Identification

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Name
Albutrepenonacog alfa
Accession Number
DB13884
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Blood factors / Fusion proteins
Description

Albutrepenonacog alfa (rIX-RFP) is a recombinant fusion protein that links a recombinant coagulation factor IX (rFIX) with a recombinant human albumin (rAlbumin).1 It was developed by CSL Behring Canada, Inc and approved by Health Canada on April 26, 2017. It was also approved by FDA and EMA in 2016. It is currently marketed in the forms of 250, 500, 1000 and 2000 IU/vial.5

Protein structure
Db13884
Protein chemical formula
C5077N7846O1588PS67
Protein average weight
125000.0 Da
Sequences
>>Albutrepenonacog alfa<<<<
YNSGKLEEFVQGNLERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGG
SCKDDINSYECWCPFGFEGKNCELDVTCNIKNGRCEQFCKNSADNKVVCSCTEGYRLAEN
QKSCEPAVPFPCGRVSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTR
VVGGEDAKPGQFPWQVVLNGKVDAFCGGSIVNEKWIVTAAHCVETGVKITVVAGEHNIEE
TEHTEQKRNVIRIIPHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFL
KFGSGYVSGWGRVFHKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDS
CQGDSGGPHVTEVEGTSFLTGIISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLTPVSQT
SKLTRAETVFPDVDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVT
EFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKD
DNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTE
CCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAE
FAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKS
HCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLL
RLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNAL
LVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKT
PVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQT
ALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL
Download FASTA Format
Synonyms
  • Coagulation factor IX (recombinant), albumin fusion protein
  • Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rIX-FP)
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IdelvionInjection, powder, for solution1000 IUIntravenousCsl Behring2016-05-11Not applicableEu
Idelvion3500 [iU]/5mLIntravenousCSL Behring Lengnau AG2018-05-30Not applicableUs
IdelvionInjection, powder, for solution500 IUIntravenousCsl Behring2016-05-11Not applicableEu
Idelvion2000 [iU]/5mLIntravenousCSL Behring Lengnau AG2016-03-04Not applicableUs
Idelvion500 [iU]/2.5mLIntravenousCSL Behring Lengnau AG2016-03-04Not applicableUs
IdelvionInjection, powder, for solution240 IUIntravenousCsl Behring2016-05-11Not applicableEu
Idelvion1000 [iU]/2.5mLIntravenousCSL Behring Lengnau AG2016-03-04Not applicableUs
Idelvion250 [iU]/2.5mLIntravenousCSL Behring Lengnau AG2016-03-04Not applicableUs
IdelvionKit; Powder, for solution3500 unitIntravenousCsl BehringNot applicableNot applicableCanada
IdelvionInjection, powder, for solution2000 IUIntravenousCsl Behring2016-05-11Not applicableEu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

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Categories
UNII
A57KX1VL5P
CAS number
1357448-54-4

Pharmacology

Indication

Under the EMA and FDA, rIX-RFP is indicated in the treatment of hemophilia B.6 For Health Canada, rIX-FRP is also indicated to prevent or reduce bleeding episodes.5

Hemophilia B is the second most common type of hemophilia. It is a rare inherited bleeding disorder caused by reduced or absent levels of factor IX (FIX). The FIX is a vitamin K-dependent plasma protease that when activated is involved in the blood coagulation cascade.2 The hemophilia B is caused by mutations in the FIX gene which can cause different phenotypes. The severe form is characterized by the presence of spontaneous and recurring bleeds into the joints and muscles and excessive bleeding after trauma or surgery.3

Associated Conditions
Pharmacodynamics

Clinical trials with rIX-RFP in patients with moderately to severe hemophilia B demonstrated a lower annualized spontaneous, total and joint bleeding rates. It was also efficient against bleeding episodes and maintenance of hemostasis in the perioperative setting when compared with on-demand treatment. The administration of rIX-RFP presented no reports of inhibitor development.1

Mechanism of action

The current therapies against hemophilia B are hampered by the short half-life of the replacement FIX therapy.1 Thus, to solve this problem, in rIX-RFP there is the fusion of rFIX with rAlbumin which presents a much longer half-life and it does not present interactions with the immune system.1

The administration of rIX-RFP increases the plasma concentration of FIX, thus addressing the coagulation deficiency of the patient. rIX-RFP is able to circulate in the plasma as an intact zymogen thanks to the pH-dependent binding to FcRn which is a normal protection pathway from lysosomal degradation of albumin. When the FIX is needed, rAlbumin is cleaved by the same proteases that activate the FIX.1

TargetActionsOrganism
ACoagulation factor X
activator
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

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Additional Data Available
Blackbox Warnings

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Absorption

rIX-RFP absorption is very rapid as it is directly administered intravenously. In clinical trials, the maximum plasma concentration, area under the curve and mean residence time are reported to be approximately 55 IU/dL, 5500 IU.h/dL and 125 hours respectively.1

Volume of distribution

The reported volume of distribution for rIX-RFP according to phase I/II and III clinical trials is 95 ml/kg.4

Protein binding

This pharmacokinetic value is not relevant as this drug is part of the plasma proteins.

