Pegfilgrastim
Pegfilgrastim is a pegylated, long-acting formulation of filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), that functions as a leukocyte growth factor to stimulate neutrophil production and reduce the incidence of febrile neutropenia in patients undergoing myelosuppressive chemotherapy for non-myeloid malignancies.[1] It is administered subcutaneously as a single 6 mg dose per chemotherapy cycle, typically at least 24 hours after chemotherapy administration, offering a convenient alternative to daily dosing required for non-pegylated G-CSF.[2] The mechanism of action involves pegfilgrastim binding to specific G-CSF receptors on the surface of hematopoietic progenitor cells and mature neutrophils, which promotes their proliferation, differentiation, survival, and functional activation, thereby accelerating neutrophil recovery from chemotherapy-induced myelosuppression.[1] The polyethylene glycol (PEG) conjugation extends its half-life to 15-80 hours compared to filgrastim's shorter duration, enabling self-regulation of serum levels through neutrophil-mediated clearance and reducing the need for multiple injections.[2] This pharmacokinetic profile results in peak serum concentrations 1-2 days after subcutaneous injection, with nonlinear elimination that decreases as the dose increases.[1] Pegfilgrastim was first approved by the U.S. Food and Drug Administration (FDA) on January 31, 2002, under the brand name Neulasta by Amgen Inc., for decreasing the incidence of infection manifested by febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of such events.[3] In 2015, its indications were expanded to increase survival in patients acutely exposed to myelosuppressive doses of radiation in the setting of acute radiation syndrome, with a recommended regimen of two 6 mg doses administered one week apart.[4] Pediatric dosing is weight-based for patients under 45 kg, such as 1.5 mg for those weighing 10-20 kg, to ensure appropriate neutrophil stimulation while minimizing risks like bone pain, the most common adverse effect.[2] Contraindications include hypersensitivity to pegfilgrastim or its components, with warnings for potential serious events such as splenic rupture, acute respiratory distress syndrome, and sickle cell crises in predisposed individuals.[1]Medical uses
Indications
Pegfilgrastim is primarily indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer chemotherapy associated with a clinically significant incidence of febrile neutropenia.[1] This approval is based on phase III clinical trials, including a placebo-controlled study in patients receiving docetaxel chemotherapy, demonstrating that a single 6 mg dose administered approximately 24 hours after chemotherapy significantly reduces the incidence of febrile neutropenia (from 17% with placebo to 1% with pegfilgrastim). Trials comparing pegfilgrastim to filgrastim showed equivalent reduction in the duration of severe neutropenia (approximately 1.7 days in cycle 1).[1] An additional approved indication is to increase survival in patients acutely exposed to myelosuppressive doses of radiation, as part of the hematopoietic subsyndrome of acute radiation syndrome, supported by efficacy data from animal models and limited human exposure scenarios.[1] Patient selection for prophylactic use in chemotherapy focuses on individuals with non-myeloid cancers, such as breast, lung, or ovarian cancer, undergoing regimens with a high risk of febrile neutropenia (greater than 20%), particularly those with risk factors including age 65 years or older, advanced disease stage, or poor performance status.[2][5] In supportive care settings, pegfilgrastim is used off-label following hematopoietic stem cell transplantation (HSCT) to accelerate neutrophil recovery, with phase II and III trials showing it shortens the duration of severe neutropenia by 1 to 2 days compared to daily filgrastim, achieving median recovery times of 8 to 10 days.[6][7] Similarly, it is employed in acute myeloid leukemia (AML) patients after induction chemotherapy to reduce neutropenia duration, though not approved for myeloid malignancies; clinical studies, including randomized phase II trials, report 50% to 70% reductions in neutropenia duration relative to controls in select cohorts.[8][9] Emerging off-label applications include management of severe chronic neutropenia, where small studies and case series indicate effective neutrophil elevation with less frequent dosing than filgrastim, though monitoring for dosing optimization is required.[10]Administration and dosage
