Ziextenzo (pegfilgrastim-bmez) / Sandoz - LARVOL DELTA

Patterns of Medicare Utilization and Spending on Granulocyte Colony-Stimulating Factors: Filgrastim, Pegfilgrastim, and Their Biosimilars (ASH 2024) - "Data for Neupogen and its biosimilars (Zarxio, Nivestym, Granix) and Neulasta and its biosimilars (Fulphila, Udenyca, Ziextenzo and Nyvepria) was extracted. Neulasta maintains the lowest average spending per beneficiary, highlighting its ongoing value proposition despite the increasing role of biosimilars in the treatment landscape. In conclusion, by leveraging the market competition from biosimilars, the healthcare system can achieve a more balanced approach to delivering high-quality care while managing costs effectively."

Medicare • Reimbursement • US reimbursement

Cencora Analysis Shows Differences in Payer Coverage Between G-CSF Biosimilars (Center for Biosimilars) - "According to a study by Cencora, there is a discrepancy in payer coverage for granulocyte colony-stimulating factor (G-CSF) biosimilars. Although filgrastim biosimilars are frequently preferred over the originator (Neupogen), reference pegfilgrastim (Neulasta) continues to hold a dominant position over its biosimilar counterparts....From the analyzed payers, 38 (76%) had policies for filgrastim and 42 (84%) has policies for pegfilgrastim....For filgrastim biosimilars, 32 (84%) payers preferred Zarxio (filgrastim-sndz), which was the first biosimilar approved in the US. Nivestym (filgrastim-aafi) was the second most preferred filgrastim product, with 14 (37%) payers selecting it as the preferred product....Regarding pegfilgrastim biosimilars, 62% (n = 26) of payers preferred Ziextenzo, 60% (n = 25) preferred Neulasta, 55% (n = 23) preferred Fulphila."

Reimbursement • Oncology

Changes in US payer biosimilar coverage policies of granulocyte colony-stimulating factor products (AMCP 2024) - "For filgrastim biosimilars, 84% of payers preferred Zarxio, whereas Neupogen, Nivestym, and Releuko were most commonly nonpreferred...For pegfilgrastim biosimilars, 62% of payers preferred Ziextenzo, 60% preferred Neulasta, and 55% preferred Fulphila, whereas Nyvepria, Fylnetra, and Stimufend were most commonly nonpreferred. Prefer- ence for Udenyca was split, with 45% of payers preferring this agent and 45% of payers listing it as nonpreferred... Payer policies for granulocyte colony stimu- lating factor biosimilars indicated that Neulasta has retained much of its preferred status, whereas Neupogen is often nonpreferred. In both cases, average time to policy addition was about 4 months after FDA approval. Further, pegfil- grastim policies had more updates to the preferred product status than filgrastim policies, possibly because of more pegfilgrastim biosimilars being approved and marketed."

Long-Term Real-World Post-approval Safety Data of Multiple Biosimilars from One Marketing-Authorization Holder After More than 18 Years Since Their First Biosimilar Launch. (PubMed, Drug Saf) - "This is one of the largest reviews of post-approval biosimilar pharmacovigilance data to date by one MAH. The real-world experience of all eight marketed Sandoz biosimilars for up to 18 years demonstrates that Sandoz biosimilars can be used as safely as their respective reference biologics. Therefore, patients and healthcare providers can be confident in the clinical benefit and safety of Sandoz biosimilars. It is reasonable to believe that similar conclusions about safety may be reached for other biosimilars developed and approved to the high standards as are already in place by major health authorities such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The long-term safety of biosimilars demonstrated here provides strong support for the concept of biosimilarity."

Biosimilar launch • Journal • Real-world • Real-world evidence

Cost-effectiveness of granulocyte colony-stimulating factors (G-CSFs) for the prevention of febrile neutropenia (FN) in patients with cancer. (PubMed, Support Care Cancer) - "Biosimilar filgrastim and pegfilgrastim as primary prophylaxis are cost-effective approaches to avoid FN events in patients with BC, NSCLC, or NHL at intermediate risk for FN in Austria, France, and Germany."

