Frequently Asked Questions

CAD is a rare type of chronic autoimmune hemolytic anemia with potentially serious consequences.^1-3 In patients with CAD, cold agglutinins (IgM autoantibodies against red blood cell [RBC] antigens) can cause clinical symptoms related to RBC agglutination in cooler parts of the body and ultimately result in hemolytic anemia. Hemolysis in CAD is driven by C1 activation of the classical complement pathway, when cold agglutinins recruit and activate C1, typically at body temperatures under 98 °F (37 °C).^4,5

The most common symptoms of CAD are hemolytic anemia, profound fatigue, and circulatory symptoms.^2,6,7

Chronic hemolysis in CAD leaves patients in constant risk for acute consequences and chronic risks.^1-3,7 Hemolysis in CAD is caused by classical complement pathway-mediated destruction of red blood cells.⁵ Persistent activation of the classical complement pathway can lead to severe anemia due to the destruction of red blood cells.^8-12

CAD is a well-characterized disease that is defined by classical complement-dependent chronic hemolysis and a clonal, low-grade B-cell lymphoproliferative disorder without an underlying condition, whereas CAS is a transient condition, secondary to bacterial or viral infections (ie, Mycoplasma pneumoniae or Epstein-Barr virus), overt malignancies, and autoimmune disorders. Additionally, CAS is usually self-remitting as the associated condition resolves. In contrast, CAD is a chronic condition.^6,13,14

CARDINAL was a phase 3, global, multicenter, open-label, single-arm, 6-month trial to demonstrate the efficacy and safety of ENJAYMO in 24 patients with CAD who received ≥1 transfusion during the preceding 6 months.^14,15*

Composite endpoint: Efficacy was based on the proportion of patients who achieved an Hb level ≥12 g/dL or an increase of ≥2 g/dL from baseline at the treatment assessment time point (TAT) (mean value from Weeks 23, 25, and 26) and both transfusion avoidance and no additional treatment beyond what was permitted per protocol in the trial from Week 5 through Week 26.^14,15

Secondary endpoints assessed: Effect on Hb and laboratory measures of hemolysis (mean change from baseline in bilirubin and LDH) at the TAT.^14†

Long-term safety and durability: Following completion of the 6-month treatment period, patients continued to receive ENJAYMO in a long-term safety and durability of response extension phase for an additional 24 months.^14,15

The CARDINAL study population consisted of patients with a confirmed diagnosis of CAD based on chronic hemolysis, polyspecific direct antiglobulin test (DAT), monospecific DAT specific for C3d, cold agglutinin titer ≥64 at 4 °C, and IgG DAT ≤1+ and a recent blood transfusion in the 6 months prior to enrollment.¹⁵

Patients with CAS secondary to infection, rheumatologic disease, SLE, or overt hematologic malignancy were excluded, whereas patients with a history of or concomitant low-grade lymphoproliferative disease were not excluded. Patients with low-grade lymphoproliferative disease were categorized as patients with bone marrow involvement <10%.¹⁵

No, the label does not restrict or limit the use of ENJAYMO to patients with a history of transfusion. ENJAYMO is indicated to decrease the need for red blood cell (RBC) transfusion due to hemolysis in adults with CAD. ENJAYMO is contraindicated in patients with known hypersensitivity to sutimlimab-jome or any of the inactive ingredients.¹⁶

• The primary endpoint was a composite of Hb improvement, avoidance of transfusions, and avoidance of protocol-prohibited CAD medication^14,15
  • Hemoglobin improvement defined as Hb level ≥12 g/dL at the TAT point OR Hb increase of ≥2 g/dL from baseline at the TAT^†
  • Transfusion avoidance from Week 5 through Week 26
  • No treatment for CAD beyond what was permitted per protocol from Week 5 through Week 26
• The secondary endpoints assessed the effect on Hb and laboratory measures of hemolysis (mean change from baseline in bilirubin and LDH) at the TAT^14,15†

In the CARDINAL trial,^§ a majority of patients (54% [13/24]) met the composite endpoint, which included achieving an Hb increase^15‡:

• 63% (15/24) of patients had an Hb increase^II to ≥12 g/dL or of ≥2 g/dL
• 71% (17/24) of patients maintained transfusion avoidance from Week 5 through Week 26
• 92% (22/24) of patients had no use of additional CAD medication^¶ from Week 5 through Week 26