Pegfilgrastim is administered as a fixed dose of 6 mg via subcutaneous injection once per chemotherapy cycle in adult patients receiving myelosuppressive chemotherapy.[1] This single-dose regimen differs from daily administration of the parent compound filgrastim, reflecting pegfilgrastim's prolonged half-life due to PEGylation.[1] The injection should occur no earlier than 24 hours after completion of chemotherapy and not within the 14-day period before the start of the next cycle to avoid interference with cytotoxic effects on bone marrow.[1] Common sites for subcutaneous injection include the abdomen, upper arm, or thigh, with rotation recommended to minimize local reactions.[1] Alternative formulations include the on-body injector (Neulasta Onpro), a single-use device applied to the skin on the day of chemotherapy, which automatically delivers the 6 mg dose approximately 27 hours later over about 45 minutes.[1] Biosimilars such as Ziextenzo (pegfilgrastim-bmez), Udenyca (pegfilgrastim-cbqv), and others follow equivalent dosing of 6 mg subcutaneously once per cycle, with no differences in administration protocols from the reference product Neulasta.[11][12] No dose adjustments are required based on body weight in adults, or for renal or hepatic impairment, as pharmacokinetic studies indicate no clinically significant alterations in these populations.[1][13] In pediatric patients weighing less than 45 kg, weight-based dosing is used (e.g., 1.5 mg for 10-20 kg body weight), but fixed 6 mg dosing applies for those 45 kg or greater.[1] For patients acutely exposed to myelosuppressive doses of radiation in the setting of acute radiation syndrome, the recommended regimen is two 6 mg subcutaneous doses administered one week apart for adults and pediatric patients weighing 45 kg or more. For pediatric patients weighing less than 45 kg, weight-based dosing is used (e.g., 1.5 mg for 10-20 kg body weight). The first dose should be administered as soon as possible after exposure.[14] Monitoring of absolute neutrophil count (ANC) is recommended prior to each chemotherapy cycle and periodically thereafter to assess response and guide timing, with a target ANC greater than 1,000/mm³ indicating recovery from neutropenia.[1] Complete blood counts, including ANC, should be evaluated to detect excessive leukocytosis (WBC >100 × 10⁹/L), which may warrant dose interruption.[1]Safety profile
Adverse effects
Pegfilgrastim is associated with several common adverse effects, primarily derived from clinical trials and post-marketing surveillance. The most frequently reported is bone pain, occurring in 31% of patients receiving pegfilgrastim compared to 26% in the placebo group in a pivotal placebo-controlled trial involving breast cancer patients undergoing myelosuppressive chemotherapy.[1] Pain in the extremities was also common, affecting 9% of pegfilgrastim-treated patients versus 4% in placebo recipients.[1] Injection site reactions, including pain, erythema, and swelling, are frequently observed, though specific incidence rates from trials are not quantified and are more commonly noted in post-approval use.[1] Fatigue and nausea have been reported as adverse effects, but they do not consistently show a greater than 5% difference compared to placebo in clinical studies.[1] Serious adverse effects are less common but can be severe. Splenomegaly has been identified in post-marketing reports, with an incidence of less than 1%, and requires monitoring via ultrasound if symptoms arise; splenic rupture, a potentially fatal complication, has also been reported rarely.[1] Acute respiratory distress syndrome (ARDS) is a rare but serious event, occurring in isolated cases during post-approval surveillance, and pegfilgrastim should be discontinued upon diagnosis.[1] In patients with sickle cell disorders, pegfilgrastim can precipitate severe or fatal sickle cell crises, warranting discontinuation if this occurs.[1] Capillary leak syndrome, which can lead to hypotension and organ dysfunction, has been reported infrequently in post-marketing experience and necessitates close monitoring with symptomatic supportive care.[1] Severe allergic reactions, including anaphylaxis, have been reported rarely in post-marketing data, and require immediate discontinuation of the drug.[2] Alveolar hemorrhage has been reported in post-marketing experience.[14] Management of adverse effects focuses on symptomatic relief and prompt intervention for serious events. Bone pain is typically managed with analgesics such as non-opioid pain relievers, and non-pharmacologic measures like rest may be employed.[1] For injection site reactions, local care including cool compresses is recommended. In cases of serious adverse effects like ARDS, sickle cell crises, capillary leak syndrome, or severe allergic reactions, pegfilgrastim must be permanently discontinued, with supportive treatments initiated as needed.[1] Patients should be monitored for signs of splenic enlargement, particularly those reporting abdominal or shoulder pain.[1]Contraindications and precautions
