Enjaymo (Sutimlimab)
Monoclonal antibody for cold agglutinin disease (CAD)
Quick Facts About Enjaymo
Key Takeaways About Enjaymo
- First targeted therapy for CAD: Enjaymo is the first approved treatment specifically targeting the classical complement pathway in cold agglutinin disease
- Reduces hemolysis rapidly: Clinical trials showed significant improvement in hemoglobin levels and reduction in blood transfusion needs within weeks of starting treatment
- Vaccination required before starting: Meningococcal and streptococcal vaccines must be given at least 2 weeks before the first infusion due to increased infection risk
- Regular infusions needed: After two loading doses (Day 0 and Day 7), maintenance infusions are given every 2 weeks at a healthcare facility or at home
- Monitor for infections: Because Enjaymo inhibits part of the immune system, patients should be vigilant for signs of serious infections, particularly meningococcal and streptococcal infections
What Is Enjaymo and What Is It Used For?
Enjaymo (sutimlimab) is a monoclonal antibody that treats hemolytic anemia in adults with cold agglutinin disease (CAD). It works by selectively blocking the C1s protein in the classical complement pathway, preventing the immune system from destroying red blood cells. This reduces anemia and the associated fatigue.
Cold agglutinin disease is a rare autoimmune hemolytic anemia in which certain antibodies in the immune system bind to red blood cells, particularly at lower temperatures. This binding activates the classical complement pathway – a cascade of immune proteins – which leads to the premature destruction of red blood cells, a process known as hemolysis. The resulting shortage of red blood cells causes anemia, leading to persistent fatigue, weakness, shortness of breath, and in some cases, circulatory problems such as Raynaud's phenomenon or acrocyanosis.
Enjaymo contains the active substance sutimlimab, a humanized immunoglobulin G4 (IgG4) monoclonal antibody. It specifically targets and inhibits complement protein C1s, the serine protease that initiates the classical complement cascade. By blocking C1s, sutimlimab prevents the downstream activation of complement components C2, C3, and C4, effectively halting the complement-mediated destruction of red blood cells. Importantly, sutimlimab does not affect the lectin or alternative complement pathways, preserving significant aspects of immune defense.
In clinical trials, including the pivotal CARDINAL study, Enjaymo demonstrated rapid and sustained improvements in hemoglobin levels. Many patients achieved normalization of hemoglobin and bilirubin levels, and the need for blood transfusions was significantly reduced. Patients also reported meaningful improvements in fatigue and overall quality of life. Enjaymo was approved by the U.S. FDA in February 2022 and by the European Medicines Agency (EMA) in December 2022, making it the first treatment specifically developed and approved for cold agglutinin disease.
CAD is estimated to affect approximately 5–20 per million people. It primarily occurs in adults over 60 years of age and is more common in women. CAD can be primary (idiopathic) or secondary to other conditions such as lymphoproliferative disorders or infections. Before Enjaymo, treatment options were limited to supportive care (blood transfusions, cold avoidance) and off-label use of rituximab-based therapies.
How does Enjaymo differ from other treatments?
Unlike rituximab-based therapies that target B cells producing the pathogenic cold agglutinin antibodies, Enjaymo works downstream by directly blocking the complement cascade. This means the onset of action is much faster – hemolysis can be controlled within days rather than the weeks or months needed for B-cell depletion to take effect. Furthermore, Enjaymo does not cause B-cell depletion, potentially preserving the patient's adaptive immune function for fighting infections.
Compared to supportive measures like blood transfusions and cold avoidance, Enjaymo addresses the underlying pathophysiology of CAD rather than merely managing symptoms. This targeted approach has been shown to provide more consistent and sustained control of hemolysis and anemia.
What Should You Know Before Taking Enjaymo?
Before starting Enjaymo, you must receive meningococcal and streptococcal vaccinations at least 2 weeks in advance. Tell your doctor about any current infections, history of hepatitis B or C, HIV, autoimmune conditions (particularly lupus), or if you are pregnant or breastfeeding. Enjaymo should not be used if you are allergic to sutimlimab or any of its ingredients.
Contraindications
Enjaymo must not be given if you have a known allergy (hypersensitivity) to sutimlimab or to any of the other ingredients in the formulation, which include polysorbate 80, sodium chloride, dibasic sodium phosphate, monobasic sodium phosphate, and water for injections. Signs of an allergic reaction may include difficulty breathing or swallowing, swelling of the face, lips, tongue, or throat, severe itching with rash, or dizziness. If you experience any of these symptoms during or after an infusion, seek medical attention immediately.
