Nivestym (filgrastim-aafi) / Pfizer - 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 • Hematological Disorders

Real-World Noninferiority Assessment of Two Filgrastim Biosimilars in Patients Receiving Myelosuppressive Chemotherapy. (PubMed, JCO Oncol Pract) - "Among patients with select solid tumors receiving myelosuppressive chemotherapy, severe neutropenia outcomes were comparable between filgrastim-aafi and filgrastim-sndz biosimilars. Findings from this study may support utilization of different filgrastim biosimilars in clinical practice."

Head-to-Head • Journal • Real-world • Real-world evidence • Breast Cancer • Febrile Neutropenia • Hematological Disorders • Neutropenia • Oncology • Solid Tumor

Industry perspective on regulatory authority (RA) quality reviews of biosimilar applications - an evaluation of RA guidance and expectations for chemical, manufacturing, and controls information through in-depth query analysis. (PubMed, Expert Opin Biol Ther) - "Numbers/types of queries received following regulatory submissions (FDA/EMA, n = 7/n = 5) for seven biosimilars (PF-filgrastim [Nivestym], PF-rituximab [Ruxience®], PF-trastuzumab [Trazimera®], PF-bevacizumab [Zirabev®], PF-pegfilgrastim [Nyvepria®], PF-adalimumab [Abrilada™/Amsparity®], PF-infliximab [Ixifi]) from a single product portfolio were analyzed considering published regulatory authority (RA) guidance and in relation to sections/subsections of Module 3: Quality from the Common Technical Document regulatory dossier and topics based on keyword assignment. Topic assignments included: Control (12-27%/12-28%), Manufacturing (56-72%/34-66%), Stability (1-12%/2-24%), Biosimilarity (5-16%/5-25%), and Container Closure (0-3%/0-9%). The focus of both RAs on topics related to manufacturing and controls is valuable in understanding expectations for scientific and technical content related to gaining biosimilar approval."

Journal

Comparison of biosimilar filgrastim and originator filgrastim for peripheral blood stem cell mobilization for allogeneic hematopoietic stem cell transplantation. (PubMed, Transfusion) - "Nivestym demonstrated similar efficacy for PBSC mobilization compared with Neupogen among allo-HSCT donors. In donors aged 35 years or younger, a slightly lower PBSC product CD34+ count was noted with Nivestym compared with Neupogen."

Journal • Bone Marrow Transplantation • Transplantation

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."

Comparison of Biosimilar Filgrastim (Nivestym) Versus Originator Filgrastim (Neupogen) for Peripheral Blood Stem Cell Mobilization for Allogeneic Hematopoietic Stem Cell Transplantation (TCT-ASTCT-CIBMTR 2024) - "Biosimilar G-CSF (Nivestym) demonstrated similar efficacy for peripheral blood stem cell mobilization compared to the originator G-CSF (Neupogen) among allogeneic HSCT donors. In donors aged 35 years or younger, a slightly lower PBSC product CD34 count was noted with Nivestym compared to Neupogen."

Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Oncology • Transplantation

Comparison of Biosimilar Filgrastim (Nivestym) Versus Originator Filgrastim (Neupogen) for Peripheral Blood Stem Cell Mobilization for Allogeneic Hematopoietic Stem Cell Transplantation (ASH 2023) - "Nivestym, a biosimilar G-CSF to the originator Filgrastim (Neupogen), is now used by multiple institutions as it has become more available; however, there is a lack of data in this regard among healthy donors for allogeneic HSCT mobilization. In this study, we aim to compare the efficacy of Nivestym compared to Neupogen for allogeneic donor PBSC mobilization."

Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Oncology • Transplantation

Validation of Nivestym compared to Neupogen: An NMDP analysis. (PubMed, J Clin Apher) - No abstract available

Journal

Safe Administration of GCSF after Graded Challenge in Patient with Delayed Cutaneous Drug Hypersensitivity Reaction (ACAAI 2023) - "Subsequently, she began receiving low-dose SC filgrastim-aafi, due to insurance coverage restrictions...Despite receiving 2 doses of diphenhydramine, the rash persisted for 24 hours...She tolerated 0.5 mcg/kg of SC filgrastim (after pretreatment with cetirizine) in the office the next day...Discussion Delayed cutaneous drug hypersensitivity reactions frequently have a non-IgE-mediated mechanism. In cases with mild symptoms, a graded challenge may be implemented to safely administer the drug."

