It looks like you are using an older version of Internet Explorer which is not supported. We advise that you update your browser to the latest version of Microsoft Edge, or consider using other browsers such as Chrome, Firefox or Safari.

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

pioneer study design, showing primary endpoint data for Cycle 1 and Cycle 2 through 6 between ZARXIO and NEUPOGEN®

Back to top

Efficacy

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.

Back to top

Safety

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.

ADVERSE REACTIONS

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. 

CONTRAINDICATIONS

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

WARNINGS AND PRECAUTIONS

  • 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.

USE IN SPECIFIC POPULATIONS

  • 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

Back to top

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

Visit Ziextenzo.com

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.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ZARXIO® (filgrastim-sndz) is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim or pegfilgrastim products.

WARNINGS AND PRECAUTIONS

  • Splenic rupture, including fatal cases, has been reported following the administration of filgrastim products. Patients who report left upper abdominal or shoulder pain should be evaluated.
  • Acute respiratory distress syndrome (ARDS) has been reported in patients receiving filgrastim products. Patients who develop fever and lung infiltrates or respiratory distress should be evaluated. Discontinue ZARXIO in patients with ARDS.
  • Serious allergic reactions, including anaphylaxis, have been reported in patients receiving filgrastim products. The majority of reported events occurred upon initial exposure. Provide symptomatic treatment for allergic reactions. Allergic reactions, including anaphylaxis, in patients receiving filgrastim products can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue ZARXIO in patients with serious allergic reactions.
  • Sickle cell crisis, in some cases fatal, has been reported with the use of filgrastim products in patients with sickle cell trait or sickle cell disease. Discontinue ZARXIO if sickle cell crisis occurs.
  • Glomerulonephritis has occurred in patients receiving filgrastim products. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose reduction or discontinuation of filgrastim products. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of ZARXIO.
  • Alveolar hemorrhage manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization have been reported in healthy donors treated with filgrastim products undergoing peripheral blood progenitor cell (PBPC) collection mobilization. Hemoptysis resolved with discontinuation of filgrastim. The use of ZARXIO for PBPC mobilization in healthy donors is not an approved indication.
  • Capillary leak syndrome (CLS) has been reported after G-CSF administration, including filgrastim products, and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive appropriate treatment.
  • Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukememia (AML):
    • Patients with Severe Chronic Neutropenia: Confirm the diagnosis of severe chronic neutropenia (SCN) before initiating ZARXIO therapy. Myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have been reported to occur in the natural history of congenital neutropenia without cytokine therapy. Cytogenetic abnormalities, transformation to MDS, and AML have also been observed in patients treated with filgrastim products for SCN. Abnormal cytogenetics and MDS have been associated with the eventual development of myeloid leukemia. The effect of filgrastim products on the development of abnormal cytogenetics and the effect of continued filgrastim administration in patients with abnormal cytogenetics or MDS are unknown. Monitor patients for signs and symptoms of MDS/AML in these settings. If a patient with SCN develops abnormal cytogenetics or myelodysplasia‚ the risks and benefits of continuing ZARXIO should be carefully considered.
    • Patients with Breast and Lung Cancer:
      MDS and AML have been associated with the use of filgrastim in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for signs and symptoms of MDS/AML in these settings.
  • Thrombocytopenia has been reported in patients receiving filgrastim products. Monitor platelet counts.
  • Leukocytosis:
    • Patients with Cancer Receiving Myelosuppressive Chemotherapy: White blood cell counts of 100‚000/mm3 or greater were observed in approximately 2% of patients receiving filgrastim at dosages above 5 mcg/kg/day. In patients with cancer receiving ZARXIO as an adjunct to myelosuppressive chemotherapy‚ to avoid the potential risks of excessive leukocytosis‚ it is recommended that ZARXIO therapy be discontinued if the ANC surpasses 10‚000/mm3 after the chemotherapy-induced ANC nadir has occurred. Monitor CBCs at least twice weekly during therapy.
    • Peripheral Blood Progenitor Cell (PBPC) Collection and Therapy: During the period of administration of ZARXIO for PBPC mobilization in patients with cancer, discontinue ZARXIO if the leukocyte count rises to >100,000/mm3.
  • Cutaneous vasculitis has been reported in patients treated with filgrastim products. In most cases‚ the severity of cutaneous vasculitis was moderate or severe. Most of the reports involved patients with SCN receiving long-term filgrastim therapy. Hold ZARXIO therapy in patients with cutaneous vasculitis. ZARXIO may be started at a reduced dose when the symptoms resolve and the ANC has decreased.
  • The possibility that ZARXIO acts as a growth factor for any tumor type cannot be excluded. The safety of filgrastim products in chronic myeloid leukemia (CML) and myelodysplasia has not been established. When ZARXIO is used to mobilize PBPC‚ tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. Available data is limited and inconclusive.
  • The safety and efficacy of ZARXIO given simultaneously with cytotoxic chemotherapy have not been established. Do not use ZARXIO in the period 24 hours before through 24 hours after the administration of cytotoxic chemotherapy. The safety and efficacy of ZARXIO have not been evaluated in patients receiving concurrent radiation therapy. Avoid the simultaneous use of ZARXIO with chemotherapy and radiation therapy.
  • Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging changes on nuclear imaging.
  • Aortitis has been reported in patients receiving filgrastim products. It may occur as early as the first week after start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count). Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue ZARXIO if aortitis is suspected.

ADVERSE REACTIONS

Most common adverse reactions in patients:

  • With nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs (≥ 5% difference in incidence compared to placebo) are thrombocytopenia, nausea, pyrexia, chest pain, pain, fatigue, back pain, arthralgia, bone pain, pain in extremity, dizziness, cough, dyspnea, rash, blood lactate dehydrogenase increased and blood alkaline phosphatase increased
  • With AML (≥ 2% difference in incidence) are epistaxis, back pain, pain in extremity, erythema, and rash maculo-papular
  • With nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT (≥ 5% difference in incidence) are rash and hypersensitivity
  • Undergoing peripheral blood progenitor cell mobilization and collection (≥ 5% incidence) are bone pain, pyrexia, blood alkaline phosphatase increased and headache
  • With severe chronic neutropenia (SCN) (≥ 5% difference in incidence) are arthralgia, bone pain, back pain, muscle spasms, musculoskeletal pain, pain in extremity, splenomegaly, anemia, upper respiratory tract infection, urinary tract infection, epistaxis, chest pain, diarrhea, hypoesthesia, and alopecia

Please see full Prescribing Information for ZARXIO.

INDICATIONS

  • Patients with Cancer Receiving Myelosuppressive Chemotherapy: to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever.
  • Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy: to reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML).
  • Patients with Cancer Undergoing Bone Marrow Transplantation: to reduce the duration of neutropenia and neutropenia-related clinical sequelae, e.g., febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation.
  • Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy: for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.
  • Patients with Severe Chronic Neutropenia: for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g., fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Sandoz Logo

ZARXIO, ZIEXTENZO, and the Sandoz One Source logo are registered trademarks of Novartis AG.
© 2023 Sandoz Inc. 100 College Road West, Princeton, NJ 08540. All Rights Reserved.
255148-1 06/2023