About ZARXIO® (filgrastim-sndz)

Sandoz: A leader in patient access, savings, and manufacturing^1-6

First biosimilar to surpass its reference product in market share⁷

More than 27 million patient-exposure days in 100 countries^7,8
ZARXIO has the most unrestricted combined medical and pharmacy benefit coverage in the SA G-CSF class^9*
Demonstrated cost-effectiveness as primary prophylaxis to decrease the incidence of chemotherapy-induced febrile neutropenia in cancer patients^2,7
Real-world evidence of savings across IDNs, payers, and patients^6,10-12

*"Most" defined as a comparison to Neupogen^®, Granix^®, and Nivestym^® in terms of combined medical and pharmacy benefit status. "Unrestricted" defined as on formulary, managed to Prescribing Information, and not requiring prior authorization and step edits. Coverage defined as "Exclusive or Co-Preferred" on commercial, Medicare, health exchange plans, and pharmacy benefit managers (PBMs) on pharmacy benefit, and commercial, Medicare, and health exchange plans on medical benefit according to Managed Markets Insight & Technology (MMIT) data as of June 2018.⁹

ZARXIO cost savings may liberate healthcare resources and expand patient access

~$1.6 billion savings were driven by biosimilar filgrastim^2†

Cost savings chart

Biosimilars allow for expanded patient access and significant savings for patients, helping alleviate the overburdened healthcare system²

Sandoz is committed to bringing biosimilars to more patients around the world

Strong investment in manufacturing: End-to-end technical capabilities ensure the reliable development, manufacturing, and supply of industry-leading, quality biosimilars
Robust pipeline: With 8 approved biosimilars in Europe, as well as a strong development pipeline, Sandoz will continue to leverage its global expertise in the US¹³
Proven track record: First company to bring biosimilars to patients in both the US and worldwide^1,14

Learn about Ziextenzo (pegfilgrastim-bmez), the long-acting G-CSF treatment option from Sandoz¹⁵

Visit Ziextenzo.com

G-CSF=granulocyte colony-stimulating factor; IDN=integrated delivery network; SA=short-acting.

Neupogen is a registered trademark of Amgen Inc.
Granix is a registered trademark of Teva Pharmaceutical Industries Ltd.
Nivestym is a registered trademark of Pfizer Inc.

References: 1. FDA approves first biosimilar product Zarxio [press release]. US Food and Drug Administration; March 6, 2015. http://web.archive.org/web/20180126055225/https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm436648.htm. Accessed January 13, 2021. 2. Data on file. Filgrastim Net Sales Analysis Model. Sandoz Inc. April 2021. 3. Wang W, Campbell K, Balu S. Cost-minimization analysis for biosimilar pegfilgrastim in the prophylaxis of chemotherapy induced (febrile) neutropenia and expanded access based on budget neutral basis. J Clin Oncol. 2019;37(suppl 15):6645. doi:10.1200/JCO.2019.37.15_suppl.6645. 4. US Food and Drug Administration. Presented at: FDA Oncologic Drugs Advisory Committee Meeting; January 7, 2015. 5. Data on file. Novartis Manufacturing Manual Version 2.0. Sandoz Inc. 6. Puckrein G, Xu Liu, Ryan A, Campbell K, Balu S. Potential Medicare beneficiary out-of-pocket reductions through using biosimilar filgrastim-sndz over reference filgrastim: a simulation analysis. Poster presented at: AMCP Nexus; October 22–25, 2018; Orlando, Florida. 7. Data on file. Zarxio and Ziextenzo Market Share Analysis. Sandoz Inc. October 2020. 8. Data on file. Sandoz Biosimilar PSUR Data. Sandoz Inc. February 2021. 9. Data on file. Zitter Raw Data. October 2017. 10. Data on file. Zarxio Sales WAC Pricing. Sandoz Inc. November 2020. 11. Trautman H, Szabo E, James E, Tang B. Patient-administered biologic and biosimilar filgrastim may offer more affordable options for patients with nonmyeloid malignancies receiving chemotherapy in the United States: a budget impact analysis from the payer perspective. J Manag Care Spec Pharm. 2019;25(1):94-101. doi:10.18553/jmcp.2018.18094. 12. Data on file. IDN Qualitative Insights Series Presentation created by Zitter Health Insights. Sandoz Inc. 2018. 13. Columbus G. Pegfilgrastim biosimilar approved in Europe. OncLive website. https://www.onclive.com/web-exclusives/pegfilgrastim-biosimilar-approved-in-europe. Published November 27, 2018. Accessed January 15, 2021. 14. Data on file. Periodic Safety Update Report (PSUR) for somatropin – containing products, April 1, 2017 ⎼ September 30, 2017. Sandoz Inc. November 2017. 15. 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

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.

Please see full Prescribing Information for ZARXIO.

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.

Real-world Experience

Sandoz: A leader in patient access, savings, and manufacturing1-6

First biosimilar to surpass its reference product in market share7