Sutimlimab

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:

NIH Inxight: Sutimlimab [Link]

Download FASTA Format

Synonyms

Humanized IgG4 monoclonal antibody against total complement component 1, subcomponent s
Sutimlimab

External IDs

BIVV-009
BIVV009
TNT-009
TNT009

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Pharmacology

Indication

Sutimlimab is indicated to treat hemolysis in adults with cold agglutinin disease (CAD) ⁸ and decrease the need for red blood cell transfusion in these patients.^4,6

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Hemolysis		••••••••••••	•••••
Prevention of	Hemolysis		••••••••••••	•••••		•••••••••

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.

Target	Actions	Organism
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.

Drug	Interaction
Integrate drug-drug interactions in your software
Abatacept	The risk or severity of adverse effects can be increased when Abatacept is combined with Sutimlimab.
Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Sutimlimab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Sutimlimab.
Adenovirus type 7 vaccine live	The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Sutimlimab.
Aducanumab	The risk or severity of adverse effects can be increased when Aducanumab is combined with Sutimlimab.

Food Interactions

Not Available

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Enjaymo	Injection, solution	50 mg/ml	Intravenous	Sanofi B.V.	2023-02-08	Not applicable
Enjaymo	Injection, solution, concentrate	50 mg/1mL	Intravenous	Bioverativ Therapeutics Inc.	2022-02-04	Not applicable
Enjaymo	Injection, solution	50 mg/ml	Intravenous	Sanofi B.V.	2023-02-08	Not applicable

Chemical Identifiers

UNII: GNWE7KJ995
CAS number: 2049079-64-1

References

General References

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]
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]
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]
FDA Approved Drug Products: Enjaymo (sutimlimab-jome) injection for intravenous use [Link]
National Organization for Rare Disorders: Cold Agglutinin Disease [Link]
EMA Approved Drug Products: Enjaymo (Sutimlimab) Intravenous Injection [Link]
Sanofi: Press Release: European Commission approves Enjaymo® (sutimlimab) for treatment of hemolytic anemia in adult patients with cold agglutinin disease [Link]
FDA Approved Drug Products: ENJAYMO (sutimlimab-jome) injection, for intravenous use (January 2023) [Link]

External Links

RxNav: 2591404
Wikipedia: Sutimlimab

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
3	Completed	Treatment	Cold Agglutinin Disease (CAD)	3
1	Completed	Treatment	Immune Thrombocytopenia (ITP)	1
Not Available	Recruiting	Not Available	Cold Agglutinin Disease (CAD) / Cold Agglutinin Syndrome (CAS)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution	Intravenous	50 mg/ml
Injection, solution, concentrate	Intravenous	50 mg/1mL

Prices

Not Available

Patents

Not Available

Properties

State: Liquid
Experimental Properties: Not Available

Targets

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Details1. Complement C1s subcomponent

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

FDA Approved Drug Products: Enjaymo (sutimlimab-jome) injection for intravenous use [Link]

Drug created at May 20, 2019 14:40 / Updated at November 20, 2023 20:11

Sutimlimab

Identification

References:

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References