Sutimlimab (Monograph)

Brand name: Enjaymo
Drug class: Complement Inhibitors

Medically reviewed by Drugs.com on Nov 20, 2023. Written by ASHP.

Introduction

Immunoglobulin G (IgG) subclass 4 (IgG4) monoclonal antibody that binds to complement protein component 1, s subcomponent (C1s).

Uses for Sutimlimab

Cold Agglutinin Disease

Used to treat hemolysis in adults with cold agglutinin disease (CAD).

Sutimlimab Dosage and Administration

General

Pretreatment Screening

Vaccinate patients against encapsulated bacteria (e.g., Neisseria meningitides, Streptococcus pneumoniae, Haemophilus influenzae) at least 2 weeks prior to initiation of sutimlimab therapy according to the most current recommendations for patients with persistent complement deficiencies. If urgent sutimlimab therapy is indicated in an unvaccinated patient, vaccinate as soon as possible.

Patient Monitoring

Monitor closely for signs and symptoms of infections.
Monitor for at least 2 hours following completion of the initial infusion for signs or symptoms of an infusion and/or hypersensitivity reaction. Monitor for 1 hour following completion of subsequent infusions for signs or symptoms of an infusion reaction. Interrupt the infusion if a reaction occurs.
Monitor for signs and symptoms of autoimmune disease (e.g., systemic lupus erythematosus) and manage medically.
If treatment with sutimlimab is interrupted, closely monitor for signs and symptoms of recurrent hemolysis (e.g., elevated levels of total bilirubin or lactate dehydrogenase accompanied by a decrease in hemoglobin, or reappearance of symptoms such as fatigue, dyspnea, palpitations, or hemoglobinuria).

Administration

IV Administration

Administer by IV infusion only. May be used as as a diluted or undiluted preparation.

Prior to use, remove the drug from refrigerator and do not shake to minimize foaming.

If using a diluted preparation, withdraw the calculated volume from the appropriate number of vials based on the recommended dosage and dilute the calculated volume with 0.9% sodium chloride injection to a total volume of 500 mL (see Table 1).

If using an undiluted preparation, withdraw the calculated volume from the appropriate number of vials based on the recommended dosage and add to an empty infusion bag (see Table 2).

If the infusion solution is not used immediately, store under refrigeration at 2–8°C. Once removed from refrigeration, allow solution to adjust to room temperature (20–25°C) and administer within 8 hours. Total time from time of preparation, including refrigeration, adjustment to room temperature, and expected infusion time should not exceed 36 hours. In-line infusion warmers may be used, but should not exceed a temperature of 40°C.

Administer infusion only through a 0.2 micron in-line filter with a polyethersulfone (PES) membrane. Prime infusion catheter and/or tubing with the dosing solution immediately before infusion and flush immediately following completion of infusion with a sufficient quantity (approximately 20 mL) of 0.9% sodium chloride injection.

Administer at the rate indicated in Tables 1 and 2. Administer the infusion over 1–2 hours depending on the patient's body weight for the diluted preparation. Administer the undiluted preparation over 1 hour.

Table 1. Infusion Reference Table for Sutimlimab-jome Diluted in 0.9% Sodium Chloride1
Body Weight Range	Dose	Number of Drug Vials Needed	Drug Volume	Volume of NaCl Diluent	Total Volume	Maximum Infusion Rate
39 to <70 kg	6500 mg	6	130 mL	370 mL	500 mL	250 mL/hour
70 to <75 kg	6500 mg	6	130 mL	370 mL	500 mL	500 mL/hour
≥75 kg	7500 mg	7	150 mL	350 mL	500 mL	500 mL/hour

Patients with cardiopulmonary disease may receive the infusion over 120 minutes.

Table 2. Infusion Reference Table for Sutimlimab-jome Undiluted1
Body Weight Range	Dose	Number of Drug Vials Needed	Drug Volume	Maximum Infusion Rate
≥39 to <75 kg	6500 mg	6	130 mL	130 mL/hour
≥75 kg	7500 mg	7	150 mL	150 mL/hour

Patients with cardiopulmonary disease may receive the infusion over 120 minutes.