ENJAYMO provided a rapid and sustained improvement in Hb levels through Week 26^15‡:

• Achieved 2.29 g/dL mean increase in Hb levels at Week 3 (SE: 0.308)
• Achieved 3.18 g/dL mean increase in Hb at TAT (SE: 0.476)

Bilirubin is a key endpoint for CAD because the hemolysis is predominantly extravascular in CAD and takes place in the liver. LDH is mainly a marker of intravascular hemolysis, which is less common in CAD.^5,6,17

ENJAYMO may increase susceptibility to serious infections, including infections caused by encapsulated bacteria such as Neisseria meningitides (any serogroup), Streptococcus pneumoniae, and Haemophilus influenzae.¹⁵

Advise patients of the potential increased risk of infections including infections caused by encapsulated bacteria such as Neisseria meningitides, 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 ENJAYMO. Educate patients on the symptoms of infections and advise them to seek immediate medical attention if any new symptoms of infection occur.¹⁵

There were no meningococcal infections with ENJAYMO seen in the CARDINAL trial.¹⁵

Based on its mechanism of action, ENJAYMO may potentially increase the risk for developing autoimmune diseases such as SLE. Development of SLE has been associated with inherited classical complement deficiency. Patients with SLE or autoimmune disease with positive anti-nuclear antibody were excluded from clinical trials with ENJAYMO. Monitor patients being treated with ENJAYMO for signs and symptoms and manage medically.¹⁵

There were no cases of SLE reported with ENJAYMO in the CARDINAL trial.¹⁵

Patients should be vaccinated against encapsulated bacteria at least 2 weeks prior to initiation of ENJAYMO therapy according to the most current Advisory Committee on Immunization Practices (ACIP) recommendations for patients with persistent complement deficiencies. If urgent ENJAYMO therapy is indicated in an unvaccinated patient, administer vaccine(s) as soon as possible.¹⁵

Patients in CARDINAL were given the following vaccinations if they did not have documentation of vaccination in the 5 years prior to enrollment: Meningococcal conjugate vaccine (MenACWY), Meningococcal type B vaccine (MenB), Streptococcus pneumoniae, and Haemophilus influenzae.¹⁶

Serious adverse reactions were reported in 13% (3/24) of patients who received ENJAYMO. These serious adverse reactions were streptococcal sepsis and staphylococcal wound infection (n=1), arthralgia (n=1), and respiratory tract infection (n=1). None of the adverse reactions led to discontinuation of ENJAYMO in CARDINAL.^{15 §}

The most common adverse reactions occurring in ≥10% of patients were respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheraI edema.¹⁵

No. A REMS program is not required for ENJAYMO.

Patients can receive an infusion 3 ways: in office, at an infusion center, or at home^#

What to know before, during, and after an infusion¹⁵

BEFORE INITIATION

Ensure vaccination status aligns with ACIP recommendations for complement deficiencies. If urgent ENJAYMO therapy is indicated in an unvaccinated patient, administer vaccine(s) as soon as possible.

Immunize at least 2 weeks before first dose of ENJAYMO.

Vaccination reduces, but does not eliminate, infection risk.

DURING INFUSION

Monitor for infusion-related reactions, such as shortness of breath, rapid heartbeat, nausea, flushing, and headache.

Slow or stop the infusion if an infusion reaction occurs and institute appropriate supportive measures.

AFTER INFUSION

Following initial infusion, monitor for 2 hours for signs or symptoms of an infusion and/or hypersensitivity reaction.

For subsequent ENJAYMO infusions, monitor for 1 hour for signs of an infusion reaction.

Patients in CARDINAL were given the following vaccinations if they did not have documentation of vaccination in the 5 years prior to enrollment: Meningococcal conjugate vaccine (MenACWY), Meningococcal type B vaccine, Streptococcus pneumoniae vaccination, and Haemophilus influenzae.

