Medical Drug Criteria (MDC)

Policy Num:       P1.001.013
Policy Name:     ENJAYMO^® (sutimlimab-jome)
Policy ID:          [P1.001.013] [Ac/L/ M+/ P+ ] 

Last Review:       September 22, 2025
Next Review:      September 20, 2026
 

Related MDC:NONE

ENJAYMO^® (sutimlimab-jome)

Summary

Sutimlimab-jome (Enjaymo) is a monoclonal antibody that inhibits the classical complement pathway by binding to complement protein component 1 subcomponent s (C1s). This inhibition ultimately prevents hemolysis in patients with cold agglutinin disease (CAD). Sutimlimab-jome (Enjaymo) is FDA-approved for the treatment of hemolysis in adults with cold agglutinin disease (CAD). FDA approval: Indicated for treatment of hemolysis in adults with CAD (02/2022; revised PI 02/2024). Mechanism: Targets C1s, preventing C3 activation and subsequent extravascular hemolysis. Clinical trials (CARDINAL, CADENZA): demonstrated rapid increase in hemoglobin, reduction in transfusion needs, and improvement in fatigue scores. Special notes: Vaccination against encapsulated bacteria (pneumococcal, meningococcal, Hib) required before initiation.

Objective

Ensure safe and medically necessary use of sutimlimab in CAD. Provide coverage guidance consistent with FDA label, NCCN recommendations, and payer standards. Standardize criteria for initiation, continuation, and exclusion.

Policy Statements

ENJAYMO (sutimlimab) is considered medically necessary for adult patients with CAD who meet all medical criteria specified under Required Medical Information.

Policy Guidelines

Authorization period: Initial approval up to 6 months.

Route/Site: Intravenous infusion.

Vaccination: Required against S. pneumoniae, N. meningitidis, H. influenzae type B ≥2 weeks prior, or prophylactic antibiotics if started earlier.

Exclusion: Not indicated for secondary CAD (infection, autoimmune disease, lupus, malignancy).

DOSAGE/ADMINISTRATION

• Vaccinate against encapsulated bacteria at least two weeks prior to treatment.

• Weight-based dosage weekly for two weeks then every two weeks:

For patients weighing 39 kg to less than 75 kg: 6,500 mg by intravenous infusion.

For patients weighing 75 kg or more: 7,500 mg by intravenous infusion

REQUIRED MEDICAL INFORMATION

Initial Therapy

1.    Initiation of sutimlimab-jome (Enjaymo) meets the definition of medical necessity when used to treat the following indications when the specific criteria are met: 

a.    Cold Agglutinin Disease (CAD)

i.    Diagnosis is confirmed by ALL of the following – documentation must be submitted: 

1.    Chronic hemolysis 

2.    Polyspecific direct antiglobulin test (DAT) 

3.    Monospecific DAT specific for C3d 

4.    Cold agglutinin titer greater than or equal to 64 at 4 degree Celsius

5.    IgG DAT less than or equal to 1+ 

ii.    Member has anemia with a hemoglobin less than the lower limit of normal

iii.    The member had an inadequate response, intolerance, or is not a candidate for rituximab 

iv.    ONE of the following: 

1.    Member has been vaccinated against encapsulated bacteria (e.g., Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B ) at least 2 weeks prior to therapy initiation 

2.    Member has been vaccinated against encapsulated bacteria less than 2 weeks prior to therapy initiation and will receive prophylactic antibiotics for at least 2 weeks following vaccination 

3.    The member does not have cold agglutinin syndrome secondary to infection, rheumatologic conditions, systemic lupus erythematosus, or hematologic malignancy 

4.    The member will not receive an additional complement inhibitor (eculizumab, ravulizumab, pegcetacoplan) or rituximab

Renewal Approval Criteria 

a)    Continuation of sutimlimab-jome meets the definition of medical necessity for CAD when ALL of the following are met 

a.    Member has a history of beneficial response to sutimlimab-jome therapy–examples of beneficial response include absence of or decreased requirement for red blood cell transfusion compared to baseline, improvement in hemoglobin by 2 g/dL from baseline, hemoglobin greater than or equal to 12 g/dL

b.    Member has been revaccinated against encapsulated bacteria (e.g., Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B) according to current medical guidelines for vaccination while receiving sutimlimab-jome therapy 

c.    The member will not receive an additional complement inhibitor (eculizumab, ravulizumab, pegcetacoplan) or rituximab
 

EXCLUSION CRITERIA

Secondary CAD due to infection, autoimmune disease, lupus, or malignancy.
 
Concurrent therapy with other complement inhibitors or rituximab.

BENEFIT APPLICATION

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

Cold Agglutinin Disease (CAD): Rare autoimmune hemolytic anemia (AIHA) mediated by IgM autoantibodies that activate complement at cold temperatures, leading to hemolysis.
 
Incidence: ~1 per million annually; chronic, debilitating course with transfusion dependence and fatigue.
 
Prior therapies: Historically rituximab, cytotoxic agents, or supportive care; limited efficacy and tolerability.
 
ENJAYMO: First and only targeted therapy approved specifically for CAD.

Regulatory Status

FDA Approval: February 2022; PI revised February 2024.
 
Orphan Drug Designation: Yes (CAD).
 
EMA Approval: Also approved in the EU for CAD.

OTHER CRITERIA

N/A

Rationale

Efficacy: Phase III CARDINAL study: 73% transfusion independence, mean Hb rise ≥2 g/dL.

Safety: Most common AEs include respiratory infections, infusion reactions, and headache. Serious risk = encapsulated bacterial infection → requires vaccination and/or prophylaxis.

Clinical consensus: NCCN and expert panels support sutimlimab for symptomatic CAD with hemolysis and anemia.

Population Reference No. 1 Policy Statement

Supplemental Information

No boxed warning.
 
Monitoring: Hemoglobin, bilirubin, reticulocytes, LDH.
 
Infusion: Administer over ~60 min, with observation.
 
Concomitant therapy: Avoid combined complement inhibitors.

Practice Guidelines and Position Statements

NCCN Hematology Guidelines (2024/2025): Recommends sutimlimab as standard therapy for CAD with hemolysis.
 
International consensus: Supports use in primary CAD with anemia; excludes secondary forms.

References

1. Clinical Pharmacology. Gold Standard, 2023.
 
 
2. DRUGDEX® System. Micromedex, 2023.
 
 
3. ENJAYMO Prescribing Information. Bioverativ USA Inc. Revised 02/2024.
 
 
4. FDA Orphan Drug Designations. 2023.
 
 
5. Berentsen S, et al. Blood 2022;139(9):1194–1206 (CARDINAL trial).

Codes

Applicable Modifiers

N/A

Policy History