Efbemalenograstim alfa

Identification

Summary

Efbemalenograstim alfa is a granulocyte-colony stimulating factor used to treat prevent chemotherapy-induced neutropenia.

Brand Names
Ryzneuta
Generic Name
Efbemalenograstim alfa
DrugBank Accession Number
DB18704
Background

Efbemalenograstim alfa is a long-acting recombinant fusion protein of granulocyte-colony stimulating factor (G-CSF) due to the addition of the Fc portion of human IgG2, allowing for once-per-cycle administration.4,1 As endogenous G-CSF mediates the differentiation of hematopoietic stem cells into granulocytes and eventually neutrophils, the administration of recombinant G-CSF like efbemalenograstim alfa can stimulate the production of neutrophils and thus reducing the severity and duration of neutropenia.2,3

On November 22, 2023, efbemalenograstim alfa was approved by the FDA under the brand name Ryzneuta for the treatment of chemotherapy-induced neutropenia in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. This approval was contingent on positive results observed in two pivotal Phase 3 Studies GC-627-04 and GC-627-05 in the US and Europe respectively.5

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Fusion proteins
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
>SUBUNIT_1
TPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAP
LSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQ
MEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQPGSGGGS
GGGGSGGGGSVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQ
FNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPASIEK
TISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT
PPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>SUBUNIT_2
TPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWAP
LSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQQ
MEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQPGSGGGS
GGGGSGGGGSVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQ
FNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPASIEK
TISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT
PPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
References:
  1. NIH Inxight: Efbemalenograstim alfa [Link]
Download FASTA Format
Synonyms
  • Benegrastim
  • Recombinant dimeric g-csf fusion protein f627
  • Rh g-csf fc fusion protein f-627
External IDs
  • F-627
  • F627

Pharmacology

Indication

Efbemalenograstim alfa 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 clinically significant incidence of febrile neutropenia.4

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

Over the tested dose range of 30 to 360 μg/kg in healthy adult males, neutrophils generally increased in a dose-dependent manner; however, the effect on neutrophils plateaued at the top two doses of 240 and 360 μg/kg.4

In patients with breast cancer given EC chemotherapy, in cycle 1, median ANC peaked on Day 4 (about 24 hours after efbemalenograstim alfa-vuxw administration) for the 240 and 320 μg/kg doses, declined to nadir on Days 8–9, and then recovered to a count of 2.0 × 109/L and higher by Day 11. The ANC levels in cycles 2, 3, and 4 tended to be higher than those observed in cycle 1.4

In patients with breast cancer given TAC chemotherapy, in cycle 1, median ANC peaked on Day 3 (about 24 hours after efbemalenograstim alfa-vuxw administration) in cycle 1 and 3, reached nadir on Day 8, and recovered to 2.0 x 109/L on Days 9 and 10 for the 320 μg/kg and 240 μg/kg doses, respectively. Mean ANC nadir was higher with 320 μg/kg compared to 240 μg/kg in both cycle 1 (0.75 x 109/L and 0.29 x 109/L, respectively), and cycle 3 (1.19 x 109/L and 0.57 x 109/L, respectively).4

Mechanism of action

Efbemalenograstim alfa-vuxw is a colony-stimulating factor that acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end-cell functional activation.4

TargetActionsOrganism
AGranulocyte colony-stimulating factor receptor
stimulator
Humans
Absorption

The median tmax of efbemalenograstim alfa-vuxw administered as 80 to 320 μg/kg in female patients with breast cancer receiving EC chemotherapy ranged from 24 hours to 48 hours in Cycle 1 and 9 to 30 hours in Cycle 3. The median tmax of efbemalenograstim alfa-vuxw administered as 240 to 320 μg/kg in female participants with breast cancer receiving TAC chemotherapy was 36 hours in Cycle 1 and ranged from 24 to 30 hours in Cycle 3.4

Volume of distribution

The geometric mean (CV%) apparent volume of distribution of efbemalenograstim alfa-vuxw was 18.8 L (257%) in Cycle 1 and 40.7 L (387%) in Cycle 3 in female patients with breast cancer.4

Protein binding

There is limited information on the protein binding of efbemalenograstim alfa-vuxw

Metabolism

Efbemalenograstim alfa-vuxw is expected to be metabolized into small peptides by catabolic pathways.4

Route of elimination

Neutrophil receptor binding is an important component of the clearance of efbemalenograstim alfa-vuxw, and serum clearance is directly related to the number of neutrophils.4

Half-life

The geometric mean (CV%) elimination half-life of efbemalenograstim alfa-vuxw was 35.6 h (108%) in Cycle 1 and 36.9 h (120%) in Cycle 3.4