Slow or stop the infusion in case of infusion reaction during ENJAYMO administration. Discontinue ENJAYMO infusion and institute appropriate supportive measures if signs of hypersensitivity reactions, such as cardiovascular instability or respiratory compromise, occur.¹⁵

Patients should be monitored for infusion and/or hypersensitivity reactions following completion of infusion with ENJAYMO¹⁵:

• At least 2 hours following completion of the initial infusion
• One hour following completion of subsequent infusions

If a dose is missed, administer as soon as possible; thereafter, resume dosing every 2 weeks. If the duration after the last dose exceeds 17 days, administer ENJAYMO weekly for 2 weeks, with administration every 2 weeks thereafter.¹⁵

Monitor patients for signs and symptoms of hemolysis if treatment with ENJAYMO is interrupted.¹⁵

ENJAYMO Patient Solutions is here to support your patients from the start and throughout treatment. Patient Support Services may be able to provide eligible patients with education services, reimbursement services, and related materials.

ENJAYMO Financial Assistance Programs may be able to help with the cost of treatment. Access to ENJAYMO at no cost may be available to eligible patients who are uninsured or underinsured. Co-pay assistance may be available for out-of-pocket co-pay or co-insurance costs related to ENJAYMO prescription or infusion costs for eligible patients. Additional terms and conditions apply.**

The ENJAYMO Patient Solutions Co-Pay Program (the “Program”) is not valid for prescriptions covered by or submitted for reimbursement under Medicare, Medicaid, VA, DoD, TRICARE, or similar federal or state programs including any state pharmaceutical assistance programs. The Program is not valid where prohibited by law and savings may vary depending on patients’ out-of-pocket costs. Sanofi reserves the right to modify or terminate the Program at any time without notice. Patients will receive all Program details upon registration.

Please contact ENJAYMO Patient Solutions at 1-833-223-2428, Monday through Friday, 8 am to 8 pm ET, for more information.

Your patients may call ENJAYMO Patient Solutions at 1-833-223-2428, Monday through Friday, 8 am to 8 pm ET, for assistance.

Yes, and you can access the codes here or download the ENJAYMO Billing and Coding Guide for Reimbursement for information regarding coverage and other reimbursement considerations for ENJAYMO.

• STEP 1: Enroll your patients in ENJAYMO Patient Solutions
• STEP 2: Confirm vaccination status and vaccinate as needed
• STEP 3: Determine your patient’s ENJAYMO infusion plan
• STEP 4: Acquire ENJAYMO for your patients^††

Sanofi is committed to helping ensure all patients with CAD have support and access to treatment with ENJAYMO.

• Case Managers and Therapeutic Education Managers are available for your patients and your practice: Case managers are experienced in helping individuals get started on treatment and assisting with insurance-related needs. Patients enrolled in ENJAYMO Patient Solutions will be assigned a case manager to serve as their single point of contact to help them through the onboarding process for ENJAYMO. Therapeutic Education Managers, or TEMs, are available to provide education about ENJAYMO and CAD. TEMs help raise awareness about CAD in the community and educate patients and caregivers. They engage with patients to provide information and facilitate educational events about ENJAYMO and CAD—they are paid to provide educational services on behalf of Sanofi but do not provide medical advice. TEMs will advise patients to talk to their doctor about any healthcare needs
• ENJAYMO Patient Solutions is designed to increase accessibility to treatment while reducing barriers to starting and staying on therapy
• ENJAYMO Co-Pay Assistance Program may be able to help with eligible patients’ treatment costs, such as out-of-pocket, co-payments or co-insurance, and cost of infusion if they meet the program requirements**
• ENJAYMO Patient Assistance Program provides financial support for eligible patients who are uninsured or underinsured

ENJAYMO is available through the following authorized specialty distributors:

At-home infusion is available through CVS Pharmacy. Contact ENJAYMO Patient Solutions at 1-833-233-2428 for more information and to review eligibility requirements.

ENJAYMO, a C1s inhibitor, blocks C1 upstream in the classical complement pathway. ENJAYMO prevents downstream extravascular hemolysis, the predominant form of hemolysis in CAD, as well as preventing downstream intravascular hemolysis. The ENJAYMO mechanism of action allows for the preservation of the important immune surveillance activities of the lectin and alternative pathways.^15,18,19

ENJAYMO is contraindicated in patients with known hypersensitivity to sutimlimab-jome or any of the inactive ingredients.¹⁵