Clinical • Allergy • Dermatology • Hematological Disorders • Immunology • Neutropenia

Filgrastim Aafi (Nivestym) Use Increases the Total Cost of Collection in Allogeneic Peripheral Blood Stem Cell Donors (CAP 2023) - "We found that cost savings by switching to filgrastim aafi is highly dependent on the use of plerixafor and collection days required. Future studies will determine which subgroups may benefit from prophylactic use of plerixafor. Preimplementation and Postimplementation of Filgrastim Aafi"

Comparing the effectiveness of biosimilar filgrastim (Nivestim®) versus original filgrastim (Neupogen®) for stem cell mobilization in adult and pediatric healthy donors. (PubMed, J Oncol Pharm Pract) - "Biosimilar Nivestim® was as effective as the original, Neupogen®, for stem cell mobilization for healthy adult and pediatric donors. Larger randomized studies are necessary to evaluate the safety and transplant outcomes of the use of Nivestim®."

Journal • Review • Oncology • Pediatrics • Transplantation • CD34

EFFICACY AND SAFETY OF THE G-CSF BIOSIMILAR FILGRASTIM-AAFI COMPARED TO FILGRASTIM: A REPORT FROM THE NATIONAL MARROW DONOR PROGRAM (EBMT 2023) - "Mobilization and apheresis of an adequate cell dose with a normal graft composition while maintaining donor safety remains critical for the success of transplant programs across the world. These data provide reassurance that mobilization of volunteer unrelated donors with Nivestym results in comparable safety and efficacy compared to Neupogen."

Clinical • CNS Disorders • Fatigue • Hematological Disorders • Musculoskeletal Pain • Pain • Transplantation • CD34

Chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim in solid tumours versus haematological malignancies: Patterns, outcomes and determinants (MONITOR-GCSF study) (ESMO Asia 2017) - "Our analyses illustrate the importance of assuring adequate GCSF support in both haematology and solid tumour pts to prevent CIN/FN and related hospitalisations and chemotherapy disturbances."

Real-world evidence • Leukemia

Novel Lineage Depletion and Manufacturing Allows for Unprecedented Preservation of Autologous Blood Stem Cells for Gene Therapy of Fanconi Anemia Complementation Group Α (ASH 2017) - P1; "...Successful mobilization of CD34+ cells was achieved with combination filgrastim (16µg/kg BID or 32µg/kg/day) and plerixafor (240µg/kg)...Infusion was well-tolerated and a fourth patient is expected to be treated in the Fall of 2017. This novel method of depleting lineage positive cells reduced TNC counts to feasible numbers for transduction while maintaining high numbers of CD34+ cells, a strategy which could have benefits in other disease targets for gene therapy."

Biosimilar • Non-Hodgkin’s Lymphoma

Modifications to the “Classical” Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis: Efficacy and Safety Study of a Less Toxic Approach Which Improves the Neurological Condition. a Mexican Perspective (ASH 2017) - P=N/A; "Background: In an effort to reset the immune system, patients with multiple sclerosis (MS) have been autografted with stem cells; we have shown that these grafts can be performed on an outpatient basis with non-frozen peripheral blood hematopoietic stem cells (PBSC) and a conditioning regimen of cyclophosphamide (Cy) and rituximab, the so-called “Mexican method”... The Mexican autograft method in MS carries a very low morbidity and no mortality, induces neurological responses in MS, even in variants in which other autograft protocols have not proven useful, such as SP-MS and PP-MS. Additional information and follow-up is needed to further support these observations."

Clinical • Biosimilar • Hematological Malignancies • Multiple Sclerosis

Cost-efficiency analysis of conversion to biosimilar filgrastim for supportive cancer care and resultant expanded access analysis to supportive care and early-stage HER2+ breast cancer treatment in Saudi Arabia: Simulation study. (PubMed, J Med Econ) - "This study estimated, for Saudi Arabia, the cost-efficiency of converting patients from reference Neupogen1 and Neulastim to one of two filgrastim biosimilars (Nivestim, Zarzio); the budget-neutral expanded access to supportive care with biosimilar filgrastim and therapeutic care to ado-trastuzumab emtansine thus afforded; and the number-needed-to-convert (NNC) to provide supportive or therapeutic treatment to one patient. This simulation study demonstrated significant potential cost-savings from biosimilar conversion. These savings provide budget-neutral increased access to supportive and therapeutic cancer care."

