NAV

Apadamtase alfa

Identification

Summary

Apadamtase alfa is a recombinant human ADAMTS13 for enzyme replacement therapy in patients with congenital thrombotic thrombocytopenic purpura.

Brand Names
Adzynma
Generic Name
Apadamtase alfa
DrugBank Accession Number
DB15164
Background

Thrombotic thrombocytopenic purpura (TTP) is a rare blood clotting disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and various degrees of organ damage.2 It may be inherited (congenital TTP; cTTP) or acquired due to autoantibodies (immune-mediated TTP; iTTP), although cTTP accounts for <5% of all cases of TTP.2 Patients with cTTP have a severe deficiency of a plasma metalloproteinase called ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), which is responsible for cleaving large von Willebrand factor multimers and preventing the formation of microthrombi - this deficiency in ADAMTS13 is responsible for the microangiopathic complications associated with cTTP.2 Standard therapy for cTTP involves prophylactic plasma infusions to supplement insufficient ADAMTS13 plasma levels.1

Apadamtase alfa, sold under the brand name Adzynma (ADAMTS13, recombinant-krhn), was approved by the FDA in November 2023 for use as an enzyme replacement therapy in patients with cTTP.4

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
>SUBUNIT_1
AAGGILHLELLVAVGPDVFQAHQEDTERYVLTNLNIGAELLRDPSLGAQFRVHLVKMVIL
TEPEGAPNITANLTSSLLSVCGWSQTINPEDDTDPGHADLVLYITRFDLELPDGNRQVRG
VTQLGGACSPTWSCLITEDTGFDLGVTIAHEIGHSFGLEHDGAPGSGCGPSGHVMASDGA
APRAGLAWSPCSRRQLLSLLSAGRARCVWDPPRPQPGSAGHPPDAQPGLYYSANEQCRVA
FGPKAVACTFAREHLDMCQALSCHTDPLDQSSCSRLLVPLLDGTECGVEKWCSKGRCRSL
VELTPIAAVHGRWSSWGPRSPCSRSCGGGVVTRRRQCNNPRPAFGGRACVGADLQAEMCN
TQACEKTQLEFMSQQCARTDGQPLRSSPGGASFYHWGAAVPHSQGDALCRHMCRAIGESF
IMKRGDSFLDGTRCMPSGPREDGTLSLCVSGSCRTFGCDGRMDSQQVWDRCQVCGGDNST
CSPRKGSFTAGRAREYVTFLTVTPNLTSVYIANHRPLFTHLAVRIGGRYVVAGKMSISPN
TTYPSLLEDGRVEYRVALTEDRLPRLEEIRIWGPLQEDADIQVYRRYGEEYGNLTRPDIT
FTYFQPKPRQAWVWAAVRGPCSVSCGAGLRWVNYSCLDQARKELVETVQCQGSQQPPAWP
EACVLEPCPPYWAVGDFGPCSASCGGGLRERPVRCVEAQGSLLKTLPPARCRAGAQQPAV
ALETCNPQPCPARWEVSEPSSCTSAGGAGLALENETCVPGADGLEAPVTEGPGSVDEKLP
APEPCVGMSCPPGWGHLDATSAGEKAPSPWGSIRTGAQAAHVWTPAAGSCSVSCGRGLME
LRFLCMDSALRVPVQEELCGLASKPGSRREVCQAVPCPARWQYKLAACSVSCGRGVVRRI
LYCARAHGEDDGEEILLDTQCQGLPRPEPQEACSLEPCPPRWKVMSLGPCSASCGLGTAR
RSVACVQLDQGQDVEVDEAACAALVRPEASVPCLIADCTYRWHVGTWMECSVSCGDGIQR
RRDTCLGPQAQAPVPADFCQHLPKPVTVRGCWAGPCVGQGTPSLVPHEEAAAPGRTTATP
AGASLEWSQARGLLFSPAPQPRRLLPGPQENSVQSSACGRQHLEPTGTIDMRGPGQADCA
VAIGRPLGEVVTLRVLESSLNCSAGDMLLLWGRLTWRKMCRKLLDMTFSSKTNTLVVRQR
CGRPGGGVLLRYGSQLAPETFYRECDMQLFGPWGEIVSPSLSPATSNAGGCRLFINVAPH
ARIAIHALATNMGAGTEGANASYILIRDTHSLRTTAFHGQQVLYWESESSQAEMEFSEGF
LKAQASLRGQYWTLQSWVPEMQDPQSWKGKEGT
References:
  1. NIH Inxight Drugs: Apadamtase alfa [Link]
Download FASTA Format
Synonyms
  • ADAMTS13, recombinant-krhn
  • Apadamtase alfa
  • Metalloproteinase ADAMTS13 (human recombinant BAX930)
  • rADAMTS-13
  • Recombinant disintegrin and metalloprotease with thrombospondin type 1 motifs
  • Recombinant human adamts13
External IDs
  • BAX-930
  • BAX930
  • SHP-655
  • SHP655
  • TAK-755
  • TAK755
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Pharmacology