Cost effectiveness • HEOR • Journal • Breast Cancer • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Neutropenia • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Effectiveness of biosimilar pegfilgrastim in patients with multiple myeloma after high-dose melphalan and autologous stem cell transplantation. (PubMed, Ann Hematol) - "Novel supportive therapies (e.g., granulocyte colony-stimulating factor) have significantly improved post-ASCT-related mortality; however, data on biosimilar pegfilgrastim-bmez (BIO/PEG) in this setting is lacking. This prospective cohort study compared Italian patients with MM who received BIO/PEG post-ASCT with data collected retrospectively from historical control groups from the same center who received either filgrastim-sndz (BIO/G-CSF) or pegfilgrastim (PEG; originator)...Patients on BIO/PEG had less frequent grade 2-3 diarrhea (5.5%) compared with BIO/G-CSF (22.5%) or PEG (21.9%); grade 2-3 mucositis was most frequent in the BIO/G-CSF group. In conclusion, pegfilgrastim and its biosimilar displayed an advantageous efficacy and safety profile compared with biosimilar filgrastim in patients with MM post-ASCT."

Journal • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Mucositis • Multiple Myeloma • Neutropenia • Oncology • Transplantation

Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer (clinicaltrials.gov) - P3; N=249; Recruiting; Sponsor: National Cancer Institute (NCI); Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD4

Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects (SABCS 2017) - "This study shows similar PK, PD and safety of LA-EP2006 to the reference pegfilgrastim."

Breast Cancer

Biosimilars May Reduce Disparities in Febrile Neutropenia Treatment (Oncology Nursing News) - "'We [now] have several biosimilars available in the US and around the world, [with the reference agents] filgrastim and pegfilgrastim' said Crawford, in a presentation on new and emerging agents on outcomes of febrile neutropenia during the 2022 Supportive Care in Cancer Annual Meeting.'The potential impact of this is significant; [it represents] greater patient access, greater competition between the companies, and fostered innovation.'"

Media quote

A review of the totality of evidence supporting the development and approval of a pegfilgrastim biosimilar (LA-EP2006). (PubMed, Curr Med Res Opin) - "Clinical studies in a sensitive patient population also demonstrated similar efficacy, safety, and immunogenicity between Sandoz biosimilar pegfilgrastim and the reference biologic. The totality of evidence confirms that Sandoz biosimilar pegfilgrastim matches the reference biologic and will therefore provide equivalent efficacy and safety in all eligible indications."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

FDA’s naming rule for biosimilars has undermined Congress and health care (STAT) - "I recently tried to order white blood cell growth factor (pegfilgrastim) biosimilar for one of my patients. This is a drug that helps prevent fever and infection associated with low white blood cell counts. For years, prescribing it has been simple, since the only option was the brand-name drug, Neulasta brand pegfilgrastim....Nevertheless, the FDA now requires all biologics to bear a four-letter suffix in addition to the generic name which would identify it to regulators. There are no data comparing one biosimilar to another, so physicians and pharmacists must assume it works as well as the others....Is it any wonder the advent of biosimilars has not resulted in the anticipated savings to the health care system? This week I was able to finally get pegfilgrastim-cbqv (Udenyca) approved for my patient and covered by the patient’s insurance, but only after multiple phone calls with the insurer. Now I can only hope it will be delivered in time."

Online posting

Meta-analysis of Pharmacokinetic/Pharmacodynamic Results of 3 Phase 1 Studies with Biosimilar Pegfilgrastim. (PubMed, Clin Pharmacol Drug Dev) - "This meta-analysis of 3 phase 1 studies supports PK/PD similarity of Sandoz biosimilar pegfilgrastim to US- and EU-reference pegfilgrastim. No clinically meaningful differences in safety or tolerability were observed."