Pegfilgrastim is contraindicated in patients with a history of serious allergic reactions to pegfilgrastim, filgrastim, or components such as polyethylene glycol (PEG), with reported reactions including anaphylaxis.[1][13] It is not indicated for use in patients with chronic myeloid leukemia (CML) or myelodysplastic syndromes (MDS), and caution is advised due to the potential for tumor growth stimulation by granulocyte colony-stimulating factors (G-CSFs), with monitoring for MDS/AML progression recommended.[1][13] Precautions are advised in patients with sickle cell disease or trait, as pegfilgrastim may precipitate sickle cell crises, necessitating discontinuation if a crisis occurs.[1][13] Caution is recommended in individuals with a history of acute respiratory distress syndrome (ARDS), with prompt evaluation and discontinuation if signs such as fever, lung infiltrates, or respiratory distress emerge.[1][13] Pegfilgrastim should be avoided in patients with active infections until the underlying cause is addressed, as it does not treat the infection itself.[1] Additionally, monitor for rare complications such as aortitis (with symptoms like fever and abdominal or back pain) or glomerulonephritis (via urinalysis), discontinuing therapy if confirmed.[1][13] Drug interactions with lithium may potentiate neutrophil release, leading to leukocytosis, thus requiring close monitoring of white blood cell (WBC) counts during concurrent use.[1] Similarly, corticosteroids can have additive myeloproliferative effects with pegfilgrastim, warranting caution and WBC monitoring.[15] No significant interactions with the cytochrome P450 system are expected, given pegfilgrastim's biologic nature.[1] Special monitoring includes assessing baseline spleen size, as splenic rupture is a risk, and regular complete blood counts (CBCs) to avoid excessive leukocytosis (discontinue if WBC exceeds 50 × 10⁹/L).[1][13] Platelet counts and urinalysis should also be monitored periodically.[13]Pharmacology
Mechanism of action
Pegfilgrastim is a pegylated form of filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), designed to stimulate the production and maturation of neutrophils. It binds specifically to G-CSF receptors on the surface of hematopoietic progenitor cells and mature neutrophils within the bone marrow.[16] This binding initiates intracellular signaling cascades that promote the proliferation, differentiation, and enhanced survival of neutrophils, thereby increasing their release from the bone marrow storage pool into the bloodstream.[2] Upon receptor binding, pegfilgrastim induces dimerization of the G-CSF receptor, activating key downstream pathways such as JAK-STAT, which translocates to the nucleus to upregulate genes involved in neutrophil development and function. Additional pathways, including PI3K/AKT and MAPK/ERK, contribute to anti-apoptotic effects and functional activation of neutrophils, ensuring a rapid and sustained response to chemotherapy-induced myelosuppression.[16] The polyethylene glycol (PEG) conjugation in pegfilgrastim extends its plasma half-life compared to unmodified filgrastim by reducing renal clearance, while preserving the core receptor binding affinity and biological activity of the parent molecule.[17] This modification does not alter the dissociation constant (Kd) for G-CSF receptor binding, equivalent to filgrastim.[18] Pegfilgrastim exhibits a self-regulating mechanism through neutrophil-mediated clearance: as circulating neutrophil counts rise in response to treatment, the drug is internalized and degraded by these cells via receptor binding, leading to increased elimination and preventing excessive accumulation.[2] This feedback loop aligns drug exposure with the degree of neutropenia, optimizing therapeutic efficacy.[19]Pharmacokinetics
Pegfilgrastim exhibits nonlinear pharmacokinetics following subcutaneous administration, primarily due to its self-regulating clearance mediated by neutrophils.[19] AbsorptionPegfilgrastim is slowly absorbed after subcutaneous injection, with a time to peak plasma concentration (Tmax) of 1 to 2 days, which is slower than filgrastim because of the polyethylene glycol (PEG) moiety that promotes lymphatic uptake. The absolute bioavailability is lower than that of filgrastim, estimated at 20% to 50%, while relative bioavailability compared to a 30 μg/kg dose is approximately 80% to 94% at higher doses.[16][20][2] Distribution