Metabolism

The metabolism of rIX-RFP is not relevant as it is a recombinant protein and it is thought to be metabolized to peptides and amino acids.7

Route of elimination

rIX-RFP is mainly eliminated in the urine. In preclinical studies, the distribution of urine and feces 240 hours post administration corresponded to 72.9% and 4.3% of the administered dose respectively. The elimination on the first 24 hours in urine and feces only corresponded to the 39.9% and 0.92% of the dose.7

Half life

The fusion of the rFIX with rAlbumin prolongs the elimination half-life of rIX-RFP in the circulation. The reported half-life in clinical trials is 92 hours.1

Clearance

In clinical trials, the weight-adjusted clearance in children and adults is reported to be 1.1 and 0.9 ml/h/kg.1

Toxicity

rIX-RFP is very well tolerated.1Mutaginicity trials were performed and they confirmed an absent mutagenic potential.5Fertility studies have not been performed. Developmental studies are not of major importance as there is a very low rate of incidence of hemophilia B in females.

Affected organisms
  • Humans
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
(R)-warfarinThe therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with (R)-warfarin.
(S)-WarfarinThe therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with (S)-Warfarin.
4-hydroxycoumarinThe therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with 4-hydroxycoumarin.
AbacavirAbacavir may decrease the excretion rate of Albutrepenonacog alfa which could result in a higher serum level.
AbciximabThe therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Abciximab.
AcarboseAcarbose may decrease the excretion rate of Albutrepenonacog alfa which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Albutrepenonacog alfa which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Albutrepenonacog alfa which could result in a higher serum level.
AcenocoumarolThe therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Albutrepenonacog alfa which could result in a higher serum level.
Additional Data Available
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    Extended Description

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  • Severity
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Food Interactions
Not Available

References

General References
  1. Lyseng-Williamson KA: Coagulation Factor IX (Recombinant), Albumin Fusion Protein (Albutrepenonacog Alfa; Idelvion((R))): A Review of Its Use in Haemophilia B. Drugs. 2017 Jan;77(1):97-106. doi: 10.1007/s40265-016-0679-8. [PubMed:27988873]
  2. Nazeef M, Sheehan JP: New developments in the management of moderate-to-severe hemophilia B. J Blood Med. 2016 Apr 1;7:27-38. doi: 10.2147/JBM.S81520. eCollection 2016. [PubMed:27099538]
  3. Goodeve AC: Hemophilia B: molecular pathogenesis and mutation analysis. J Thromb Haemost. 2015 Jul;13(7):1184-95. doi: 10.1111/jth.12958. Epub 2015 May 18. [PubMed:25851415]
  4. Morfini M: Pharmacokinetic drug evaluation of albutrepenonacog alfa (CSL654) for the treatment of hemophilia. Expert Opin Drug Metab Toxicol. 2016 Oct 2:1-7. doi: 10.1080/17425255.2016.1240168. [PubMed:27677190]
  5. Health Canada monograph [Link]
  6. EMA Product report [Link]
  7. PMDA report on the deliberation [Link]
External Links
PubChem Substance
347911453
AHFS Codes
  • 20:28.16 — Hemostatics
FDA label
Download (253 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Not Yet RecruitingTreatmentHemophilia1
Not AvailableRecruitingNot AvailableHemophilia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous1000 IU
Injection, powder, for solutionIntravenous2000 IU
Injection, powder, for solutionIntravenous240 IU
Injection, powder, for solutionIntravenous500 IU
Kit; powder, for solutionIntravenous250 unit
Kit; powder, for solutionIntravenous3500 unit
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Activator
General Function
Serine-type endopeptidase activity
Specific Function
Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
Gene Name
F10
Uniprot ID
P00742
Uniprot Name
Coagulation factor X
Molecular Weight
54731.255 Da
References
  1. Lyseng-Williamson KA: Coagulation Factor IX (Recombinant), Albumin Fusion Protein (Albutrepenonacog Alfa; Idelvion((R))): A Review of Its Use in Haemophilia B. Drugs. 2017 Jan;77(1):97-106. doi: 10.1007/s40265-016-0679-8. [PubMed:27988873]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity
Specific Function
Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
Gene Name
F8
Uniprot ID
P00451
Uniprot Name
Coagulation factor VIII
Molecular Weight
267007.42 Da
References
  1. Lyseng-Williamson KA: Coagulation Factor IX (Recombinant), Albumin Fusion Protein (Albutrepenonacog Alfa; Idelvion((R))): A Review of Its Use in Haemophilia B. Drugs. 2017 Jan;77(1):97-106. doi: 10.1007/s40265-016-0679-8. [PubMed:27988873]

Drug created on September 07, 2017 13:20 / Updated on November 22, 2019 04:24