ENJAYMO Solution for infusion Ref.[50928] Active ingredients: Sutimlimab

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Infections

Enjaymo targets the classical complement pathway (CP) specifically binding to complement protein component 1, s subcomponent (C1s) preventing the cleavage of complement protein C4. Although the lectin and alternate pathways remain unaffected, patients may have an increased susceptibility to serious infections, especially infections caused by encapsulated bacteria such as Neisseria meningitides, Streptococcus pneumoniae, and Haemophilus influenza. Patients should be vaccinated against encapsulated bacteria before treatment with Enjaymo is started, please see “Vaccinations” below.

In clinical studies with CAD, serious infections, including sepsis, have been reported in patients receiving treatment with Enjaymo (see section 4.8). Enjaymo should not be initiated in patients with active, serious infections. Patients should be monitored for early signs and symptoms of infections and should be informed to seek immediate medical care if such symptoms should occur.

Patients with viral hepatitis and HIV were excluded from the clinical studies. Before and during treatment, patients must notify their physician if they have been diagnosed with hepatitis B, hepatitis C, or HIV infection. Be cautious when treating patients with a history of hepatitis B, hepatitis C, or HIV infection.

Vaccinations

Vaccinate patients according to the most current local recommendations for patients with persistent complement deficiencies, including meningococcal and streptococcal vaccines. Revaccinate patients in accordance with local recommendations.

Immunize patients without a history of vaccination against encapsulated bacteria at least 2 weeks prior to receiving the first dose of Enjaymo. If urgent Enjaymo therapy is indicated in an unvaccinated patient, administer vaccine(s) as soon as possible. The benefits and risks of antibiotic prophylaxis for prevention of infections in patients receiving Enjaymo have not been established.

Hypersensitivity reactions

As with other protein products, administration of Enjaymo may result in hypersensitivity reactions, including anaphylaxis. In clinical studies, no serious hypersensitivity reactions were observed with Enjaymo. If hypersensitivity reactions occur, discontinue Enjaymo and initiate appropriate treatment.

Infusion-related reactions

Administration of Enjaymo may result in infusion-related reactions during the infusion or immediately after the infusion (see section 4.8). Patients should be monitored for infusion-related reactions, infusion interrupted if a reaction occurs and appropriate treatment initiated.

Systemic lupus erythematosus (SLE)

Individuals with inherited classical complement deficiency are at a higher risk for developing SLE. Patients with SLE were excluded from clinical studies with Enjaymo. Patients being treated with Enjaymo should be monitored for signs and symptoms of SLE and evaluated appropriately. Use Enjaymo with caution in patients with SLE or those who develop signs and symptoms of SLE.

Monitoring CAD manifestations after Enjaymo discontinuation

The effects on haemolysis diminish after end of treatment. Patients should therefore be monitored for signs and symptoms of haemolysis in case of treatment discontinuation.

Sodium

This medicinal product contains 3.5 mg per mL or 77 mg sodium per vial, equivalent to 3.85% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

No interaction studies have been performed. Enjaymo is an unlikely candidate for cytochrome P450 mediated drug-drug interactions as it is a recombinant human protein. The interaction of sutimlimab with substrates of CYPs has not been studied. However, sutimlimab decreases the levels of proinflammatory cytokines in patients, such as IL-6 which is known to supress the expression of specific hepatic CYP450 enzymes (CYP1A2, CYP2C9, CYP2C19, and CYP3A4). Therefore, caution should be exercised when starting or discontinuing sutimlimab treatment in patients also receiving substrates of CYP450 3A4, 1A2, 2C9 or 2C19, particularly those with a narrow therapeutic index (such as warfarin, carbamazepine, phenytoin and theophylline), and doses adjusted if needed.

Pregnancy

There are no available data on sutimlimab from the use in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Human IgG antibodies are known to cross the placental barrier; therefore, sutimlimab may be transmitted from the mother to the developing foetus.

As a precautionary measure, it is preferable to avoid the use of sutimlimab during pregnancy. Sutimlimab should be given during pregnancy only if clearly indicated.

Breast-feeding

Human IgGs are known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. It is unknown whether sutimlimab/metabolites are excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from sutimlimab therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

Effects of sutimlimab on male and female fertility have not been studied in animals. In repeat-dose studies with sutimlimab with exposures at up to approximately 4 times the recommended human dose, no effects on reproductive organs were observed in cynomolgus monkeys.

Enjaymo has no or negligible influence on the ability to drive and use machines.

Summary of safety profile

The most frequently reported adverse reactions with Enjaymo in CADENZA and CARDINAL clinical studies were headache, hypertension, urinary tract infection, upper respiratory tract infection, nasopharyngitis, nausea, abdominal pain, infusion-related reactions and cyanosis (reported as acrocyanosis).

Tabulated list of adverse reactions

The safety evaluation of Enjaymo in patients with CAD was primarily based on data from 66 patients who participated in the phase 3, randomized, placebo-controlled study (CADENZA) and in an openlabel single-arm study (CARDINAL).

Listed in Table 2 are adverse reactions observed in the CADENZA and CARDINAL studies presented by system organ class and frequency, using the following categories: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 2. List of adverse reactions in CADENZA and CARDINAL studies:

^a Upper respiratory tract infections: upper respiratory tract infection, bronchitis, and viral upper respiratory tract infection
^b Nasopharyngitis: nasopharyngitis, pharyngitis
^c Lower respiratory tract infections: pneumonia klebsiella, COVID-19 pneumonia, lower respiratory tract infection, respiratory tract infection viral, respiratory tract infection, pneumonia
^d Hypertension: hypertension, blood pressure increased, essential hypertension, hypertensive crisis, white coat hypertension
^e Abdominal pain: abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness
^f Infusion related reaction: All occurred within 24 hours of start of Enjaymo infusion.
^* Events suggestive of hypersensitivity reactions are included in the table.

Serious infections

Of the 66 patients who participated in CADENZA and CARDINAL studies, serious infections were reported in 10 (15.2%) patients. Serious infections listed in the ADR table include respiratory tract infection [pneumonia klebsiella (n=1), respiratory tract infection (n=1), COVID-19 pneumonia (n=1)], urinary tract infection [urosepsis (n=1), urinary tract infection (n=1), urinary tract infection bacterial (n=1)], herpes zoster (n=1). Sutimlimab was discontinued in one patient due to a serious infection of Klebsiella pneumonia with fatal outcome. No other fatal events of infections were reported. See section 4.4 for information on vaccination recommendations for serious infections and for monitoring early signs and symptoms of infections.

Immunogenicity

Immunogenicity of sutimlimab was assessed in CAD patients in the CARDINAL and CADENZA studies at baseline, during the treatment period, and at end of treatment (Week 26). Two of the 24 patients (8.3%) enrolled in the CARDINAL study who received at least one dose of sutimlimab developed treatment-emergent ADAs. In CADENZA, 6 of 42 patients treated with sutimlimab (14.3%) developed treatment-emergent ADAs. These ADAs were transient in nature with low titre and were not associated with changes in the pharmacokinetic profile, clinical response, or adverse events.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.