Journal • Breast Cancer • Febrile Neutropenia • Hematological Disorders • HER2 Breast Cancer • Neutropenia • Oncology • Solid Tumor • CSF3 • HER-2

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

Effectiveness and Safety of Filgrastim (Neupogen™) versus Filgrastim-aafi (Nivestim™) in Primary Prophylaxis of Chemotherapy-Induced Febrile Neutropenia: An Observational Cohort Study. (PubMed, Drugs Real World Outcomes) - "Filgrastim and filgrastim-aafi had comparable effectiveness and safety as primary prophylaxis for chemotherapy-induced febrile neutropenia. More extensive prospective studies with additional insight on the cost implications are required."

Journal • Observational data • Chemotherapy-Induced Neutropenia • Febrile Neutropenia • Hematological Disorders • Neutropenia • Oncology

FDA-Approved Drugs (FDA) - Approval of Hospira's Nivestym on 05/03/2021.

sBLA • Neutropenia

Federal Court of Appeal dismisses appeal of first trial decision under the amended PMNOC Regulations (JD Supra) - "On November 3, 2020, the Federal Court of Appeal heard and dismissed the appeal of the first trial decision under the amended Patented Medicines (Notice of Compliance) Regulations: Amgen v Pfizer, 2020 FCA 188. Amgen had appealed the trial decision, previously reported here, which held obvious the asserted claims of Canadian Patent No. 1,341,537, relating to filgrastim (Amgen’s NEUPOGEN and Pfizer’s biosimilar product NIVESTYM)."

Corporate lawsuit • Neutropenia

Efficacy and Safety of Nivestim Versus Neupogen for Mobilization of Peripheral Blood Stem Cells for Autologous Stem Cell Transplantation. (PubMed, Sci Rep) - "No difference was observed for neutrophil and platelet engraftment after autoSCT. Nivestim was found to be safe and non-inferior to Neupogen for chemo-mobilization of stem cells for autoSCT, and associated with lower cost and shorter length of hospitalization."

Clinical • Journal • Transplantation

Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data. (PubMed, Toxicol Appl Pharmacol) - "Filgrastim, a biopharmaceutical listed on WHO model list of essential medicines, was approved in USA in 1991 for patients with non-myeloid malignancies associated with severe neutropenia and fever...Overall, 11,183 adverse drugs reaction reports were identified during observation period; of which 5764; 51.5% reports concerned to Neupogen®, the originator, and rest consists of Leucostim® (N = 680), Zarzio® (N = 622), Grasin® (N = 545), Nivestim® (N = 359) and Tevagrastim® (N = 152) biosimilars...Authors observed significant differences among originator and biosimilars in particular to efficacy, adverse events reported and time to onset of occurrences. Large epidemiologic studies are needed to further confirm these finding and provide additional insights."

Journal • Back Pain • Hematological Disorders • Musculoskeletal Pain • Neutropenia • Oncology • Pain

Oncology Care Model Spurs Use of Biosimilar Filgrastim (MJH Life Sciences) - "...OCM was associated with a greater than 20 percentage point impact on the use of biosimilar filgrastim for the three cancers they studied: breast (a 20.9% differece), lung (22.5%), and colorectal (27.5%)."

Clinical • Neutropenia

Long Term Follow up of Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Children and Teenagers < 18 Years Old with High-Risk Acute Leukemia. Very Good Results in CR1 and CR2 Patients but Unexpected High Incidence of Severe Acute Graft Versus Host Disease in Children < 10 Years (ASH 2017) - "...Two conditioning were used: fludarabine 30 mg/m2/day for 5 days, oral busulfan 4-8 mg/kg/split in 1-2 days and total body irradiation 400 cGy on day – 1 (Flu Bu TBI) or fludarabine, same dose, melphalan 100-140 mg/m2, one day and TBI 200-400 cGy on day - 1 (Flu Mel TBI). The patients received PTCy 50 mg/kg/day on D+3 and D+4, followed by cyclosporine and oral mycophenolate starting on day + 5...This study included only patients younger than 18 years with high risk leukemia transplanted with haplo PBSC and with PTCy. After a follow up of 26 months for surviving patients, the OS is outstanding for patients in CR1, encouraging for CR2 and satisfactory for advance disease, the TRM is not high and the overall incidence of acute and chronic GVHD acceptable, this confirm the value of this procedure in the population studied. However late relapsed occurred and we noticed, similar to an Indian report, (Biol Blood Marrow Transplant 2016; 22:499) a high incidence of severe aGVHD in...&qu

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Biosimilar • Chronic Myeloid Leukemia • Graft versus Host Disease