Warnings and Precautions
Because Enjaymo inhibits a part of the complement system, patients have an increased susceptibility to infections, particularly those caused by encapsulated bacteria such as Neisseria meningitidis (meningococcal disease) and Streptococcus pneumoniae (pneumococcal disease). Your doctor will ensure you receive appropriate vaccinations before starting therapy.
It is recommended that you are vaccinated at least 2 weeks before the first dose of Enjaymo. However, vaccination does not guarantee complete protection. You should remain vigilant for any signs of infection throughout your treatment. Contact your doctor immediately if you develop symptoms such as fever with or without rash, chills, flu-like symptoms, cough, difficulty breathing, headache with nausea or vomiting, stiff neck, confusion, sensitivity to light, or painful or frequent urination.
Enjaymo blocks part of the complement immune system, increasing the risk of life-threatening meningococcal and other serious bacterial infections. Seek emergency medical care immediately if you develop sudden high fever, severe headache with stiff neck, a spreading rash of dark purple spots, or confusion. These could be signs of meningococcal infection, which can progress rapidly and be fatal if not treated promptly.
Infusion-related reactions: Some patients may experience reactions during or shortly after the infusion. Symptoms can include nausea, flushing, headache, difficulty breathing, and rapid heartbeat. Your healthcare team will monitor you during and after each infusion – for at least 2 hours after the first infusion and at least 1 hour after subsequent infusions. If a reaction occurs, the infusion may be slowed or stopped.
Systemic lupus erythematosus (SLE): Tell your doctor if you have an autoimmune condition such as systemic lupus erythematosus. Seek medical attention if you develop symptoms of SLE, including joint pain or swelling, a rash on the cheeks and nose (butterfly rash), or unexplained fever.
Pregnancy and Breastfeeding
The effects of Enjaymo during pregnancy have not been established. Animal studies are insufficient to determine potential harm to the developing fetus. If you are pregnant, think you may be pregnant, or are planning to have a baby, discuss the risks and benefits with your doctor before receiving treatment. Enjaymo should only be used during pregnancy if clearly recommended by your physician.
It is not known whether sutimlimab passes into breast milk. Because monoclonal antibodies can be secreted in breast milk, there is a potential risk to the nursing infant. You and your healthcare provider should decide together whether to breastfeed or to receive Enjaymo, considering the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Children and Adolescents
Enjaymo is not intended for use in children and adolescents under 18 years of age, as cold agglutinin disease does not typically occur in this age group. Safety and efficacy data in pediatric patients have not been established.
Driving and Operating Machinery
Enjaymo has no or negligible effect on the ability to drive and use machines. No impairment has been observed in clinical studies.
Each vial of Enjaymo contains 77 mg of sodium (approximately 3.85% of the WHO recommended maximum daily intake for adults). This should be taken into consideration if you are on a sodium-restricted diet.
How Does Enjaymo Interact with Other Drugs?
No formal drug interaction studies have been conducted with Enjaymo. Tell your doctor about all medications you are currently taking, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements. Because Enjaymo suppresses part of the complement system, caution is advised when combining it with other immunosuppressive therapies.
Sutimlimab is a monoclonal antibody that is cleared through intracellular catabolism (protein degradation) rather than through hepatic metabolism by cytochrome P450 enzymes. Therefore, traditional pharmacokinetic drug-drug interactions mediated by CYP enzymes are not expected. However, the clinical implications of combining Enjaymo with other immunomodulatory or immunosuppressive agents have not been fully characterized.
Because Enjaymo inhibits the classical complement pathway, concurrent use with other complement inhibitors or immunosuppressants may further increase susceptibility to infections. If you are receiving or planning to receive other treatments that affect the immune system, your healthcare provider should carefully weigh the potential benefits against the increased infection risk.
| Drug Category | Examples | Concern | Recommendation |
|---|---|---|---|
| Other complement inhibitors | Eculizumab, ravulizumab | Additive complement suppression; greatly increased infection risk | Generally avoid combination; consult specialist |
| Immunosuppressants | Rituximab, corticosteroids, azathioprine | Increased risk of serious infections due to combined immune suppression | Use with caution; close monitoring |
| Live vaccines | MMR, varicella, yellow fever | Potential for reduced vaccine efficacy or increased risk from live organisms | Complete live vaccinations before starting Enjaymo if possible |
| Anticoagulants | Warfarin, heparin | No known direct interaction, but monitor for bleeding events | Standard monitoring; no dose adjustment expected |
It is important to inform your doctor about all medications you are taking before each infusion. This includes prescription drugs, non-prescription medicines, dietary supplements, and herbal products. Your doctor will determine whether any adjustments to your treatment plan are necessary.