The volume of distribution is approximately 170 L, consistent with distribution primarily in the extracellular fluid compartment and limited tissue binding beyond the bone marrow. No significant differences in distribution are observed based on age, gender, or renal function.[2][16][1] Metabolism and elimination
Pegfilgrastim is not metabolized by hepatic enzymes; instead, it undergoes nonspecific degradation following internalization by neutrophils via receptor binding. Clearance is predominantly neutrophil-mediated, resulting in reduced renal excretion compared to filgrastim, and is self-regulating such that it decreases with rising absolute neutrophil counts (ANC). The elimination half-life is dose-dependent, ranging from 15 to 80 hours (median approximately 42 hours). Pharmacokinetics are nonlinear, with higher systemic exposure observed at lower neutrophil counts due to diminished clearance.[1][19][2][16] Key parameters
The area under the concentration-time curve (AUC) increases more than proportionally with dose, reflecting the nonlinear clearance. Apparent serum clearance is approximately 14 mL/hour/kg and is lower at reduced ANC levels (e.g., inversely correlated with neutrophil-mediated elimination). This pattern aligns with the drug's mechanism of action, where clearance feedback is tied to neutrophil recovery.[19][2][1]
Chemistry
Molecular structure
Pegfilgrastim is a pegylated form of filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), consisting of filgrastim covalently conjugated to a 20 kDa monomethoxypolyethylene glycol (mPEG) molecule at the N-terminal methionyl residue via reductive alkylation.[1][21] This modification involves the attachment of the PEG aldehyde derivative to the amino group of the N-terminal methionine under mildly acidic conditions (pH 5), ensuring site-specific conjugation without altering the receptor-binding interface.[21] The protein core of pegfilgrastim comprises 175 amino acids, identical to the sequence of endogenous human G-CSF except for the addition of an N-terminal methionine residue required for bacterial expression.[1][21] The unmodified filgrastim portion has a molecular weight of approximately 19 kDa, while the addition of the 20 kDa PEG results in a total average molecular weight of about 39 kDa for pegfilgrastim.[1] Pegfilgrastim is produced through recombinant DNA technology, with the filgrastim polypeptide expressed in Escherichia coli bacteria via a genetically engineered plasmid containing the human G-CSF gene.[1][21] Following purification of the filgrastim, PEGylation is performed as a post-production step on the isolated protein. Due to its bacterial origin, pegfilgrastim lacks glycosylation, resulting in a non-glycosylated structure that differs from the naturally occurring glycosylated human G-CSF.[1][21] The PEGylation of pegfilgrastim increases its hydrodynamic radius from approximately 4 nm to 6 nm, which reduces renal clearance by limiting glomerular filtration while preserving the biological activity of the G-CSF moiety.[21] Additionally, this modification shields the protein from immune recognition, thereby decreasing immunogenicity compared to unmodified filgrastim.[21][22]Physical and chemical properties
Pegfilgrastim is formulated as a clear, colorless, preservative-free solution for subcutaneous injection, with a concentration of 10 mg/mL (based on protein content) in a 10 mM acetate buffer at pH 4.0, containing 5% sorbitol and 0.004% polysorbate 20 as excipients.[1][13][23] This formulation ensures compatibility with pre-filled syringes (typically 6 mg/0.6 mL) and supports direct subcutaneous administration without dilution.[1] The PEG modification enhances its aqueous solubility, making it highly soluble in water and buffered solutions suitable for parenteral use.[24] The protein exhibits an isoelectric point (pI) of approximately 6.2 (range 6.14–6.22), resulting in a net negative charge at physiological pH and contributing to its acidic behavior in formulation.[25][26] Pegfilgrastim is stable when stored refrigerated at 2–8°C, with a shelf life of up to 3 years in its original packaging, protected from light; per the FDA label, it should not be left at room temperature for more than 48 hours, while the EMA product information allows up to 72 hours at ≤30°C, after which it must be discarded if frozen or left at ambient conditions longer than specified to prevent degradation.[1][13] It is particularly sensitive to mechanical agitation, which can induce foaming and protein aggregation, and to improper storage, leading to chemical degradation pathways such as deamidation of asparagine or glutamine residues and oxidation of methionine or tryptophan.