Dosage

Adults

Cold Agglutinin Disease

IV

Dosage based on body weight. For patients weighing 39 to <75 kg, the recommended dose is 6500 mg. For patients weighing ≥75 kg, the recommended dose is 7500 mg.

Administer by IV infusion weekly for the first 2 weeks, then administer every 2 weeks thereafter. Administer at recommended dosage regimen time points, or within 2 days of these time points.

If a dose is missed, administer as soon as possible; thereafter, resume dosing every 2 weeks. If duration after the last dose exceeds 17 days, administer weekly for 2 weeks, with administration every 2 weeks thereafter.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Cautions for Sutimlimab

Contraindications

Known hypersensitivity to sutimlimab or any of the inactive ingredients.

Warnings/Precautions

Serious Infections

May increase susceptibility to serious infections, including infections caused by encapsulated bacteria such as Neisseria meningitidis (any serogroup), Streptococcus pneumoniae, and Haemophilus influenzae.

Serious infections (bacterial and viral) reported in 15% (10/66) of patients receiving sutimlimab in two phase 3 studies. These infections included sepsis, respiratory, and skin infections; one death reported.

Vaccinate patients for encapsulated bacteria according to most current Advisory Committee on Immunization Practices (ACIP) recommendations for patients with persistent complement deficiencies. Revaccinate in accordance with ACIP recommendations.

Immunize patients without a history of vaccination against encapsulated bacteria at least 2 weeks prior to receiving first dose of sutimlimab. If urgent sutimlimab therapy is indicated in an unvaccinated patient, administer vaccine(s) as soon as possible.

Vaccination reduces, but does not eliminate, the risk of encapsulated bacterial infections.

If administered to patients with active systemic infections, monitor closely for signs and symptoms of worsening infection. Inform patients of signs and symptoms and steps to seek immediate medical care. Consider interruption of sutimlimab in patients undergoing treatment for serious infection. Not studied in patients with chronic systemic infections such as hepatitis B, hepatitis C, or HIV. Consider immune status when initiating treatment.

Infusion-related Reactions

Contraindicated in patients with known hypersensitivity. Administration may result in infusion-related reactions. Infusion-related reactions including shortness of breath, rapid heartbeat, nausea, flushing, headache, hypotension, chest discomfort, pruritus, rash, injection site reaction, and dizziness, reported.

Monitor for infusion-related reactions and interrupt infusion if reaction occurs. Discontinue infusion and institute appropriate supportive measures if signs of hypersensitivity reactions, such as cardiovascular instability or respiratory compromise, occur.

Risk of Autoimmune Disease

Based on mechanism of action, sutimlimab may potentially increase risk for developing autoimmune diseases such as systemic lupus erythematosus (SLE). Development of SLE has been associated with inherited classical complement deficiency. Monitor patients for signs and symptoms and manage medically.

Recurrent Hemolysis After Discontinuation

If treatment is interrupted, closely monitor for signs and symptoms of recurrent hemolysis (e.g., elevated levels of total bilirubin or LDH accompanied by a decrease in hemoglobin, or reappearance of symptoms such as fatigue, dyspnea, palpitations, or hemoglobinuria). Consider restarting sutimlimab-jome if signs and symptoms of hemolysis occur after discontinuation.

Immunogenicity

Potential for immunogenicity. Anti-sutimlimab antibodies reported (duration of exposure up to 177 weeks). No clinically significant effect of anti-drug antibodies on pharmacokinetics, pharmacodynamics, efficacy, or safety of sutimlimab observed.

Specific Populations

Pregnancy

No available data on use in pregnant patients. Human IgG antibodies cross the placental barrier; therefore, sutimlimab may be transmitted from mother to developing fetus. Animal studies in monkeys at doses 2-3 times the maximum recommended human dose did not indicate adverse effects on pregnancy or offspring development. No effects on reproductive and developmental parameters were observed in maternal animals and offspring, respectively.

