Eflapegrastim

Identification

Summary

Eflapegrastim is a form of recombinant human granulocyte colony stimulating factor used to induce the production of granulocytes and lower infection risk after myelosuppressive therapy.

Brand Names
Rolvedon
Generic Name
Eflapegrastim
DrugBank Accession Number
DB15001
Background

Febrile neutropenia (FN), defined as the co-occurrence of fever (temperature > 38 ◦C) and severe neutropenia (ANC < 500 cells/mm3), is a potential side effect of myelosuppressive chemotherapy in which the patient develops an infection during a period of significant neutropenia.2 It typically develops during the first cycle of chemotherapy and is associated with an increased risk of morbidity and mortality. The primary factor associated with FN risk is the chemotherapy regimen being administered - regimens are classified as either high-, intermediate-, or low-risk for FN, and relevant guidelines recommend the use of pharmacologic prophylaxis against FN in patients receiving high-risk regimens and those receiving intermediate-risk regimens who have ≥1 additional risk factor.2

Granulocyte-colony stimulating factors (G-CSFs) - which include filgrastim and pegfilgrastim - were first used clinically in the 1990s and are the primary means of prophylaxis against chemotherapy-induced neutropenia, including FN.2 They trigger signaling pathways that control the differentiation, proliferation, migration, and survival of neutrophils, thereby helping to restore depressed neutrophil counts.3

Eflapegrastim is a form of recombinant human G-CSF comprising a human G-CSF analog coupled to the Fc fragment of human IgG4 via a polyethylene glycol linker.3 In September 2022, eflapegrastim was approved by the US FDA as a prophylactic against infection, as manifested by febrile neutropenia, in patients receiving certain myelosuppressive anti-cancer drugs.5

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Haematopoietic growth factors
Protein Chemical Formula
Not Available
Protein Average Weight
72000.0 Da
Sequences
>SUBUNIT_1
PSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHN
AKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP
QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_2
PSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHN
AKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP
QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_3
TPLGPASSLPQSFLLKSLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAP
LSSCSSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQ
MEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
References:
  1. NIH Inxight: Eflapegrastim [Link]
Download FASTA Format
Synonyms
  • Eflapegrastim
External IDs
  • HM-10460A
  • HM10460A
  • HNK-460
  • HNK460
  • SPL-2012

Pharmacology

Indication

Eflapegrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.3

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Prevention ofInfection•••••••••••••••••••••••••••• •••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Eflapegrastim increases absolute neutrophil count (ANC) in a dose-dependent manner in both healthy subjects and cancer patients.3 In rat studies, it was associated with higher serum and bone marrow concentrations than pegfilgrastim, which translated to a significantly shorter duration of neutropenia when eflapegrastim was administered 24 hours post-chemotherapy compared to pegfilgrastim.2

Mechanism of action

Eflapegrastim is a recombinant human granulocyte-colony stimulating factor (rhG-CSF). Like endogenous G-CSF, eflapegrastim binds to G-CSF receptors on myeloid progenitor cells and neutrophils - this triggers signaling pathways that result in neutrophil differentiation, proliferation, migration, and survival.3

TargetActionsOrganism
AGranulocyte colony-stimulating factor receptor
ligand
Humans
Absorption

The Tmax of eflapegrastim is dose-dependent and increases with increasing dose.1 Following administration of the recommended dosage in patients with breast cancer, the median Tmax of eflapegrastim-xnst is 25 hours.3

Volume of distribution

The volume of distribution of eflapegrastim-xnst is 1.44 L.3

Protein binding

Not Available

Metabolism

Eflapegrastim is likely metabolized via endogenous degradation following internalization by cells expressing G-CSF receptors.3

Route of elimination

Following subcutaneous administration, eflapegrastim is not detectable in the urine.3,1

Half-life

In patients with breast cancer, the geometric mean half-life of eflapegrastim-xnst is 36.4 hours.3

Clearance

The clearance of eflapegrastim-xnst decreased with increasing dose, suggesting target-mediated clearance by neutrophils.3 With repeat dosing clearance appears to increase, potentially due to the subsequent increase in circulating neutrophils.3

Adverse Effects
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Toxicity

An overdose of eflapegrastim may result in leukocytosis and bone pain.3 In the event of an overdose, the patient should be monitored for adverse effects and general supportive measures should be implemented as necessary.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Eflapegrastim.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Eflapegrastim.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Eflapegrastim.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Eflapegrastim.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Eflapegrastim.
Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RolvedonInjection, solution13.2 mg/0.6mLSubcutaneousSpectrum Pharmaceuticals, Inc.2022-10-18Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans

Chemical Identifiers

UNII
UT99UG9QJX
CAS number
1384099-30-2

References

General References
  1. Shin KH, Kim TE, Lim KS, Yoon SH, Cho JY, Kim SE, Park KM, Shin SG, Jang IJ, Yu KS: Pharmacokinetic and pharmacodynamic properties of a new long-acting granulocyte colony-stimulating factor (HM10460A) in healthy volunteers. BioDrugs. 2013 Apr;27(2):149-58. doi: 10.1007/s40259-013-0010-0. [Article]
  2. Blayney DW, Schwartzberg L: Chemotherapy-induced neutropenia and emerging agents for prevention and treatment: A review. Cancer Treat Rev. 2022 Sep;109:102427. doi: 10.1016/j.ctrv.2022.102427. Epub 2022 Jun 21. [Article]
  3. FDA Approved Drug Products: Rolvedon (eflapegrastim-xnst) for subcutaneous injection [Link]
  4. NIH Inxight: Eflapegrastim [Link]
  5. Cancer Network: FDA Approves Eflapegrastim Injection to Decrease Febrile Neutropenia–Related Infection in Non–Myeloid Malignancies [Link]
RxNav
2612526
Wikipedia
Eflapegrastim

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentBreast Neoplasms1
3CompletedTreatmentBreast Cancer / Neutropenia2
2CompletedTreatmentNeutropenia1
2RecruitingTreatmentLymphoma / Solid Tumors1
1CompletedTreatmentBreast Cancer / Pharmacokinetics1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous13.2 mg/0.6mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
General Function
Receptor activity
Specific Function
Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutroph...
Gene Name
CSF3R
Uniprot ID
Q99062
Uniprot Name
Granulocyte colony-stimulating factor receptor
Molecular Weight
92155.615 Da
References
  1. FDA Approved Drug Products: Rolvedon (eflapegrastim-xnst) for subcutaneous injection [Link]

Drug created at May 20, 2019 14:41 / Updated at December 01, 2022 11:29