[25][27][28] Analytical characterization of pegfilgrastim relies on techniques such as reversed-phase high-performance liquid chromatography (RP-HPLC) for purity and oxidation assessment, size-exclusion HPLC (SE-HPLC) for aggregation detection, cation-exchange HPLC (CEX-HPLC) for charge variants, and mass spectrometry for site-specific modifications including PEG attachment and degradation products.[25][29][30] Nuclear magnetic resonance (NMR) spectroscopy confirms the covalent PEG linkage to the N-terminal methionine residue.[31][32] These methods ensure quality control by verifying structural integrity and stability under various stress conditions.[33][34]History
Development
Pegfilgrastim was developed by Amgen in the late 1990s as a PEGylated form of filgrastim, the recombinant human granulocyte colony-stimulating factor (G-CSF) marketed as Neupogen and approved by the FDA in 1991, to extend its circulating half-life and eliminate the need for daily subcutaneous injections during chemotherapy cycles.[35] The motivation stemmed from filgrastim's established role in stimulating neutrophil production to mitigate chemotherapy-induced neutropenia, but its short half-life necessitated multiple doses per cycle, posing patient inconvenience and compliance challenges.[35] PEGylation, the covalent attachment of a polyethylene glycol (PEG) chain to the N-terminal methionine of filgrastim, was selected based on prior research into protein modification techniques to enhance pharmacokinetics without substantially altering biological activity.[36] Research on PEG-filgrastim originated shortly after filgrastim's approval, with Amgen initiating PEGylation studies in the early 1990s to build on the molecule's pluripotent hematopoietic effects.[35] A key milestone was the filing of U.S. Patent Application No. 08/459,298 on June 2, 1995, covering methods for preparing PEGylated G-CSF analogs, which laid the intellectual property foundation for the drug's commercialization. Preclinical development focused on confirming the modified molecule's safety and efficacy in non-human models, serving as a bridge to filgrastim's established profile.[37] In preclinical studies, pegfilgrastim exhibited prolonged neutrophil stimulation in animal models, including cynomolgus monkeys, where a single dose sustained absolute neutrophil counts (ANC) for up to 10-14 days compared to filgrastim's shorter duration, due to reduced renal clearance from the PEG moiety.[37] Toxicity assessments in rodents and monkeys revealed dose-dependent bone marrow hyperplasia as the primary effect, consistent with G-CSF pharmacology, with no unexpected organ toxicities or immunogenicity at therapeutic levels; the no-observed-adverse-effect level (NOAEL) was established at 0.25 mg/kg in monkeys.[37] These findings supported advancement to clinical testing, confirming pegfilgrastim's potential for once-per-cycle administration while maintaining filgrastim's stimulatory potency on granulopoiesis.[38] Clinical development progressed through Phase I and II trials from 1998 to 2000, evaluating safety, pharmacokinetics, and pharmacodynamics in healthy volunteers and cancer patients receiving myelosuppressive chemotherapy.[35] In a multicenter Phase I/II dose-escalation study involving women with breast cancer treated with doxorubicin and docetaxel, single doses of pegfilgrastim (30-300 µg/kg) produced dose-proportional increases in ANC, with a 100 µg/kg dose achieving median ANC nadirs and recovery times comparable to daily filgrastim (5 µg/kg), and a favorable safety profile limited to mild bone pain.[35] These trials established the fixed 6 mg dose for further evaluation, demonstrating single-dose efficacy in preventing severe neutropenia without increased adverse events.[35] Pivotal Phase III trials conducted in 2001 confirmed efficacy. One multicenter trial randomized 310 breast cancer patients receiving four cycles of doxorubicin plus docetaxel to a single 100 µg/kg pegfilgrastim injection or daily filgrastim (5 µg/kg) per cycle.[1] A second trial randomized 157 patients to a single fixed 6 mg pegfilgrastim dose or daily filgrastim.[39] Results from both showed equivalent efficacy, with mean duration of severe neutropenia of approximately 1.7 days in the pegfilgrastim arms versus 1.6 days for filgrastim, and low febrile neutropenia incidence (around 3-13%), confirming non-inferiority (p < 0.001 for equivalence).[1][39] Safety was similar, with bone pain reported in 26% of pegfilgrastim patients versus 28% on filgrastim, supporting the molecule's transition to regulatory submission.[39] These milestones culminated in pegfilgrastim's readiness for approval by early 2002.[35]Regulatory approvals