Journal • P1 data • PK/PD data • Retrospective data • Hematological Disorders • Neutropenia

Sandoz Canada congratulates the Quebec government on implementing a shift towards biosimilars (GlobeNewswire) - "The shift announced by Quebec will follow a similar approach to policies introduced in British Columbia, Alberta and recently in New Brunswick to transition patients who use a reference biologic to a biosimilar. This will contribute to substantial annual savings that can be reinvested in healthcare and innovative new drugs. The transition will take place under the supervision of the attending physicians and patients will continue receiving safe and effective treatment. Sandoz Canada has a portfolio of six biosimilars (Omnitrope, Rixymio, Erelzi, Hyrimoz, Ziextenzo and Inclunox)."

Commercial • Immunology • Oncology

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas (clinicaltrials.gov) - P1; N=54; Not yet recruiting; Sponsor: National Cancer Institute (NCI)

Clinical • New P1 trial • Diffuse Large B Cell Lymphoma • Human Immunodeficiency Virus • Infectious Disease • CD20 • CD4

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas (clinicaltrials.gov) - P1; N=54; Not yet recruiting; Sponsor: National Cancer Institute (NCI); Trial completion date: Sep 2020 ➔ Jul 2023; Trial primary completion date: Sep 2020 ➔ Jul 2023

Clinical • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: National Cancer Institute (NCI); Not yet recruiting ➔ Recruiting; Trial primary completion date: Jul 2023 ➔ Sep 2021

Clinical • Enrollment open • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: National Cancer Institute (NCI); Suspended ➔ Recruiting

Clinical • Enrollment open • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas (clinicaltrials.gov) - P1; N=54; Suspended; Sponsor: National Cancer Institute (NCI); Recruiting ➔ Suspended

Clinical • Trial suspension • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: National Cancer Institute (NCI); Not yet recruiting ➔ Recruiting; Trial primary completion date: May 2019 ➔ Sep 2020

Clinical • Enrollment open • Trial primary completion date • Diffuse Large B Cell Lymphoma • Human Immunodeficiency Virus • Infectious Disease • CD20 • CD4

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Sep 2021 ➔ Sep 2023

Clinical • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4

Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma (clinicaltrials.gov) - P3; N=192; Not yet recruiting; Sponsor: National Cancer Institute (NCI)

Clinical • Combination therapy • New P3 trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of a New Way to Treat Children With a Brain Tumor Called NGGCT (clinicaltrials.gov) - P2; N=160; Not yet recruiting; Sponsor: Children's Oncology Group

Clinical • New P2 trial • Brain Cancer • Embryonal Tumor • Germ Cell Tumors • Oncology • Solid Tumor

[VIRTUAL] Incremental cost-effective ratio (ICER) analysis of pegfilgrastim biosimilars: a pharmacoeconomics study (ASHP 2020) - "These three agents were Ziextenzo®, Fulphila®, and Udenyca®. The ICER was useful because mutual pharmacodynamic outcomes were available in the literature for each of the available products. This allowed for a comparison of agents that were biosimilar but not therapeutically interchangeable since they do not meet any additional requirements compared to Neulasta® and would need to be evaluated in a new study to gain that status. Regardless, defining the two agents in terms of an ICER allows for a quick and easy comparison that can be used to determine the cost effectiveness of FDA approved biosimilars."

HEOR • Hematological Disorders • Neutropenia • Oncology

Biosimilar Drugs and Cancer Treatment-What You Need to Know (Maven Doctors) - "One way to lower the cost of biologic medications is to create biosimilar drugs that have active properties highly similar to an already FDA-approved biological drug. The FDA approved Herzuma a biosimilar to Herceptin and Truxima as the first biosimilar to Rituxan (rituximab) for patients with CD20-positive, B-cell non-Hodgkin’s lymphoma to be used as a single agent or in combination with chemotherapy....Does a patient with an extrapolated disorder wait to choose a biosimilar until a study is published in the United States demonstrating efficacy and safety in their disease? Savings to the patient and society are clearly worthwhile, but only when originator and biosimilar result in the same effectiveness and safety."

Online posting

"Sandoz Canada launches two new biosimilars Ziextenzo and Riximyo @Novartis #sandozcanada #sandoz #sandoznews #ziextenzo #riximyo #pegfilgrastim #neulasta #rituximab #rituxan https://t.co/YBcRDDOepj" (@medicaldialogs)

Biosimilar launch • Launch Canada