Caplacizumab

Explore a selection of our essential drug information below, or:

Unlock enhanced features & extensive drug insights, including detailed interaction data & regulatory status. Create a free account.

SUBSCRIBERECOMMENDED FOR PHARMA

Explore the full scope of our drug knowledge tailored for pharmaceutical research needs in our data library. Learn more.

Identification

Summary

Caplacizumab is a von Willebrand factor (vWF)-directed antibody fragment used to treat acquired thrombotic thrombocytopenic purpura (aTTP).

Brand Names

Cablivi

Generic Name

Caplacizumab

DrugBank Accession Number

DB06081

Background

Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019,⁶ and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression.¹

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Monoclonal antibody (mAb)

Protein Structure

Protein Chemical Formula: C₁₂₁₃H₁₈₉₁N₃₅₇O₃₈₀S₁₀
Protein Average Weight: 27880.0 Da

Sequences

>>Caplacizumab<<<
EVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVAAISRTGGSTYY
PDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVRTLPSEYTFWGQ
GTQVTVSSAAAEVQLVESGGGLVQPGGSLRLSCAASGRTFSYNPMGWFRQAPGKGRELVA
AISRTGGSTYYPDSVEGRFTISRDNAKRMVYLQMNSLRAEDTAVYYCAAAGVRAEDGRVR
TLPSEYTFWGQGTQVTVSS

References:

Cablivi (caplacizumab) EMA label [File]

Download FASTA Format

Synonyms

Caplacizumab
caplacizumab-yhdp

External IDs

ALX 0081
ALX 0681
ALX-0081

Unlock the secrets to drugging the undruggable

Discover how groundbreaking research is turning "undruggable" targets into therapeutic opportunities.

Download eBook

Unlock the secrets to drugging the undruggable

Download eBook

Pharmacology

Indication

Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older.^1,6

aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications.³

Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn.¹

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used as adjunct in combination to treat	Acquired thrombotic thrombocytopenic purpura		••••••••••••	•••••		•••••••••
Treatment of	Acquired thrombotic thrombocytopenic purpura (attp)		••••••••••••	••••••••••• •••••• •••••••	••••••••••••••••• •••••••••• •••••• ••••••••• •••••• • •• ••	•••••••••• ••••••• ••• ••••••••

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

In vitro studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex.¹

In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP¹ as well as a significant reduction in the median time to response of about 39%.⁴ However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation.²

The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment.⁶

Mechanism of action

Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific.[5305] The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation.¹

Target	Actions	Organism
Uvon Willebrand factor	Not Available	Humans

Absorption

After intravenous administration of caplacizumab, the pharmacokinetic profile is non-linear and to follow a non-compartmental model as the pharmacokinetic profile of this drug is dependent on the expression of von Willebrand factor. After administration, caplacizumab is rapidly absorbed with a dose-dependent behavior. The peak concentration was reached after 6-7 hours¹ and it presents a very high bioavailability reaching approximately 90%.¹⁰

The subcutaneous administration of a dose of 10 mg of caplacizumab produced a peak concentration of 528 ng/ml and an AUC of 7951 ng.h/ml.⁸

Volume of distribution

The reported volume of distribution of caplacizumab is 6.33 L.¹

Protein binding

This antibody acts directly on plasma proteins and thus, this parameter is not significant for drug description.

Metabolism

Caplacizumab is degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.⁵

Route of elimination

The elimination of caplacizumab is divided between target-driven disposition which is driven by the binding to the von Willebrand factor and non-target disposition driven by the combination of catabolism and renal elimination.¹⁰

Half-life

The reported half-life is reported to be in the range of 16-27 hours.¹⁰

Clearance

As the elimination is highly divided among hepatic, target-driven and renal elimination, the calculation of the clearance rate is not significant for drug description.

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

Toxicity

Cases of overdose are represented by an increased risk of bleeding and in these cases, external administration of von Willebrand factor concentrate should be done.^Label

To this point, there have not been performed studies regarding the effect on fertility, genotoxicity, or carcinogenicity

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.

Drug	Interaction
Integrate drug-drug interactions in your software
Abciximab	The risk or severity of bleeding can be increased when Caplacizumab is combined with Abciximab.
Abrocitinib	The risk or severity of bleeding and thrombocytopenia can be increased when Caplacizumab is combined with Abrocitinib.
Aceclofenac	The risk or severity of bleeding can be increased when Aceclofenac is combined with Caplacizumab.
Acemetacin	The risk or severity of bleeding can be increased when Acemetacin is combined with Caplacizumab.
Acenocoumarol	The risk or severity of bleeding can be increased when Caplacizumab is combined with Acenocoumarol.

