Vilobelimab

Identification

Summary

Vilobelimab is an antibody directed against anti-human complement factor 5a is used to treat COVID-19 in adults for emergency use.

Generic Name
Vilobelimab
DrugBank Accession Number
DB16416
Background

Vilobelimab is a chimeric monoclonal immunoglobulin G4 (IgG4) antibody that binds to the soluble form of human C5a with high affinity. It consists of mouse anti-human complement factor 5a (C5a) monoclonal binding sites (variable regions of heavy and light chain regions) and human gamma 4 heavy chain and light kappa chain constant regions.6 In April 2023, the FDA issued an emergency use authorization (EUA) for vilobelimab for the treatment of COVID-19 in hospitalized adults requiring mechanical ventilation or artificial life support. The drug is not yet fully approved for this condition.7

Type
Biotech
Groups
Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6456H9976N1716O2054S44
Protein Average Weight
149000.0 Da (approximate)
Sequences
>Vilobelimab heavy chain
QVQLQQSGPQLVRPGTSVKISCKASGYSFTTFWMDWVKQRPGQGLEWIGRIDPSDSESRL
DQRFKDRATLTVDKSSSTVYMQLSSPTSEDSAVYYCARGNDGYYGFAYWGQGTLVTVSSA
STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN
QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN
VFSCSVMHEALHNHYTQKSLSLSLGK
>Vilobelimab light chain
DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMKWYQQKPGQPPKLLIYAASNLQS
GIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPYTFGGGTKLEIKRTVAAPSVF
IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS
STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. KEGG DRUG: Vilobelimab [Link]
Download FASTA Format
Synonyms
  • IFX-1
  • Vilobelimab
External IDs
  • CACP 29
  • CaCP29
  • IFX-1

Pharmacology

Indication

Vilobelimab is used for emergency use to treat coronavirus disease 19 (COVID-19) in hospitalized adults when initiated within 48 hours of receiving invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). However, vilobelimab is not FDA-approved for this use.6

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofCoronavirus disease 2019 (covid‑19)•••••••••••••••••••••••••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Vilobelimab is believed to attenuate inflammation and associated tissue damage by binding to complement factor 5a (C5a).6 In clinical trials of patients with severe COVID-19 pneumonia requiring IMV or ECMO, vilobelimab reduced the median concentrations of C5a from the baseline plasma concentrations of 118.29 ng/mL to 14.53 ng/mL: this effect persisted up to Day 30 after the initiation of treatment. However, the direct clinical relevance of C5a plasma concentration reduction is unclear.6

Mechanism of action

The complement system is a critical innate immune response against pathogens.4 Activation of the complement cascade results in proteolytic cleavage of the complement factor C5, generating C5a and C5b.4 C5a is a potent anaphylatoxin that binds to the C5a receptor to initiate an inflammatory cascade. The C5a/C5aR1 signalling pathway promotes enhanced vascular permeability, coagulation, proinflammatory cytokine release, and recruitment and activation of neutrophils and other myeloid cells.5,6 Ultimately, C5a also initiates neutrophil-driven tissue damage.4,5 Complement activation and high levels of C5a have been implicated in various inflammatory conditions,5 such as septic shock,4 antineutrophilic cytoplasmic antibody (ANCA) vasculitis,2 and viral infections such as avian influenza A (H7N9) virus infection and Coronavirus disease (COVID-19).1,3

The complement system can be activated through three pathways: classical, lectin, and alternative pathways. The lectin pathway is triggered by binding of either mannose-binding lectin protein (MBL) or ficolin to pathogens, such as bacterial or fungal carbohydrate structures and proteins.5 Experimental studies suggest that the SARS-CoV-2 virus nucleocapsid protein can bind to the mannan-binding lectin serine protease 2, thereby activating the downstream complement pathway and generating C5a. Because high levels of C5a have been identified in patients with severe COVID-19, C5a was suggested as a key mediator of acute respiratory distress syndrome and thrombotic microangiopathy associated with COVID-19.3 Vilobelimab is a chimeric monoclonal IgG4-kappa antibody that binds to complement factor 5a (C5a) with a dissociation constant of 9.6pM and blocks its interaction with the C5a receptor.6

TargetActionsOrganism
UComplement C5
inhibitor
Humans
Absorption

In healthy subjects who received a single intravenous infusion of vilobelimab ranging from 2 mg/kg to 4 mg/kg, the Cmax showed dose proportionality while the AUC showed greater-than-dose proportionality.6

Pre-dose plasma samples were collected in patients with severe COVID-19 pneumonia requiring IMV or ECMO. Following intravenous infusion of vilobelimab 800 mg on Days 1, 2, and 4, the pre-dose geometric mean (geometric CV%) plasma concentration of vilobelimab on Day 8 was 137.9 µg/mL (51%).6

Volume of distribution

No information is available.

Protein binding

No information is available.

Metabolism

As with other monoclonal antibodies, vilobelimab is expected to undergo nonspecific degradation into small peptides and individual amino acids.

Route of elimination

No information is available.

