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Confirmed biosimilarity of ZARXIO to NEUPOGEN® (filgrastim)1,2

Biosimilarity was confirmed by the PIONEER study and a PK/PD study that demonstrated equivalence with regard to ANC and CD34+ cell counts1,2

PIONEER was a randomized, double-blind, comparative study of efficacy and safety between ZARXIO and NEUPOGEN® in 218 breast cancer patients treated with myelosuppressive chemotherapy.2*

  • Study duration: 24 weeks1
  • All patients received 6 cycles (3 weeks per cycle) of TAC combination chemotherapy administered on Day 1 of each cycle2
    • Starting on Day 2 of each chemotherapy cycle, ZARXIO or NEUPOGEN® was administered daily and continued until the ANC recovered to 10 x 109/L after the nadir or up to a maximum of 14 days (whichever occurred first)2
  • The study included 4 arms in total2
    • 2 arms received treatment with either ZARXIO or NEUPOGEN® across all cycles
    • 2 arms started with either ZARXIO or NEUPOGEN® in Cycle 1, then alternated treatment in each subsequent cycle

*A total of 218 patients were randomized in the study of which 204 were included in the PP population for the primary analysis. A total of 34 patients did not complete the study as planned or discontinued study treatment prematurely. The PP patients were on average 49.0 years old with an overall range between 23 and 76 years. The median duration since breast cancer diagnosis was 2.0 months (range from 0 to 171 months) and the majority of patients had stage II cancer (51.4%) or stage III cancer (41.6%). A total of 163 patients (76.2%) had an ECOG status of 0 and 51 patients (23.8%) had an ECOG status of 1.3
TAC combination chemotherapy includes docetaxel, doxorubicin, and cyclophosphamide.2

ANC=absolute neutrophil count; CD=cluster of differentiation; ECOG=Eastern Cooperative Oncology Group; PD=pharmacodynamics; PK=pharmacokinetics; PP=primary prophylaxis.

Study Design


Primary endpoint for equivalence (in Cycle 1): mean DSN2,4a

primary endpoint design data and DSN difference information between ZARXIO and NEUPOGEN®

aDefined as the number of consecutive days with severe neutropenia (ANC less than 0.5 x 109/L) in Cycle 1.2
bANCOVA with treatment, disease status, and baseline ANC level4

Biosimilarity demonstrated through the totality of evidence3

secondary endpoints Cycle 1 biosimilarity data between ZARXIO and NEUPOGEN®


aSecondary endpoints were not adjusted for multiplicity.3
bDefined as oral temperature ≥38.3°C while having an ANC <0.5 x 109/L (both measured on the same day).3
cANC recovery was defined as the time in days from ANC nadir until the patient's ANC increases to ≥2 x 109/L after the nadir in Cycle 1.3
dDefined as the patient's lowest ANC in Cycle 1.3
eDefined as oral temperature ≥38.3°C.3

ANC profiles of ZARXIO and NEUPOGEN®2

secondary endpoint chart showing the depth of absolute neutrophil count nadir in Cycle 1, comparing ZARXIO and NEUPOGEN®

aThe nadir occurred around Days 7 and 8. There were no marked differences in the mean ANC between ZARXIO and NEUPOGEN® up to Day 10.2

No antibodies against rhG-CSF

ANCOVA=analysis of variance; DSN=duration of severe neutropenia; FN=febrile neutropenia; rhG-CSF=recombinant human granulocyte colony-stimulating factor.

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Cardinal adverse events (between-group comparison)4

cycle 1 by treatment chart, comparing ZARXIO and NEUPOGEN® musculoskeletal pain and injection site reaction

aIncludes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, pain, pain in extremity, or spinal pain.
bIncludes injection site erythema, extravasation, hematoma, pain, or pruritus.

treatment emergent adverse events data showing differences in side effects between ZARXIO and NEUPOGEN®

The overall safety profile of ZARXIO was similar across all 6 cycles with continuous treatment.3

Prescribing Information adverse reactions

The following most common adverse reactions listed in the ZARXIO Prescribing Information are based on the reference biologic.


Most common adverse reactions in patients:

  • With nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs (≥ 5% difference in incidence compared to placebo) are pyrexia, pain, rash, cough, and dyspnea
  • With AML (≥ 2% difference in incidence) are pain, epistaxis and rash
  • With nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT (≥ 5% difference in incidence) is rash
  • Undergoing peripheral blood progenitor cell mobilization and collection (≥ 5% incidence) are bone pain, pyrexia and headache
  • With severe chronic neutropenia (SCN) (≥ 5% difference in incidence) are pain, anemia, epistaxis, diarrhea, hypoesthesia and alopecia

    *Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of ZARXIO has been demonstrated for the condition(s) of use (e.g. indication(s), dosing regimen(s), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information. 


  • Patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim or pegfilgrastim products


  • Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture
  • Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS. Discontinue ZARXIO in patients with ARDS
  • Serious allergic reactions, including anaphylaxis: Permanently discontinue ZARXIO in patients with serious allergic reactions
  • Fatal sickle cell crises: Discontinue ZARXIO if sickle cell crisis occurs
  • Glomerulonephritis: Evaluate and consider dose-reduction or interruption of ZARXIO if causality is likely
  • Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML): Monitor patients with breast and lung cancer using ZARXIO in conjunction with chemotherapy and/or radiotherapy for signs and symptoms of MDS/AML
  • Thrombocytopenia: Monitor platelet counts.


  • ZARXIO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
  • There is published literature documenting transfer of filgrastim into human milk

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Learn about ZIEXTENZO (pegfilgrastim-bmez), the long-acting G-CSF treatment option from Sandoz5

NEUPOGEN is a registered trademark of Amgen Inc.

References: 1. Data on file. Summary of clinical efficacy: EP2006 (INN: filgrastim) 300 mcg/0.5 mL and 480 mcg/0.8 mL solution for injection. Sandoz Inc. February 2014. 2. Blackwell K, Semiglazov V, Krasnozhon D, et al. Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. Ann Oncol. 2015;26(9):1948-1953. 3. Data on file. Clinical Study Report of study EP06-302 (PIONEER): a randomized double-blind, parallel-group, multi-center Phase III study comparing the efficacy and safety of EP2006 and Neupogen® in breast cancer patients treated with myelosuppressive chemotherapy. Sandoz Inc. December 2013. 4. US Food and Drug Administration. Overview of the Regulatory Pathway and FDA’s Guidance for the Development and Approval of Biosimilar Products in the US. 5. ZIEXTENZO Prescribing Information. Sandoz Inc. March 2021.