General Information

Neupogen (filgrastim) is a leukocyte growth factor. 

Neupogen is specifically indicated 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
• 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
• Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome)

Neupogen is supplied as an injection, for subcutaneous or intravenous use. The recommended dosing is as follows:

Patients with cancer receiving myelosuppressive chemotherapy or induction and/or consolidation chemotherapy for AML

• Recommended starting dose is 5 mcg/kg/day subcutaneous injection, short intravenous infusion (15 to 30 minutes), or continuous intravenous infusion. See Full Prescribing Information for recommended dosage adjustments and timing of administration

Patients with cancer undergoing bone marrow transplantation

• 10 mcg/kg/day given as an intravenous infusion no longer than 24 hours. See Full Prescribing Information for recommended dosage adjustments and timing of administration

Patients undergoing autologous peripheral blood progenitor cell collection and therapy

• 10 mcg/kg/day subcutaneous injection
• Administer for at least 4 days before first leukapheresis procedure and continue until last leukapheresis

Patients with congenital neutropenia

• Recommended starting dose is 6 mcg/kg subcutaneous injection twice daily

Patients with cyclic or idiopathic neutropenia

• Recommended starting dose is 5 mcg/kg subcutaneous injection daily

Patients acutely exposed to myelosuppressive doses of radiation

• 10 mcg/kg/day subcutaneous injection

Mechanism of Action

Neupogen (filgrastim) is a leukocyte growth factor. Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation. Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens). G-CSF is not species-specific and has been shown to have minimal direct in vivo or in vitro effects on the production or activity of hematopoietic cell types other than the neutrophil lineage.

Side Effects

Adverse effects associated with the use of Neupogen may include, but are not limited to, the following:

With non-myeloid malignancies receiving myelosuppressive anti-cancer drugs: pyrexia, pain, rash, cough, and dyspnea. (

With AML: pain, epistaxis and rash.

With non-myeloid malignancies undergoing myeloablative chemotherapy followed by BMT: rash.

Undergoing peripheral blood progenitor cell mobilization and collection: bone pain, pyrexia and headache.

With severe chronic neutropenia (SCN): pain, anemia, epistaxis, diarrhea, hypoesthesia and alopecia

Clinical Trial Results

Patients with Cancer Receiving Myelosuppressive Chemotherapy

The safety and efficacy of NEUPOGEN to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs were established in a randomized‚ double-blind‚ placebo-controlled trial conducted in patients with small cell lung cancer (Study 1). In Study 1, patients received up to 6 cycles of intravenous chemotherapy including intravenous cyclophosphamide and doxorubicin on day 1; and etoposide on days 1, 2, and 3 of 21 day cycles. Patients were randomized to receive NEUPOGEN (n = 99) at a dose of 230 mcg/m2 (4 to 8 mcg/kg/day) or placebo (n = 111). Study drug was administered subcutaneously daily beginning on day 4, for a maximum of 14 days. A total of 210 patients were evaluable for efficacy and 207 were evaluable for safety. 

The main efficacy endpoint was the incidence of febrile neutropenia. Febrile neutropenia was defined as an ANC < 1,000/mm3 and temperature > 38.2°C. Treatment with NEUPOGEN resulted in a clinically and statistically significant reduction in the incidence of infection‚ as manifested by febrile neutropenia, 40% for NEUPOGEN-treated patients and 76% for placebo-treated patients (p < 0.001). There were also statistically significant reductions in the incidence and overall duration of infection manifested by febrile neutropenia; the incidence, severity and duration of severe neutropenia (ANC < 500/mm3 ); the incidence and overall duration of hospital admissions; and the number of reported days of antibiotic use.

Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy

The safety and efficacy of NEUPOGEN 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) was established in a randomized, double-blind‚ placebo-controlled‚ multi-center trial in patients with newly diagnosed, de novo AML (Study 4). In Study 4 the initial induction therapy consisted of intravenous daunorubicin days 1, 2, and 3; cytosine arabinoside days 1 to 7; and etoposide days 1 to 5. Patients were randomized to receive subcutaneous NEUPOGEN (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 (ANC ≥ 1,000/mm3 for 3 consecutive days or ≥ 10,000/mm3 for 1 day) or for a maximum of 35 days. 