Pegfilgrastim, marketed as Neulasta by Amgen, received initial approval from the U.S. Food and Drug Administration (FDA) on January 31, 2002, for decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.[3] This approval was supported by data from two randomized, double-blind, active-controlled phase III clinical trials involving a total of 467 patients with breast cancer (157 in one trial and 310 in the other), which demonstrated that pegfilgrastim was noninferior to daily 5 μg/kg doses of filgrastim in reducing the duration of severe neutropenia following myelosuppressive chemotherapy.[1] Subsequent label expansions included an indication in 2015 for increasing survival in patients acutely exposed to myelosuppressive doses of radiation, based on efficacy data from animal studies and supportive clinical evidence.[1] In Europe, the European Medicines Agency (EMA) granted centralized marketing authorization for Neulasta on August 22, 2002, for reducing the duration of neutropenia and the incidence of febrile neutropenia following cytotoxic chemotherapy for solid tumors, lymphoma, and acute myeloid leukemia (excluding chronic myeloid leukemia and myelodysplastic syndromes).[40] The authorization was based on similar phase III trial data showing noninferiority to filgrastim.[13] Pediatric use was later incorporated into the label following completion of a pediatric investigation plan, with evidence supporting its application in children aged 2 months and older receiving chemotherapy.[13] Pegfilgrastim was approved in other regions shortly following initial U.S. and EU authorizations, including in Canada on March 12, 2004, by Health Canada for indications consistent with FDA and EMA approvals to reduce neutropenia duration in chemotherapy patients.[41] In Australia, approval was granted by the Therapeutic Goods Administration in 2003 for decreasing febrile neutropenia incidence in nonmyeloid malignancy patients undergoing myelosuppressive chemotherapy. Approvals in Japan occurred later, with Kyowa Kirin receiving authorization for G-Lasta (pegfilgrastim) on September 26, 2014, for similar chemotherapy-induced neutropenia reduction.[42] The FDA approved the first pegfilgrastim biosimilar, Fulphila (pegfilgrastim-jmdb) by Mylan, on June 4, 2018, based on analytical, nonclinical, and clinical studies demonstrating similarity to Neulasta, including a phase III trial in 218 breast cancer patients showing comparable duration of severe neutropenia.[43] Subsequent approvals included Udenyca (pegfilgrastim-cbqv) on November 2, 2018; Ziextenzo (pegfilgrastim-bmez) on November 4, 2019; Nyvepria (pegfilgrastim-apgf) on June 10, 2020; Fylnetra (pegfilgrastim-pbbk) on May 26, 2022; Stimufend (pegfilgrastim-fpgk) on September 1, 2022; and Pyzchiva (pegfilgrastim-apgx) on October 30, 2023, all referencing Neulasta for the same core indications.[43][44] As of 2025, seven pegfilgrastim biosimilars had received FDA approval, enhancing access and competition in supportive cancer care.[45] Label updates for Neulasta have incorporated postmarketing safety data, including warnings for potential splenic rupture associated with splenomegaly added following reports of cases in 2005, and aortitis added in 2010 based on rare inflammatory vascular events observed in clinical use.[1] Beginning in 2023, certain pegfilgrastim biosimilars received FDA designations for interchangeability with Neulasta, allowing pharmacy-level substitution without prescriber intervention in applicable states.[46]Society and culture
Brand names and biosimilars
Pegfilgrastim is commercially available under the brand name Neulasta, developed and marketed by Amgen, which was approved by the FDA in January 2002 for reducing the incidence of infection in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy.[3] An on-body injector variant, Neulasta Onpro, was approved by the FDA in 2014 to provide automated subcutaneous delivery approximately 27 hours after activation.[47] Several biosimilars to Neulasta have been approved by the FDA, demonstrating no clinically meaningful differences from the reference product in terms of safety, purity, and potency. These include:- Fulphila (pegfilgrastim-jmdb) by Mylan and Biocon, approved in June 2018[48]
- Udenyca (pegfilgrastim-cbqv) by Coherus BioSciences, approved in November 2018[49]
- Ziextenzo (pegfilgrastim-bmez) by Sandoz, approved in November 2019[50]
- Nyvepria (pegfilgrastim-apgf) by Pfizer, approved in June 2020
- Fylnetra (pegfilgrastim-pbbk) by Amneal Pharmaceuticals, approved in May 2022[51]
- Stimufend (pegfilgrastim-fpgk) by Fresenius Kabi, approved in September 2022[52]