What Is the Correct Dosage of Enjaymo?
Enjaymo is dosed based on body weight: 6,500 mg for patients weighing 39 to less than 75 kg, or 7,500 mg for patients weighing 75 kg or more. Treatment starts with two loading doses (Day 0 and Day 7), followed by maintenance infusions every 2 weeks. Each infusion takes 1–2 hours and is given by a healthcare professional.
Enjaymo is administered exclusively by healthcare professionals as an intravenous infusion. The dose is determined by your body weight, and the same dose is used for both the loading phase and the maintenance phase. No dose adjustments are required for age, renal function, or hepatic function based on available data.
Adults
| Body Weight | Dose | Vials Required | Infusion Volume | Max Infusion Rate |
|---|---|---|---|---|
| 39 kg to <75 kg | 6,500 mg | 6 vials | 130 mL | 130 mL/h |
| ≥75 kg | 7,500 mg | 7 vials | 150 mL | 150 mL/h |
Treatment Schedule
- Day 0: First loading dose
- Day 7: Second loading dose (1 week later)
- Every 2 weeks thereafter: Maintenance infusions
Each infusion is administered over 1–2 hours depending on body weight, through a 0.22 micrometer polyethersulfone membrane inline filter.
Children
Enjaymo is not approved for use in patients under 18 years of age. Cold agglutinin disease is extremely rare in children and adolescents, and no pediatric clinical data are available.
Elderly
No dose adjustment is necessary for elderly patients. CAD predominantly affects older adults, and the clinical trial population included patients up to 85 years of age. Efficacy and safety profiles were consistent across age groups in the CARDINAL study.
Missed Dose
If you miss a scheduled infusion appointment, contact your doctor as soon as possible to reschedule. It is important to maintain the regular dosing schedule to ensure consistent control of hemolysis. Delaying or missing doses may lead to a recurrence of symptoms as complement-mediated hemolysis resumes.
Overdose
Because Enjaymo is administered by healthcare professionals in a clinical setting, overdose is unlikely. No cases of overdose have been reported in clinical trials. If you believe you have received more than the prescribed dose, contact your doctor. Treatment would be supportive, as there is no specific antidote for sutimlimab.
Home Infusion
After receiving Enjaymo at a healthcare facility for at least three months without complications, your doctor may consider allowing home infusions. Home infusions are always administered by a qualified healthcare professional who remains present throughout the infusion and for at least one hour afterward. Your doctor will assess your suitability for home infusions based on your medical stability, absence of infusion-related reactions, and ability to follow the required procedures. If you experience side effects during a home infusion, the infusion will be stopped immediately and your doctor will determine whether future infusions should be given at a clinical facility.
When treatment is discontinued, the protective effects will gradually diminish. Your doctor will monitor you closely for the return of CAD symptoms, which may include fatigue, shortness of breath, rapid heartbeat, or dark-colored urine caused by the renewed destruction of red blood cells. Do not stop treatment without discussing it with your healthcare provider.
What Are the Side Effects of Enjaymo?
The most common side effects of Enjaymo include infections (respiratory, urinary, gastrointestinal), headache, high blood pressure, Raynaud's phenomenon, abdominal pain, and nausea. Serious but less common side effects include severe infections, infusion-related reactions, and allergic reactions. Contact your doctor immediately if you develop signs of infection or an allergic reaction.
Like all medicines, Enjaymo can cause side effects, although not everyone will experience them. The side effects observed in clinical trials are categorized below by how frequently they occur. It is important to report any unusual symptoms to your healthcare team, as early identification and management of side effects can improve your treatment experience.