Clearance

The geometric mean (CV%) apparent clearance of efbemalenograstim alfa-vuxw was 0.36 L/h (110%) in Cycle 1 and 0.76 L/h (167%) in Cycle 3.4

Adverse Effects
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Toxicity

Although available data on efbemalenograstim alfa use in pregnant women are insufficient to establish whether there is a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, there are available data from published studies in pregnant women exposed to other human G-CSF products. These studies have not established an association of G-CSF product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes.4

In animal studies, no evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats and rabbits that received cumulative doses of efbemalenograstim alfa-vuxw approximately 2.6 and 0.7 times, respectively, the recommended human dose (based on body surface area).4

Overdosage of efbemalenograstim alfa may result in leukocytosis and bone pain. In the event of an overdose, general supportive measures should be instituted, as necessary. Monitor the patient for adverse reactions.4

No carcinogenicity or mutagenesis studies have been conducted with efbemalenograstim alfa-vuxw.4

Efbemalenograstim alfa did not affect reproductive performance or fertility in male or female rats at cumulative weekly doses approximately 2.2 times higher than the recommended human dose (based on body surface area).4

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
CyclophosphamideThe risk or severity of pulmonary toxicity can be increased when Efbemalenograstim alfa is combined with Cyclophosphamide.
TopotecanThe risk or severity of neutropenia can be increased when Efbemalenograstim alfa is combined with Topotecan.
VinblastineThe risk or severity of peripheral neuropathy can be increased when Efbemalenograstim alfa is combined with Vinblastine.
VincristineThe risk or severity of peripheral neuropathy can be increased when Efbemalenograstim alfa is combined with Vincristine.
VindesineThe risk or severity of peripheral neuropathy can be increased when Efbemalenograstim alfa is combined with Vindesine.
Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RyzneutaInjection, solution20 mgSubcutaneousEvive Biotechnology Ireland Ltd2024-07-10Not applicableEU flag
RyzneutaInjection20 mg/1mLSubcutaneousEvive Biotechnology Singapore PTE. LTD.2023-11-23Not applicableUS flag

Categories

ATC Codes
L03AA18 — Efbemalenograstim alfa
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
Not Available

Chemical Identifiers

UNII
5UPW5HJW3O
CAS number
2200269-79-8

References

General References
  1. Shayne M, Harvey RD, Lyman GH: Prophylaxis and treatment strategies for optimizing chemotherapy relative dose intensity. Expert Rev Anticancer Ther. 2021 Oct;21(10):1145-1159. doi: 10.1080/14737140.2021.1941891. Epub 2021 Jun 21. [Article]
  2. Mehta HM, Malandra M, Corey SJ: G-CSF and GM-CSF in Neutropenia. J Immunol. 2015 Aug 15;195(4):1341-9. doi: 10.4049/jimmunol.1500861. [Article]
  3. Cosler LE, Eldar-Lissai A, Culakova E, Kuderer NM, Dale D, Crawford J, Lyman GH: Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective. Pharmacoeconomics. 2007;25(4):343-51. doi: 10.2165/00019053-200725040-00006. [Article]
  4. FDA Approved Drug Products: RYZNEUTA® (efbemalenograstim alfa-vuxw) injection, for subcutaneous use I [Link]
  5. Evive Biotech and Acrotech Biopharma Announce FDA Approval of Ryzneuta® (Efbemalenograstim alfa Injection) for Chemotherapy-Induced Neutropenia (CIN) [Link]
RxNav
2670630
Wikipedia
Efbemalenograstim_alfa

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
3CompletedSupportive CareBreast Cancer1somestatusstop reasonjust information to hide
3CompletedTreatmentBreast Cancer / Neutropenia2somestatusstop reasonjust information to hide
2CompletedTreatmentBreast Cancer / Neutropenia1somestatusstop reasonjust information to hide
2CompletedTreatmentNeutropenia1somestatusstop reasonjust information to hide
2Not Yet RecruitingPreventionColorectal Cancer / Pancreatic Cancer1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous20 mg/1mL
Injection, solutionSubcutaneous20 mg
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Stimulator
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: RYZNEUTA® (efbemalenograstim alfa-vuxw) injection, for subcutaneous use I [Link]
  2. Efbemalenograstim alfa, a long-acting granulocyte colony-stimulating factor, a novel dimeric G-CSF Fc fusion protein for reducing the risk of febrile neutropenia following chemotherapy [Link]

Drug created at November 30, 2023 22:19 / Updated at January 07, 2024 09:46