Identification

Summary

Sutimlimab is a monoclonal antibody directed towards complement subunit C1s used to reduce the need for blood transfusion due to hemolysis in patients with cold agglutinin disease.

Brand Names
Enjaymo
Generic Name
Sutimlimab
DrugBank Accession Number
DB14996
Background

Cold agglutinin disease (CAD) is a type of autoimmune hemolytic anemia (AIHA) in which autoantibodies directed against red blood cell surface antigens cause hemolysis at low (3-4°C) temperatures.2,5 This cold subtype accounts for approximately 15-25% of all AIHA and is more common in the elderly.3,5 In approximately 90% of cases, patients develop immunoglobulin M (IgM) autoantibodies towards the I antigen on erythrocytes - these antibodies react optimally at 4°C and are therefore referred to as "cold agglutinin".1 Hemolysis in patients with CAD is driven by complement activation, which initiates a cascade that ultimately leads to both intra- and extravascular hemolysis.3 The most common presenting symptoms in patients with CAD are chronic anemia, acrocyanosis, and Raynaud phenomenon.3

Treatment options for patients with CAD are limited. In addition to non-pharmacological strategies, such as counseling patients to keep warm and the use of red blood cell transfusions, approximately 70% of patients require pharmacological treatment.3 Pharmacologic strategies have included the targeting of B-cells with agents like rituximab, as well as targeting of the complement system with drugs like eculizumab, an anti-C5 mAb, and pegcetacoplan, a novel inhibitor of C3.2 Notably, none of these agents are approved for use in the treatment of CAD.

Sutimlimab is a first-in-class humanized monoclonal antibody targeted at complement subunit C1s, which is responsible for activating the classic complement pathway.1 It received FDA approval in February 2022, under the brand name Enjamyo (sutimlimab-jome), becoming the first approved therapy for patients with CAD.5,1 Sutimlimab was also approved by the European Commission in November 2022.7

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6436H9934O2012N1700S46
Protein Average Weight
147000.0 Da
Sequences
>SUBUNIT_1
EVQLVESGGGLVKPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVATISSGGSHTYY
LDSVKGRFTISRDNSKNTLYLQMNSLRAEDTALYYCARLFTGYAMDYWGQGTLVTVSSAS
TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV
FSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_2
EVQLVESGGGLVKPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVATISSGGSHTYY
LDSVKGRFTISRDNSKNTLYLQMNSLRAEDTALYYCARLFTGYAMDYWGQGTLVTVSSAS
TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV
FSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_3
QIVLTQSPATLSLSPGERATMSCTASSSVSSSYLHWYQQKPGKAPKLWIYSTSNLASGVP
SRFSGSGSGTDYTLTISSLQPEDFATYYCHQYYRLPPITFGQGTKLEIKRTVAAPSVFIF
PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST
LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>SUBUNIT_4
QIVLTQSPATLSLSPGERATMSCTASSSVSSSYLHWYQQKPGKAPKLWIYSTSNLASGVP
SRFSGSGSGTDYTLTISSLQPEDFATYYCHQYYRLPPITFGQGTKLEIKRTVAAPSVFIF
PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST
LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. NIH Inxight: Sutimlimab [Link]
Download FASTA Format
Synonyms
  • Sutimlimab
External IDs
  • BIVV-009
  • BIVV009
  • TNT-009
  • TNT009

Pharmacology

Indication

Sutimlimab is indicated to decrease the need for red blood cell transfusion due to hemolysis in adult patients with cold agglutinin disease.4,6

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Following a single sutimlimab injection, >90% inhibition of the complement pathway was observed, and this inhibition was sustained when concentrations of sutimlimab were ≥100 mcg/mL.4

As sutimlimab can impair the complement-mediated immune response, patients requiring therapy should receive all appropriate vaccinations against encapsulated bacteria at least 2 weeks prior to its initiation.4 Patients undergoing treatment with sutimlimab are at a higher risk of serious infections, especially those caused by encapsulated bacteria such as Neisseria meningitides or Streptococcus pneumoniae, and should be monitored closely throughout therapy for evidence of developing or ongoing infections.4

Mechanism of action

Hemolysis associated with cold agglutinin disease is driven by the activation of the complement system.3 Cold agglutinins transiently bind erythrocytes as they circulate through cooler parts of the body (e.g. the extremities) - as they circulate back to warmer areas, C1q esterase activates C4 and C2, which generates C3 convertase, an enzyme which cleaves C3 into C3a and C3b.3 At this stage, the erythrocytes tagged with C3b can be sequestered by macrophages in the reticuloendothelial system, ultimately leading to extravascular hemolysis.3 Alternatively, C3b may be further cleaved into C3c and C3d - if complement activation continues past the C3 step, the membrane attack complex with C5b-C9 may form, which causes intravascular hemolysis.3

Sutimlimab is a humanized IgG4 monoclonal antibody targeted at the complement C1s subunit, a serine protease responsible for the activation of the classic complement pathway.1,4 By inhibiting the complement cascade at the level of C1s, sutimlimab prevents the deposition of complement opsinins on erythrocytes, thus preventing their eventual hemolysis.