Very Common
- Infections: upper respiratory tract, urinary tract, gastrointestinal (stomach and intestines), common cold, runny nose
- Headache
- High blood pressure (hypertension)
- Raynaud's phenomenon / acrocyanosis (poor circulation with skin discoloration in hands and feet in response to cold or stress)
- Abdominal pain
- Nausea
Common
- Infections: lower respiratory tract, urinary tract (more severe), herpes virus infections
- Infusion-related reactions (nausea, flushing, headache, difficulty breathing, rapid heartbeat)
- Fever (pyrexia)
- Chills (feeling cold)
- Dizziness
- Aura (visual disturbances)
- Low blood pressure (hypotension)
- Diarrhea
- Stomach discomfort (dyspepsia)
- Mouth ulcers (aphthous stomatitis)
- Chest discomfort
- Itching (pruritus)
- Signs of allergic reaction: Difficulty breathing or swallowing, swelling of face, lips, tongue, or throat, severe itching with rash, feeling dizzy or faint
- Signs of serious infection: Fever with or without rash, chills, flu-like symptoms, severe headache with stiff neck, confusion, light sensitivity, painful or frequent urination
- Signs of infusion reaction: Nausea, flushing, headache, breathing difficulty, rapid heartbeat during or shortly after infusion
If any of these symptoms occur during an infusion, the infusion should be stopped immediately. Contact your healthcare team without delay.
Long-term Safety Considerations
Because Enjaymo inhibits a part of the complement immune system on an ongoing basis, long-term use carries a continued increased risk of infections, particularly from encapsulated bacteria. Your doctor will monitor your health regularly and may recommend booster vaccinations. The long-term safety profile continues to be studied through post-marketing surveillance and ongoing clinical trials.
Patients receiving Enjaymo should carry a patient alert card at all times, detailing their increased risk of meningococcal and other infections. This ensures that any healthcare provider treating you in an emergency is aware of your medication and can take appropriate precautions.
Reporting Side Effects
Reporting suspected side effects after a medicine has been authorized is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients are encouraged to report side effects to their national pharmacovigilance authority, such as the MHRA (UK), FDA MedWatch (US), or EMA EudraVigilance (EU).
How Should You Store Enjaymo?
Store Enjaymo refrigerated at 2°C–8°C (36°F–46°F). Do not freeze. Keep in the original packaging to protect from light. After preparation, use immediately. Enjaymo is typically stored and prepared by healthcare professionals at the treatment facility.
Enjaymo is a biological medicine that requires careful storage to maintain its efficacy and safety. As a hospital- or clinic-administered medication, storage is primarily the responsibility of healthcare professionals, but understanding proper handling is important for patient awareness.
Unopened Vials
- Store in a refrigerator at 2°C to 8°C (36°F to 46°F)
- Do not freeze. If accidentally frozen, do not use the product
- Keep vials in the original carton to protect from light
- Do not use after the expiration date printed on the label and carton (the last day of the stated month)
After Opening / Preparation
Once prepared, the infusion solution should be used immediately. Chemical and physical stability after opening has been demonstrated for up to 16 hours at 18°C–25°C (room temperature) or 72 hours at 2°C–8°C (refrigerated). From a microbiological perspective, the prepared solution should be used as soon as possible. If not used immediately, storage should typically not exceed 24 hours at 2°C–8°C or 8 hours at room temperature, provided preparation was performed under controlled aseptic conditions.
Keep all medicines out of the sight and reach of children. Do not dispose of Enjaymo via household waste or wastewater. Your healthcare team will ensure proper disposal of unused medicine to protect the environment.
What Does Enjaymo Contain?
Each 22 mL vial of Enjaymo contains 1,100 mg of sutimlimab (50 mg/mL). Inactive ingredients include polysorbate 80, sodium chloride, dibasic sodium phosphate, monobasic sodium phosphate, and water for injections. The solution is opalescent, colorless to slightly yellow, and essentially free of visible particles.
Active Ingredient
The active substance is sutimlimab. Each single-use vial contains 22 mL of solution at a concentration of 50 mg/mL, providing 1,100 mg of sutimlimab per vial. Sutimlimab is a humanized IgG4 monoclonal antibody produced in Chinese hamster ovary (CHO) cells using recombinant DNA technology.