Lactation

No data on the presence of sutimlimab in human milk, effects on the breastfed child, or effects on milk production. Maternal IgG is known to be present in human milk. Effects of local GI exposure and limited systemic exposure in the breastfed child to sutimlimab are unknown. Consider developmental and health benefits of breastfeeding along with mother's clinical need for sutimlimab and any potential adverse effects on breastfed child from the drug or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness in pediatric patients not established.

Geriatric Use

Of the 66 patients in clinical studies of sutimlimab, 65% were ≥65 years of age including 27% who were ≥75 years of age. No overall differences in safety or effectiveness observed between these and younger patients; however, greater sensitivity of some older individuals cannot be ruled out.

Hepatic Impairment

No pharmacokinetic studies performed in patients with hepatic impairment.

Renal Impairment

No pharmacokinetic studies performed in patients with renal impairment.

Common Adverse Effects

Most common adverse reactions in the CADENZA study (≥18%): rhinitis, headache, hypertension, acrocyanosis, Raynaud's phenomenon. Most common adverse reactions in the CARDINAL study (≥25%): urinary tract infection, respiratory tract infection, bacterial infection, dizziness, fatigue, peripheral edema, arthralgia, cough, hypertension, nausea.

Drug Interactions

No formal drug-drug studies performed.

Sutimlimab Pharmacokinetics

Distribution

Plasma Protein Binding

Binds to complement component 1s in serum.

Elimination

Metabolism

Expected to be metabolized by degradation into small peptides and individual amino acids.

Half-life

21 days at the approved recommended dosage. Terminal elimination half-life and clearance varies at different doses due to target-mediated drug disposition at lower concentrations.

Special Populations

No clinically significant differences in pharmacokinetics observed based on sex, age (19–88 years of age), ethnicity (Japanese, non-Japanese), and mild to moderate renal impairment (30–89 mL/minute per 1.73 m²).

Effects of severe renal impairment and hepatic impairment on pharmacokinetics unknown.

Exposures decreased up to 59% for a patient weighing 98 kg and increased up to 57% for a patient weighing 50.5 kg as compared with a patient weighing 72 kg.

Stability

Storage

Parenteral

Concentrate, for injection, for IV infusion

Vials: store at 2–8°C in original carton; protect from light. Do not freeze or shake. Discard unused portion.

Infusion solution: store at 2–8°C if not used immediately.

Actions

Humanized IgG4 monoclonal antibody.
Inhibition of the classical complement pathway at the level of C1s prevents deposition of complement opsonins on the surface of RBCs, resulting in inhibition of hemolysis in patients with cold agglutinin disease.
Does not inhibit the lectin and alternative pathways.

Advice to Patients

Advise patients of the potential increased risk of infections including infections caused by encapsulated bacteria such as Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. These infections may be serious or life-threatening. Inform patients that they are required to receive vaccinations against these bacteria according to current medical guidelines prior to initiation of and during treatment with sutimlimab. Educate patients on the symptoms of infections and advise them to seek immediate medical attention if any new symptoms of infection occur.
Advise patients that administration of sutimlimab may result in infusion-related reactions including hypersensitivity reactions. Hypersensitivity reactions may be serious or life-threatening (e.g., anaphylaxis). Educate patients on the symptoms of infusion-related reactions and advise them to seek medical attention if any new symptoms of infusion-related reactions occur.
Educate patients that there may be an increased risk of developing an autoimmune disease such as systemic lupus erythematosus (SLE) during sutimlimab therapy. Advise patients on signs and symptoms of SLE and to report any new symptoms of SLE and seek medical attention.
Inform patients that they may develop hemolysis due to cold agglutinin disease when sutimlimab is discontinued and that they should be monitored by their healthcare provider following sutimlimab discontinuation.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise women to inform clinicians if they are of plan to become pregnant or plan to breast-feed.
Advise patients of other important precautionary information.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Sutimlimab is obtained through specialty pharmacy distributors. Contact the manufacturer or consult the Enjaymo website ([Web]) for specific availability information.