TargetActionsOrganism
AComplement C1s subcomponent
inhibitor
antibody
Humans
Absorption

When administered at the approved weight-based recommended dosage, the exposure to sutimlimab increases proportionately with increasing dosage.4 Steady-state concentrations are achieved by week 7 of therapy.4

Volume of distribution

At steady-state, the volume of distribution of sutimlimab in patients with cold agglutinin disease was approximately 5.8 L.4

Protein binding

Not Available

Metabolism

As with other therapeutic proteins, sutimlimab likely undergoes catabolism to smaller peptides and amino acids.4

Route of elimination

Not Available

Half-life

At the approved recommended dosage, the terminal elimination half-life of sutimlimab is 21 days.4 The half-life of sutimlimab varies at different doses due to target-mediated drug disposition at lower concentrations.4

Clearance

At the approved recommended dosage, the clearance of sutimlimab is 0.14 L/day.4 The clearance of sutimlimab varies at different doses due to target-mediated drug disposition at lower concentrations.4

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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Sutimlimab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Sutimlimab.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Sutimlimab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Sutimlimab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Sutimlimab.
AmivantamabThe risk or severity of adverse effects can be increased when Sutimlimab is combined with Amivantamab.
AnifrolumabThe risk or severity of adverse effects can be increased when Anifrolumab is combined with Sutimlimab.
AnsuvimabThe risk or severity of adverse effects can be increased when Sutimlimab is combined with Ansuvimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Sutimlimab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Sutimlimab.
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Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EnjaymoInjection, solution, concentrate50 mg/1mLIntravenousBioverativ U.S. LLC.2022-02-04Not applicableUS flag

Categories

ATC Codes
L04AA55 — Sutimlimab
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 and other mammals

Chemical Identifiers

UNII
GNWE7KJ995
CAS number
2049079-64-1

References

General References
  1. Roth A, Barcellini W, D'Sa S, Miyakawa Y, Broome CM, Michel M, Kuter DJ, Jilma B, Tvedt THA, Fruebis J, Jiang X, Lin S, Reuter C, Morales-Arias J, Hobbs W, Berentsen S: Sutimlimab in Cold Agglutinin Disease. N Engl J Med. 2021 Apr 8;384(14):1323-1334. doi: 10.1056/NEJMoa2027760. [Article]
  2. Patriquin CJ, Pavenski K: O, wind, if winter comes ... will symptoms be far behind?: Exploring the seasonality (or lack thereof) and management of cold agglutinin disease. Transfusion. 2022 Jan;62(1):2-10. doi: 10.1111/trf.16765. Epub 2021 Dec 10. [Article]
  3. Gabbard AP, Booth GS: Cold Agglutinin Disease. Clin Hematol Int. 2020 Jul 17;2(3):95-100. doi: 10.2991/chi.k.200706.001. eCollection 2020 Sep. [Article]
  4. FDA Approved Drug Products: Enjaymo (sutimlimab-jome) injection for intravenous use [Link]
  5. National Organization for Rare Disorders: Cold Agglutinin Disease [Link]
  6. EMA Approved Drug Products: Enjaymo (Sutimlimab) Intravenous Injection [Link]
  7. Sanofi: Press Release: European Commission approves Enjaymo® (sutimlimab) for treatment of hemolytic anemia in adult patients with cold agglutinin disease [Link]
RxNav
2591404
Wikipedia
Sutimlimab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentCold Agglutinin Disease (CAD)1
3CompletedTreatmentCold Agglutinin Disease (CAD)2
1CompletedTreatmentImmune Thrombocytopenia (ITP)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous50 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
Yes
Actions
Inhibitor
Antibody
General Function
Serine-type endopeptidase activity
Specific Function
C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activat...
Gene Name
C1S
Uniprot ID
P09871
Uniprot Name
Complement C1s subcomponent
Molecular Weight
76683.905 Da
References
  1. FDA Approved Drug Products: Enjaymo (sutimlimab-jome) injection for intravenous use [Link]

Drug created at May 20, 2019 14:40 / Updated at November 28, 2022 16:20