Indication

Recombinant human ADAMTS13 is indicated for prophylactic or on-demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).3

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofCongenital thrombotic thrombocytopenic purpura•••••••••••••••••• ••••••••••••••••••• ••••••• •••••••••••• ••• ••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

A plasma ADAMTS13 activity of less than 10 IU/dL (often referred to as 10% of normal ADAMTS13 activity) is a hallmark of cTTP.2 Following the intravenous administration of 40 IU/kg of rADAMTS13, the mean duration of time for which ADAMTS13 activity remained above 10% was 5.3 days.3 Surrogate measures of von Willebrand factor platelet binding activity showed transient decreases of 15-25% from baseline for 1 or 2 days following intravenous administration.3

Mechanism of action

Congenital thrombotic thrombocytopenic purpura (cTTP) can be caused by a severe deficiency of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13).2 ADAMTS13 is a plasma zinc metalloprotease that regulates the activity of von Willebrand factor (VWF) by cleaving large and ultra-large VWF multimers to smaller units, reducing the platelet binding properties of VWF and its subsequent formation of microthrombi.3

Adzynma (ADAMTS13, recombinant-krhn) is a recombinant form of endogenous ADAMTS13. It is used as an enzyme replacement therapy in patients with cTTP and serves to partially restore ADAMTS13 activity in order to prevent thromboses.3

TargetActionsOrganism
Avon Willebrand factor
cleavage
Humans
Absorption

The average (Cave) and maximum (Cmax) serum concentrations of rADAMTS13 following intravenous administration of 40 IU/kg were 0.30 IU/mL and 1.15 IU/mL, respectively.3 The AUC0-inf and AUC0-168h were 57.6 IU.h/mL and 57.2 IU.h/mL, respectively.3

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

As with other therapeutic proteins, the rADAMTS13 is likely degraded via catabolic processes to smaller peptides and amino acids.

Route of elimination

Not Available

Half-life

Following the intravenous administration of 40 IU/kg of rADAMTS13, the mean half-life (t1/2) is 47.8 hours.3 The mean residence time (MRT0-inf) is 63.8 hours.3

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

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.
Not Available
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdzynmaInjection, powder, lyophilized, for solution; Kit500 [iU]/1[iU]IntravenousTakeda Pharmaceuticals America, Inc.2023-11-09Not applicableUS flag
AdzynmaInjection, powder, lyophilized, for solution; Kit1500 [iU]/1[iU]IntravenousTakeda Pharmaceuticals America, Inc.2023-11-09Not 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
U5SFU33XUX
CAS number
2086325-24-6

References

General References
  1. Zheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, Matsumoto M, Mustafa RA, Pai M, Rock G, Russell L, Tarawneh R, Valdes J, Peyvandi F: ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-2502. doi: 10.1111/jth.15010. Epub 2020 Sep 11. [Article]
  2. Zheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, Matsumoto M, Mustafa RA, Pai M, Rock G, Russell L, Tarawneh R, Valdes J, Peyvandi F: ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2486-2495. doi: 10.1111/jth.15006. Epub 2020 Sep 11. [Article]
  3. FDA Approved Drug Products: Adzynma (ADAMTS13, recombinant-krhn) lyophilized powder for intravenous injection [Link]
  4. FDA Press Announcement: FDA Approves First Treatment for Patients with Rare Inherited Blood Clotting Disorder [Link]
RxNav
2670285

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingPreventionThrombotic Thrombocytopenic Purpura (TTP)1
3RecruitingTreatmentThrombotic Thrombocytopenic Purpura (TTP)1
2CompletedTreatmentAcquired Thrombotic Thrombocytopenic Purpura (aTTP)1
2RecruitingTreatmentThrombotic Thrombocytopenic Purpura (TTP)1
1CompletedTreatmentCoronavirus Disease 2019 (COVID‑19) / Sickle Cell Disease (SCD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solution; kitIntravenous1500 [iU]/1[iU]
Injection, powder, lyophilized, for solution; kitIntravenous500 [iU]/1[iU]
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Details1. von Willebrand factor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Cleavage
Curator comments
Recombinant ADAMTS13 is a plasma zinc metalloprotease that regulates the activity of von Willebrand factor (VWF) by cleaving large and ultra-large VWF multimers to smaller units.
General Function
Protein n-terminus binding
Specific Function
Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surf...
Gene Name
VWF
Uniprot ID
P04275
Uniprot Name
von Willebrand factor
Molecular Weight
309261.83 Da
References
  1. FDA Approved Drug Products: Adzynma (ADAMTS13, recombinant-krhn) lyophilized powder for intravenous injection [Link]

Drug created at May 20, 2019 14:55 / Updated at November 24, 2023 04:34