Inactive Ingredients (Excipients)
- Polysorbate 80 (E 433): A surfactant that helps stabilize the protein in solution and prevents aggregation
- Sodium chloride: Maintains the osmolality and tonicity of the solution
- Dibasic sodium phosphate (E 339): Acts as a buffer to maintain pH stability
- Monobasic sodium phosphate (E 339): Acts as a buffer to maintain pH stability
- Water for injections: The solvent base for the formulation
Each vial contains 77 mg of sodium, corresponding to approximately 3.85% of the WHO recommended maximum daily intake for adults. The solution appears opalescent and colorless to slightly yellow. Do not use the solution if it appears discolored or contains foreign particles. Enjaymo is available in packs containing 1 or 6 vials, although not all pack sizes may be marketed in every country.
Frequently Asked Questions About Enjaymo
Cold agglutinin disease (CAD) is a rare type of autoimmune hemolytic anemia. In CAD, the immune system produces antibodies (cold agglutinins) that bind to red blood cells at low temperatures. This triggers the classical complement pathway, leading to the destruction (hemolysis) of red blood cells. Symptoms include chronic anemia with fatigue, weakness, shortness of breath, and circulatory problems such as Raynaud's phenomenon. CAD predominantly affects older adults and is estimated to affect 5–20 per million people.
Enjaymo acts rapidly on the complement system. In clinical trials, significant inhibition of complement-mediated hemolysis was observed within days of the first infusion. Many patients showed measurable improvements in hemoglobin levels and markers of hemolysis (such as bilirubin) within the first 1–3 weeks. However, the full clinical benefit, including normalization of hemoglobin and reduction in fatigue, typically develops over several weeks of continued treatment.
Yes, home infusion may be an option after you have received Enjaymo at a healthcare facility for at least three months without experiencing infusion-related reactions. Your doctor will evaluate whether you are a suitable candidate based on your medical stability, absence of complications, and your ability to follow the home infusion procedures. A qualified healthcare professional will administer the infusion at home and remain present throughout and for at least one hour afterward.
Enjaymo is not a cure for CAD. It controls the disease by blocking complement-mediated hemolysis, but it does not eliminate the underlying cold agglutinin antibodies. If treatment is stopped, the complement pathway becomes active again and hemolysis will resume. Therefore, Enjaymo is considered a long-term maintenance therapy that needs to be continued to maintain its protective effect.
Contact your doctor promptly if you develop any signs of infection, such as fever, chills, cough, sore throat, body aches, or urinary symptoms. Because Enjaymo suppresses part of the immune system, infections can be more serious. In particular, be alert for signs of meningococcal infection – sudden high fever, severe headache, stiff neck, and a spreading dark purple rash – which requires emergency medical care. Your doctor may temporarily adjust your treatment plan if you have a serious active infection.
All information is based on the European Medicines Agency (EMA) approved Summary of Product Characteristics (SmPC) for Enjaymo, FDA prescribing information, the CARDINAL clinical trial (Phase 3), peer-reviewed publications in the New England Journal of Medicine and Blood, and international hematology guidelines. All medical claims reflect evidence from controlled clinical trials and post-marketing data reviewed by regulatory authorities.
References
- European Medicines Agency (EMA). Enjaymo (sutimlimab) – Summary of Product Characteristics. Last updated 2025. Available at: EMA EPAR – Enjaymo
- U.S. Food and Drug Administration (FDA). ENJAYMO Prescribing Information. Approved February 2022. Available at: FDA.gov
- Roth A, Berentsen S, Enghard P, et al. Sutimlimab in cold agglutinin disease. New England Journal of Medicine. 2021;384(14):1323-1334. doi:10.1056/NEJMoa2027760
- Roth A, et al. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA study. Blood. 2022;140(9):980-991.
- Berentsen S, Barcellini W. Autoimmune hemolytic anemias. New England Journal of Medicine. 2024;391:1530-1543.
- Berentsen S. How I manage patients with cold agglutinin disease. British Journal of Haematology. 2021;193(4):688-700.
- World Health Organization (WHO). Model List of Essential Medicines – 23rd edition, 2023.
- Jager U, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Reviews. 2020;41:100648.
Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, composed of licensed physicians specializing in hematology, immunology, and clinical pharmacology.
All content is reviewed according to international medical guidelines from the EMA, FDA, and WHO. We follow the GRADE evidence framework and maintain editorial independence from pharmaceutical companies.
Information is based on peer-reviewed clinical trials, regulatory agency assessments (EMA EPAR, FDA prescribing information), and established clinical guidelines. Evidence level: 1A where applicable.
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