Adverse reactions : תופעות לוואי

4.8     Undesirable effects

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 open- label 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 
MedDRA System Organ Class                 Very common                                 Common Infections and infestations               Urinary tract infection                     Lower respiratory tract Cystitis                                    infectionsc
Upper respiratory tract                     Urosepsis infectionsa                                 Escherichia urinary tract Nasopharyngitisb                            infection
Gastroenteritis                             Urinary tract infection bacterial Rhinitis                                    Cystitis bacterial
Oral herpes
Herpes simplex viraemia
Herpes zoster
Herpes simplex

General disorders and                                                                 Pyrexiaf administration site conditions                                                        Feeling coldf Infusion related reactionsf

Nervous system disorders                  Headache                                    Auraf Dizzinessf*

Vascular disorders                        Hypertensiond                               Hypotensionf* Cyanosis (reported as                       Stress cardiomyopathyf acrocyanosis)
Raynaud’s phenomenon
Gastrointestinal disorders                Abdominal paine                             Diarrhoeaf Nausea                                      Dyspepsiaf
Aphthous ulcerf

Respiratory, thoracic and                                                             Chest discomfortf* mediastinal disorders
Skin and subcutaneous tissue                                                          Pruritusf* disorders
 aUpper   respiratory tract infections: upper respiratory tract infection, bronchitis, and viral upper respiratory tract infection bNasopharyngitis:    nasopharyngitis, pharyngitis c Lower respiratory tract infections: pneumonia klebsiella, COVID-19 pneumonia, lower respiratory tract infection,  respiratory tract infection viral, respiratory tract infection, pneumonia dHypertension: hypertension, blood pressure increased, essential hypertension, hypertensive crisis, white coat hypertension eAbdominal pain: abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness fInfusion 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 authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse event should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il/