Development of a new G-CSF product based on biosimilarity assessment.
BACKGROUND
Zarzio, a new recombinant human granulocyte colony-stimulating factor (filgrastim), was evaluated in healthy volunteers and neutropenic patients in phase I and III studies.


METHODS
Healthy volunteers in randomized, two-period crossover studies received single- and multiple-dose s.c. injections of 1 microg/kg (n = 24), 2.5 microg/kg (n = 28), 5 microg/kg (n = 28), or 10 microg/kg (n = 40), as well as single-dose i.v. infusions of 5 microg/kg (n = 26), of Zarzio or the reference product (Neupogen). Filgrastim serum levels were monitored; pharmacodynamic parameters were absolute neutrophil count (all studies) and CD34(+) cells (multiple-dose studies). Supportive efficacy and safety data were obtained from an open phase III study in 170 breast cancer patients undergoing four cycles of doxorubicin and docetaxel (Taxotere) chemotherapy, receiving Zarzio (300 or 480 microg) as primary prophylaxis of severe neutropenia.


RESULTS
The results of the studies in healthy volunteers confirm the comparability of the test and reference products with respect to their pharmacodynamics and pharmacokinetics. Confidence intervals were within the predefined equivalence boundaries. In the phase III study in breast cancer patients, the administration of Zarzio was efficacious and safe, triggering no immunogenicity.


CONCLUSIONS
The results of these studies demonstrate the biosimilarity of Zarzio with its reference product Neupogen.
Gascon
P
P
Division of Medical Oncology, Hospital Clinic, Barcelona University, Barcelona, Spain.
Fuhr
U
U
Department of Pharmacology, University Hospital, University of Cologne, Cologne, Germany; Itecra GmbH & Co. KG, Cologne, Germany.
Sörgel
F
F
IBMP - Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany; Department of Pharmacology, University of Duisburg-Essen, Essen, Germany.
Kinzig-Schippers
M
M
IBMP - Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany.
Makhson
A
A
Moscow City Oncology Hospital, Moscow, Russia.
Balser
S
S
Sandoz International GmbH, Holzkirchen, Germany.
Einmahl
S
S
Triskel Integrated Services, Geneva, Switzerland.
Muenzberg
M
M
Sandoz International GmbH, Holzkirchen, Germany. Electronic address: michael.muenzberg@sandoz.com.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018592:Cross-Over Studies; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy*; D011994:Recombinant Proteins; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D004317:Doxorubicin; D000069585:Filgrastim