Food Interactions

No interactions found.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Cablivi	Injection, powder, for solution	10 mg	Intravenous; Subcutaneous	Ablynx N.V.	2021-01-12	Not applicable
Cablivi	Injection, powder, lyophilized, for solution; Kit	11 mg/1mL	Intravenous; Subcutaneous	Genzyme Corporation	2019-02-06	Not applicable
Cablivi	Injection, powder, for solution	10 mg	Intravenous; Subcutaneous	Ablynx N.V.	2021-01-12	Not applicable
Cablivi	Injection, powder, for solution	10 mg	Intravenous; Subcutaneous	Ablynx N.V.	2021-01-12	Not applicable
Cablivi	Kit; Powder, for solution	11 mg / vial	Intravenous; Subcutaneous	Sanofi Aventis	2020-09-04	Not applicable

Chemical Identifiers

UNII: 2R27AB6766
CAS number: 915810-67-2

References

General References

Duggan S: Caplacizumab: First Global Approval. Drugs. 2018 Oct;78(15):1639-1642. doi: 10.1007/s40265-018-0989-0. [Article]
Coppo P, Cuker A, George JN: Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine. Res Pract Thromb Haemost. 2018 Nov 16;3(1):26-37. doi: 10.1002/rth2.12160. eCollection 2019 Jan. [Article]
Peyvandi F, Scully M, Kremer Hovinga JA, Knobl P, Cataland S, De Beuf K, Callewaert F, De Winter H, Zeldin RK: Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2017 Jul;15(7):1448-1452. doi: 10.1111/jth.13716. Epub 2017 Jun 5. [Article]
Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knobl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D: Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2016 Feb 11;374(6):511-22. doi: 10.1056/NEJMoa1505533. [Article]
Tabrizi MA, Tseng CM, Roskos LK: Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006 Jan;11(1-2):81-8. doi: 10.1016/S1359-6446(05)03638-X. [Article]
FDA news [Link]
Guide to Pharmacology [Link]
Clinical trials [Link]
FDA Approved Drug Products: CABLIVI (caplacizumab-yhdp) injection [Link]
Cablivi (caplacizumab) EMA label [File]

External Links

RxNav: 2110604
Wikipedia: Caplacizumab

FDA label

Download (1.21 MB)

MSDS

Download (92 KB)

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

Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
Unlock 175K+ rows when you subscribe.View sample data
Not Available	Completed	Not Available	Immune-mediated Thrombocytopenic Purpura	1	somestatus	stop reason	just information to hide
Not Available	Not Yet Recruiting	Not Available	Immune Thrombotic Thrombocytopenia	1	somestatus	stop reason	just information to hide
Not Available	Recruiting	Not Available	Acquired Thrombotic Thrombocytopenic Purpura (aTTP)	2	somestatus	stop reason	just information to hide
Not Available	Recruiting	Not Available	Thrombotic Thrombocytopenic Purpura (TTP)	1	somestatus	stop reason	just information to hide
3	Active Not Recruiting	Treatment	Thrombotic Thrombocytopenic Purpura (TTP)	1	somestatus	stop reason	just information to hide

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Intravenous; Subcutaneous	10 mg
Injection, powder, for solution	Parenteral; Subcutaneous	10 MG
Injection, powder, lyophilized, for solution; kit	Intravenous; Subcutaneous	11 mg/1mL
Kit; powder, for solution	Intravenous; Subcutaneous	11 mg / vial
Injection, powder, for solution	Parenteral	10 mg/1ml
Injection, powder, lyophilized, for solution	Intravenous; Subcutaneous	10 mg

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	61 ºC (Fab fragment)	Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
boiling point (°C)	Fab fragment denaturates at 60 ºC	Arnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404
water solubility	Soluble	Acqua E. Can Caplacizumab be a potential first drug therapy for Thrombotic Thrombocytopenic Purpura?.
isoelectric point	6.6 - 7.2	Jin, et al. Electrophoresis. Sep;23(19):3385-91. (2002).

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. von Willebrand factor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General 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-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma
Specific Function: collagen binding
Gene Name: VWF
Uniprot ID: P04275
Uniprot Name: von Willebrand factor
Molecular Weight: 309261.83 Da

Drug created at November 18, 2007 18:29 / Updated at June 03, 2022 07:24

Caplacizumab

Identification

References:

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Clinical Trial & Rare Diseases Add-on Data Package

Pharmacoeconomics

Properties

Targets