The main efficacy endpoint was median duration of severe neutropenia defined as neutrophil count < 500/mm3 . Treatment with NEUPOGEN resulted in a clinically and statistically significant reduction in median number of days of severe neutropenia, NEUPOGEN-treated patients 14 days, placebo-treated patients 19 days (p = 0.0001: difference of 5 days (95% CI: -6.0, -4.0)). There was a reduction in the median duration of intravenous antibiotic use, NEUPOGEN-treated patients: 15 days versus placebo-treated patients: 18.5 days; a reduction in the median duration of hospitalization, NEUPOGEN-treated patients: 20 days versus placebo-treated patients: 25 days. There were no statistically significant differences between the NEUPOGEN and the placebo groups in complete remission rate (69% - NEUPOGEN, 68% - placebo), median time to progression of all randomized patients (165 days - NEUPOGEN, 186 days - placebo), or median overall survival (380 days - NEUPOGEN, 425 days - placebo).

Patients with Cancer Undergoing Bone Marrow Transplantation

The safety and efficacy of NEUPOGEN to reduce the duration of neutropenia in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by autologous bone marrow transplantation was evaluated in 2 randomized controlled trials of patients with lymphoma (Study 6 and Study 9). The safety and efficacy of NEUPOGEN to reduce the duration of neutropenia in patients undergoing myeloablative chemotherapy followed by allogeneic bone marrow transplantation was evaluated in a randomized placebo-controlled trial (Study 10). In Study 6, patients with Hodgkin’s disease received a preparative regimen of intravenous cyclophosphamide, etoposide, and BCNU (“CVP”), and patients with non-Hodgkin’s lymphoma received intravenous BCNU, etoposide, cytosine arabinoside and melphalan (“BEAM”). There were 54 patients randomized 1:1:1 to control, NEUPOGEN 10 mcg/kg/day, and NEUPOGEN 30 mcg/kg/day as a 24-hour continuous infusion starting 24 hours after bone marrow infusion for a maximum of 28 days. 

The main efficacy endpoint was duration of severe neutropenia ANC < 500/mm3 . A statistically significant reduction in the median number of days of severe neutropenia (ANC < 500/mm3 ) occurred in the NEUPOGEN-treated groups versus the control group (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]). In Study 9, patients with Hodgkin’s disease and non-Hodgkin’s lymphoma received a preparative regimen of intravenous cyclophosphamide, etoposide, and BCNU (“CVP”). There were 43 evaluable patients randomized to continuous subcutaneous infusion NEUPOGEN 10 mcg/kg/day (n = 19), NEUPOGEN 30 mcg/kg/day (n = 10) and no treatment (n = 14) starting the day after marrow infusion for a maximum of 28 days. The median age was 33 (range 17 to 56) years; 67% males; 28% Hodgkin’s disease and 72% non-Hodgkin’s lymphoma. The main efficacy endpoint was duration of severe neutropenia. There was statistically significant reduction in the median number of days of severe neutropenia (ANC < 500/mm3 ) in the NEUPOGEN-treated groups versus the control group (21.5 days in the control group versus 10 days in the NEUPOGEN-treated groups, p < 0.001). The number of days of febrile neutropenia was also reduced significantly in this study (13.5 days in the control group versus 5 days in the NEUPOGEN-treated groups‚ p < 0.0001). In Study 10, 70 patients scheduled to undergo bone marrow transplantation for multiple underlying conditions using multiple preparative regimens were randomized to receive NEUPOGEN 300 mcg/m2 /day (n = 33) or placebo (n = 37) days 5 through 28 after marrow infusion. The median age was 18 (range 1 to 45) years, 56% males. The underlying disease was: 67% hematologic malignancy, 24% aplastic anemia, 9% other. A statistically significant reduction in the median number of days of severe neutropenia occurred in the treated group versus the control group (19 days in the control group and 15 days in the treatment group‚ p < 0.001) and time to recovery of ANC to ≥ 500/mm3 (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

