myelosuppressive Chemotherapy

Aim: To demonstrate biosimilarity as evidenced by the pharmacokinetic (PK), pharmacodynamics (PD), efficacy and safety comparability of Accofil ® /Grastofil ® (filgrastim), a recombinant human granulocyte colony-stimulating factor, and the reference product, Neupogen ® . Patients and methods: Four phase I studies were conducted to demonstrate the comparative efficacy of Accofil/Grastofil and Neupogen. PD and PK parameters of Accofil/Grastofil (filgrastim) at and around the main clinical dose (5 μg/kg), using both the intravenous (IV) and subcutaneous (SC) routes of administration, were compared with Neupogen (EU) in healthy volunteers in three phase I clinical studies in a single-dose setting and following multiple-dose administration. An additional phase I PK/PD study was performed to compare Accofil/ Grastofil (filgrastim) to both EU-approved Neupogen and US-licensed Neupogen following the administration of a fixed SC dose of 300 μg. The efficacy and safety of Accofil/Grastofil was also evaluated in chemotherapy-naive women with stage IIA, IIB and IIIA breast cancer receiving docetaxel, doxorubicin, cyclophosphamide (TAC) chemotherapy. No comparator arm was included in this study so the efficacy and safety comparison was made with published data for the reference product, Neupogen. Results: A total of 235 healthy subjects were enrolled in the phase I studies and 120 patients in the phase III study. The PK and PD data demonstrated high comparability of the Accofil/ Grastofil and Neupogen products, with the 90 % confidence interval (CI) for primary PK parameters and 95 % CI for primary PD parameters falling within the pre-defined equivalence limits. In the phase III study, Accofil/Grastofil (filgrastim) demonstrated a safety and efficacy profile that was similar to the published data for the reference product Neupogen for the reduction of the duration of neutropenia in patients with breast cancer who were undergoing chemotherapy. Conclusion: Lack of clinically meaningful differences was convincingly demonstrated between Accofil/Grastofil (filgrastim) and the reference product, Neupogen.