Half-life

The elimination half-life of vilobelimab following a 4 mg/kg single intravenous dose in healthy subjects was 95 hours.6

Clearance

No information is available.

Adverse Effects
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Toxicity

There is no information regarding the acute toxicity or overdose of vilobelimab.

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 Vilobelimab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Vilobelimab.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Vilobelimab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Vilobelimab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Vilobelimab.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
GohibicInjection10 mg/1mLIntravenousInflaRx GmbH2023-04-04Not 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
Not Available

Chemical Identifiers

UNII
F5T0RF9ZJA
CAS number
2250440-41-4

References

General References
  1. Sun S, Zhao G, Liu C, Fan W, Zhou X, Zeng L, Guo Y, Kou Z, Yu H, Li J, Wang R, Li Y, Schneider C, Habel M, Riedemann NC, Du L, Jiang S, Guo R, Zhou Y: Treatment with anti-C5a antibody improves the outcome of H7N9 virus infection in African green monkeys. Clin Infect Dis. 2015 Feb 15;60(4):586-95. doi: 10.1093/cid/ciu887. Epub 2014 Nov 27. [Article]
  2. Jayne D: Complement inhibition in ANCA vasculitis. Nephrol Ther. 2019 Nov;15(6):409-412. doi: 10.1016/j.nephro.2019.04.001. Epub 2019 Oct 17. [Article]
  3. Vlaar APJ, de Bruin S, Busch M, Timmermans SAMEG, van Zeggeren IE, Koning R, Ter Horst L, Bulle EB, van Baarle FEHP, van de Poll MCG, Kemper EM, van der Horst ICC, Schultz MJ, Horn J, Paulus F, Bos LD, Wiersinga WJ, Witzenrath M, Rueckinger S, Pilz K, Brouwer MC, Guo RF, Heunks L, van Paassen P, Riedemann NC, van de Beek D: Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial. Lancet Rheumatol. 2020 Dec;2(12):e764-e773. doi: 10.1016/S2665-9913(20)30341-6. Epub 2020 Sep 28. [Article]
  4. Bauer M, Weyland A, Marx G, Bloos F, Weber S, Weiler N, Kluge S, Diers A, Simon TP, Lautenschlager I, Grundling M, Jaschinski U, Simon P, Nierhaus A, Moerer O, Reill L, Jorres A, Guo R, Loeffler M, Reinhart K, Riedemann N: Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock-A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study). Crit Care Explor. 2021 Nov 17;3(11):e0577. doi: 10.1097/CCE.0000000000000577. eCollection 2021 Nov. [Article]
  5. Guo RF, Ward PA: Role of C5a in inflammatory responses. Annu Rev Immunol. 2005;23:821-52. doi: 10.1146/annurev.immunol.23.021704.115835. [Article]
  6. FDA EUA Drug Products: GOHIBIC (vilobelimab) injection, for intravenous use [Link]
  7. FDA: FDA authorizes Gohibic (vilobelimab) injection for the treatment of COVID-19 [Link]
RxNav
2639620
Wikipedia
Vilobelimab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentPyoderma Gangrenosum1
2Active Not RecruitingTreatmentSsc1
2CompletedTreatmentC.Surgical Procedure; Cardiac / Systemic Inflammatory Response Syndrome (SIRS)1
2CompletedTreatmentGranulomatosis With Polyangiitis / Microscopic Polyangiitis (MPA)1
2CompletedTreatmentHidradenitis Suppurativa (HS)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous10 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
C5 is a precursor of C5a anaphylatoxin and C5b. Vilobelimab is an inhibitor of C5a.
General Function
Receptor binding
Specific Function
Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C...
Gene Name
C5
Uniprot ID
P01031
Uniprot Name
Complement C5
Molecular Weight
188303.705 Da
References
  1. Vlaar APJ, de Bruin S, Busch M, Timmermans SAMEG, van Zeggeren IE, Koning R, Ter Horst L, Bulle EB, van Baarle FEHP, van de Poll MCG, Kemper EM, van der Horst ICC, Schultz MJ, Horn J, Paulus F, Bos LD, Wiersinga WJ, Witzenrath M, Rueckinger S, Pilz K, Brouwer MC, Guo RF, Heunks L, van Paassen P, Riedemann NC, van de Beek D: Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial. Lancet Rheumatol. 2020 Dec;2(12):e764-e773. doi: 10.1016/S2665-9913(20)30341-6. Epub 2020 Sep 28. [Article]
  2. Riedemann NC, Habel M, Ziereisen J, Hermann M, Schneider C, Wehling C, Kirschfink M, Kentouche K, Guo R: Controlling the anaphylatoxin C5a in diseases requires a specifically targeted inhibition. Clin Immunol. 2017 Jul;180:25-32. doi: 10.1016/j.clim.2017.03.012. Epub 2017 Mar 30. [Article]
  3. FDA EUA Drug Products: GOHIBIC (vilobelimab) injection, for intravenous use [Link]

Drug created at December 23, 2020 18:12 / Updated at April 15, 2023 22:28