The safety and efficacy of NEUPOGEN to mobilize autologous peripheral blood progenitor cells for collection by leukapheresis was supported by the experience in uncontrolled trials, and a randomized trial comparing hematopoietic stem cell rescue using NEUPOGEN-mobilized autologous peripheral blood progenitor cells to autologous bone marrow (Study 11). Patients in all these trials underwent a similar mobilization/collection regimen: NEUPOGEN was administered for 6 to 7 days‚ in most cases the apheresis procedure occurred on days 5‚ 6, and 7. The dose of NEUPOGEN ranged between 10 to 24 mcg/kg/day and was administered subcutaneously by injection or continuous intravenous infusion. 

Engraftment was evaluated in 64 patients who underwent transplantation using NEUPOGEN-mobilized autologous hematopoietic progenitor cells in uncontrolled trials. Two of the 64 patients (3%) did not achieve the criteria for engraftment as defined by a platelet count ≥ 20‚000/mm3 by day 28. In clinical trials of NEUPOGEN for the mobilization of hematopoietic progenitor cells‚ NEUPOGEN was administered to patients at doses between 5 to 24 mcg/kg/day after reinfusion of the collected cells until a sustainable ANC (≥ 500/mm3 ) was reached. The rate of engraftment of these cells in the absence of NEUPOGEN post transplantation has not been studied.

Study 11 was a randomized, unblinded study of patients with Hodgkin’s disease or non-Hodgkin’s lymphoma undergoing myeloablative chemotherapy‚ 27 patients received NEUPOGEN-mobilized autologous hematopoietic progenitor cells and 31 patients received autologous bone marrow. The preparative regimen was intravenous BCNU, etoposide, cytosine arabinoside and melphalan (“BEAM”). Patients received daily NEUPOGEN 24 hours after stem cell infusion at a dose of 5 mcg/kg/day. The main efficacy endpoint was number of days of platelet transfusions. Patients randomized to NEUPOGEN-mobilized autologous peripheral blood progenitor cells compared to autologous bone marrow had significantly fewer days of platelet transfusions (median 6 vs 10 days).

Patients with Severe Chronic Neutropenia

The safety and efficacy of NEUPOGEN to reduce the incidence and duration of sequelae of neutropenia (that is fever‚ infections, oropharyngeal ulcers) in symptomatic adult and pediatric patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia was established in a randomized controlled trial conducted in patients with severe neutropenia (Study 7). Patients eligible for Study 7 had a history of severe chronic neutropenia documented with an ANC < 500/mm3 on three occasions during a 6-month period, or in patients with cyclic neutropenia 5 consecutive days of ANC < 500/mm3 per cycle. In addition, patients must have experienced a clinically significant infection during the previous 12 months. Patients were randomized to a 4-month observation period followed by NEUPOGEN treatment or immediate NEUPOGEN treatment. The median age was 12 years (range 7 months to 76 years); 46% males; 34% idiopathic, 17% cyclic and 49% congenital neutropenia. NEUPOGEN was administered subcutaneously. The dose of NEUPOGEN was determined by the category of neutropenia.

Initial dose of NEUPOGEN:  Idiopathic neutropenia: 3.6 mcg/kg/day  Cyclic neutropenia: 6 mcg/kg/day  Congenital neutropenia: 6 mcg/kg/day divided 2 times per day. The dose was increased incrementally to 12 mcg/kg/day divided 2 times per day if there was no response.

The main efficacy endpoint was response to NEUPOGEN treatment. ANC response from baseline (< 500/mm3 ) was defined as follows:  Complete response: median ANC > 1,500/mm3  Partial response: median ANC ≥ 500/mm3 and ≤ 1,500/mm3 with a minimum increase of 100%  No response: median ANC < 500/mm3 There were 112 of 123 patients who demonstrated a complete or partial response to NEUPOGEN treatment.

Patients Acutely Exposed to Myelosuppressive Doses of Radiation (Hematopoietic Syndrome of Acute Radiation Syndrome)

Efficacy studies of NEUPOGEN could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. Approval of this indication was based on efficacy studies conducted in animals and data supporting the use of NEUPOGEN for other approved indications.