Nivestym – Pfizer – Second biosimilar to Filgrastim (Neupogen ®) in the U.S.

Generic Name Brand Name Manufacturer Approval Date Anticipated Availability Accelerated Review
filgrastim-aafi Nivestym ™ Pfizer Inc. 07/20/2018 n/a n/a
Labeled Indications
Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever
Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML)
Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with non-myeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT)
Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
Reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia
Drug Class Comparative Drugs in Class
Granulocyte colony-stimulating factors (G-CSFs) (filgrastim) Neupogen/Zarxio,

(tbo-filgrastim) Granix

(pegfilgrastim) Neulasta/Fulphila

Mechanism of Action:
Nivestym ™ acts on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation
Clinical Trial Summary:
The package insert contains study results to support each of the approved indications.

 

Patients with Cancer Receiving Myelosuppressive Chemotherapy

Study 1 – randomized‚ double-blind‚ placebo-controlled trial conducted in patients with small cell lung cancer

Chemotherapy: intravenous cyclophosphamide and doxorubicin on day 1; and etoposide on days 1, 2, and 3 of 21 day cycle for 6 cycles

Intervention: filgrastim (n = 99) at a dose of 230 mcg/m2 (4 to 8 mcg/kg/day) or placebo (n = 111) beginning on day 4, for a maximum of 14 days

Primary Endpoint: incidence of febrile neutropenia, filgrastim resulted in a clinically and statistically significant reduction in the incidence of infection, 40% for filgrastim -treated patients and 76% for placebo-treated patients (p < 0.001)

 

Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy

Study 4 – randomized, double-blind‚ placebo-controlled‚ multi-center trial in patients with newly diagnosed, de novo AML

Chemotherapy: intravenous daunorubicin days 1, 2, and 3; cytosine arabinoside days 1 to 7; and etoposide days 1 to 5 as induction therapy

Intervention: filgrastim (n = 259) at a dose of 5 mcg/kg/day or placebo (n = 262) from 24 hours after the last dose of chemotherapy until neutrophil recovery or for a maximum of 35 days

Primary Endpoint: median duration of severe neutropenia, filgrastim-treated patients 14 days, placebo-treated patients 19 days (p = 0.0001: difference of 5 days (95% CI: -6.0, -4.0))

 

Patients with Cancer Undergoing Bone Marrow Transplantation

Study 6 and 9 – randomized controlled trials of patients with lymphoma undergoing myeloablative chemotherapy followed by autologous bone marrow transplantation

Study 10 – randomized placebo controlled trial of patients undergoing myeloablative chemotherapy followed by allogeneic bone marrow transplantation

Study 6

Chemotherapy: Hodgkin’s disease: intravenous cyclophosphamide, etoposide, and BCNU (“CVP”), Non-Hodgkin’s lymphoma intravenous BCNU, etoposide, cytosine arabinoside and melphalan (“BEAM”)

Intervention: 1:1:1 to control, filgrastim 10 mcg/kg/day, and filgrastim 30 mcg/kg/day as a 24 hour continuous infusion starting 24 hours after bone marrow infusion for a maximum of 28 days

Primary Endpoint: duration of severe neutropenia, 23 days in the control group‚ 11 days in the 10 mcg/kg/day group, and 14 days in the 30 mcg/kg/day group [11 days in the combined treatment groups‚ p = 0.004]

Study 9

Chemotherapy: intravenous cyclophosphamide, etoposide, and BCNU (“CVP”)

Intervention: continuous subcutaneous infusion filgrastim 10 mcg/kg/day (n = 19), filgrastim 30 mcg/kg/day (n = 10) and no treatment (n = 14) starting the day after marrow infusion for a maximum of 28 days

Primary Endpoint: duration of severe neutropenia, 21.5 days in the control group versus 10 days in the filgrastim-treated groups, p < 0.001

Study 10

Chemotherapy: multiple preparative regimens

Intervention: filgrastim 300 mcg/m2/day (n = 33) or placebo (n = 37) days 5 through 28 after marrow infusion

Primary Endpoint: reduction in the median number of days of severe neutropenia, 19 days in the control group and 15 days in the treatment group‚ p < 0.001 and time to recovery 21 days in the control group and 16 days in the treatment group‚ p < 0.001

 

Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy

Uncontrolled trials and a randomized, unblinded trial comparing hematopoietic stem cell rescue using filgrastim mobilized autologous peripheral blood progenitor cells to autologous bone marrow (Study 11)

Intervention: filgrastim between 10 to 24 mcg/kg/day was administered for 6 to 7 days administered subcutaneously or continuous intravenous infusion

Study 11 – lymphoma patients undergoing myeloablative chemotherapy

Chemotherapy: preparative regimen was intravenous BCNU, etoposide, cytosine arabinoside and melphalan (“BEAM”)

Intervention: 27 patients received filgrastim-mobilized autologous hematopoietic progenitor cells and 31 patients received autologous bone marrow.  Patients also received daily filgrastim 24 hours after stem cell infusion at a dose of 5 mcg/kg/day

Primary Endpoint: number of days of platelet transfusions, median 6 days for filgrastim-mobilized autologous peripheral blood progenitor cells vs 10 days for autologous bone marrow

 

Patients with Severe Chronic Neutropenia

Study 7 – randomized controlled trial conducted in patients with severe neutropenia

Intervention: Patients were randomized to a 4 month observation period followed by filgrastim treatment or immediate filgrastim treatment, with dose determined by the category of neutropenia

Primary Endpoint: response to filgrastim, 112 of 123 patients demonstrated a complete or partial response to filgrastim treatment

Warnings and Adverse Effects (AE):
Warning(s): fatal splenic rupture, acute respiratory distress syndrome (ARDS), serious allergic reactions, fatal sickle cell crisis and glomerulonephritis
AE (most common): pyrexia, pain, rash, cough, dyspnea, epistaxis, headache, anemia, diarrhea, hypoesthesia and alopecia
NDC Strength Volume Single Dose Vial (SDV) / (Multi Dose Vial (MDV) Storage
00069-0293-10 300 mcg/ml 1 ml SDV (pack of 10 vials) Refrigeration
00069-0294-10 480 mcg/ml 1.6 ml SDV (pack of 10 vials) Refrigeration
00069-0291-01 300 mcg/0.5ml 0.5 ml Single-dose prefilled syringe Refrigeration
00069-0291-10 300 mcg/0.5ml 0.5 ml Single-dose prefilled syringe (10 pack) Refrigeration
00069-0292-01 480 mcg/0.8ml 0.8ml Single-dose prefilled syringe Refrigeration
00069-0292-10 480 mcg/0.8ml 0.8ml Single-dose prefilled syringe (10 pack) Refrigeration
Drug Sales Forecast (in millions):
  2018(F) 2019(F) 2020(F) 2021(F) 2022(F) 2023(F)
Global 32 43 67 81 95 103

 

References:

Product Labeling https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761080s000lbl.pdf  (Accessed 07/24/18)

Pharmaceutical Company press release https://www.pfizer.com/news/press-release/press-release-detail/u_s_fda_approves_pfizer_s_biosimilar_nivestym_filgrastim_aafi   (Accessed 07/25/18)

RJ Health Systems Web Site https://www.reimbursementcodes.com (Accessed 07/25/2018)

Global Data, Pharma Intelligence Web Site, View Drug Overview Site https://pharma.globaldata.com (Accessed 07/25/2018)


For a review of the 2018 drug pipeline please click here.

The latest updates are provided in a RJ Health monthly newsletter. Please click here to be directed to the June newsletter

Leave a Reply