Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The most commonly reported adverse reactions in patients treated with ASPAVELI were injection site reactions: injection site erythema, injection site pruritus, injection site swelling, injection site pain, injection site bruising. Other adverse reactions reported in more than 10% of patients during clinical studies were upper respiratory tract infection, diarrhoea, haemolysis, abdominal pain, headache, fatigue, and pyrexia, cough, urinary tract infection, vaccination complication, dizziness, pain in extremity, arthralgia, back pain, nausea. The most commonly reported serious adverse reactions were haemolysis and sepsis.

Tabulated list of adverse reactions
Table 1 gives the adverse reactions observed from the clinical studies and postmarketing experience with pegcetacoplan in patients with PNH. Adverse reactions are listed by MedDRA system organ class (SOC) and frequency, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100) or rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), and not known (cannot be estimated from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.


Table 1: Adverse reactions from clinical trials1 and postmarketing experience MedDRA System Organ Class                 Frequency         Adverse reaction Infections and infestations               Very common       Upper respiratory tract infection Urinary tract infection
Common            Sepsis
Gastrointestinal infection
Fungal infection
Skin infection
Oral infection
Ear infection
Infection
Respiratory tract infection
Viral infection
Bacterial infection
Hordeolum
Uncommon          COVID-19
Cervicitis
Groin infection
Pneumonia
Nasal abscess
Ophthalmic herpes zoster
Vulvovaginal mycotic infection
Blood and lymphatic system disorders      Very common       Haemolysis Common            Thrombocytopenia
Neutropenia
Metabolism and nutrition disorders        Common            Hypokalaemia Psychiatric disorders                     Common            Anxiety
Nervous system disorders                  Very common       Headache
Dizziness
Vascular disorders                        Common            Hypertension Respiratory, thoracic and mediastinal     Very common        Cough disorders                                 Common             Dyspnoea Epistaxis
Oropharyngeal pain
Nasal congestion
Gastrointestinal disorders                Very common        Abdominal pain Diarrhoea
Nausea
Skin and subcutaneous tissue disorders    Common             Erythema Rash
Uncommon           Urticaria2
Musculoskeletal and connective tissue     Very common        Arthralgia disorders                                                    Back pain Pain in extremity
Common             Myalgia
Muscle spasms
Renal and urinary disorders               Common             Acute kidney injury Chromaturia
General disorders and administration site Very common        Injection site erythema conditions                                                   Injection site pruritus Injection site swelling
Injection site bruising
Fatigue
Pyrexia
Injection site pain

MedDRA System Organ Class                    Frequency             Adverse reaction Common                Injection site reaction
Injection site induration
Investigations                               Common                Alanine aminotransferase increased Bilirubin increased
Injury, poisoning and procedural             Very common           Vaccination complication3 complications
1
Studies APL2-302, APL2-202, APL2-CP-PNH-204, and APL-CP0514 in PNH patients.
Medically similar terms are grouped, where appropriate, on the basis of similar medical concept.
2
Estimated from postmarketing experience.
3
Vaccination complications were related to the mandatory vaccinations.

Description of selected adverse reactions
Infections
Based on its mechanism of action, the use of pegcetacoplan may potentially increase the risk of infections, particularly infections caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae (see section 4.4). No serious infection caused by encapsulated bacteria was reported during Study APL2-302. Forty-eight patients experienced an infection during the study. The most frequent infections in patients treated with pegcetacoplan during Study APL2-302 were upper respiratory tract infection (28 cases, 35%). Most infections reported in patients treated with pegcetacoplan during study APL2-302 were non-serious, and predominantly mild in intensity. Ten patients developed infections reported as serious including one patient who died due to COVID-19. The most frequent serious infections were sepsis (3 cases) (leading to discontinuation of pegcetacoplan in one patient) and gastroenteritis (3 cases); all of which resolved.

Haemolysis
Nineteen patients reported haemolysis during Study APL2-302 in patients treated with pegcetacoplan.
Seven cases were reported as serious, and 5 cases led to discontinuation of pegcetacoplan and the dose of pegcetacoplan was increased in 10 patients.

Immunogenicity
Anti-drug antibody (ADA) incidence (seroconverted ADA or boosted ADA from pre-existing level) were low, and when present, had no noticeable impact on the PK/PD, efficacy, or safety profile of pegcetacoplan. Throughout Study APL2-302, 2 out of 80 patients developed anti-pegcetacoplan peptide antibodies. Both patients also tested positive for neutralizing antibody (NAb). NAb response had no apparent impact on PK or clinical efficacy. Six out of 80 patients developed anti-PEG antibody incidence; 2 were seroconversions and 4 were treatment-boosted.

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 events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il