ASPAVELI

Therapy should be initiated under the supervision of a healthcare professional experienced in the management of patients with haematological or renal disorders. Self-administration and home infusion should be considered for patients who have tolerated treatment well in experienced treatment centres.

The decision of a possibility of self-administration and home infusions should be made after evaluation and recommendation from the treating physician. Posology Pegcetacoplan can be given by a healthcare professional or administered by the patient or caregiver following proper instruction.

PNH Adult patients with PNH Pegcetacoplan is administered twice weekly as a 1 080 mg subcutaneous infusion with a commercially available syringe system infusion pump or on-body delivery system, that can deliver doses up to 20 mL. The twice weekly dose should be administered on Day 1 and Day 4 of each treatment week.

4). Patients with PNH switching to ASPAVELI from a C5 inhibitor For the first 4 weeks, pegcetacoplan is administered as twice weekly subcutaneous doses of 1 080 mg in addition to the patient’s current dose of C5 inhibitor treatment to minimise the risk of haemolysis with abrupt treatment discontinuation.

After 4 weeks, the patient should discontinue C5 inhibitor before continuing on monotherapy with ASPAVELI. Switches from complement inhibitors other than eculizumab have not been studied. 2). , Day 1, Day 4, Day 7, Day 10, Day 13, and so forth) if a patient has a lactate dehydrogenase (LDH) level greater than 2 x upper limit of normal (ULN).

4). C3G and primary IC-MPGN Pegcetacoplan is administered twice weekly as a subcutaneous infusion with a commercially available syringe system infusion pump or on-body delivery system, that can deliver doses up to 20 mL. The twice weekly dose should be administered on Day 1 and Day 4 of each treatment week.

C3G and primary IC-MPGN are chronic diseases. Discontinuation of this medicinal product is not recommended unless clinically indicated. Adult patients with C3G or primary IC-MPGN Pegcetacoplan is administered twice weekly as a 1 080 mg subcutaneous infusion.

Adolescent patients with C3G or primary IC-MPGN For adolescent patients, the dosing regimen is based on the patient´s body weight and consists of the following: Body weight First dose (infusion volume) Second dose (infusion volume) Maintenance dose (infusion volume) ≥ 50 kg 1 080 mg twice weekly (20 mL) 35 to < 50 kg 648 mg (12 mL) 810 mg (15 mL) 810 mg twice weekly (15 mL) 30 to < 35 kg 540 mg (10 mL) 540 mg (10 mL) 648 mg twice weekly (12 mL) Missed dose If a dose of pegcetacoplan for treatment of PNH, C3G or primary IC-MPGN is missed, it should be administered as soon as possible, then the regular schedule should be resumed even if this results in an interval of less than 3 days between the replacement dose and the subsequent dose.

Summary of the safety profile PNH The most commonly reported adverse reactions in patients with PNH treated with pegcetacoplan 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, pyrexia, cough, urinary tract infection, vaccination complication, pain in extremity, dizziness, arthralgia, and back pain.

The most commonly reported serious adverse reactions were haemolysis and sepsis. C3G and primary IC-MPGN The most commonly reported adverse drug reactions in patients with C3G or primary IC-MPGN treated with pegcetacoplan were infusion site reactions and upper respiratory tract infections.

The most commonly reported serious adverse reactions were acute kidney injury and pneumonia. Tabulated list of adverse reactions Table 1 gives the adverse reactions observed from clinical studies and postmarketing experience with pegcetacoplan in patients with PNH, C3G and primary IC-MPGN.

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 Adverse reaction Frequency in PNH Frequency in C3G or primary IC- MPGN Infections and infestations Influenza Very common Upper respiratory tract infections2 Very common Very common Urinary tract infection Very common Common Sepsis Common3 Opportunistic infections Common4 COVID-19, Gastrointestinal infection, Fungal infection, Skin infection, Oral infection Common Ear infection Common Common Infection, Respiratory tract infection5, Viral infection, Bacterial infection, Vaginal infection, Eye infection Common Cervicitis, Groin infection Uncommon Pneumonia Uncommon Common Nasal abscess, Tuberculosis, Oesophageal candidiasis, COVID-19 pneumonia, Anal abscess Uncommon Immune system disorders Hypersensitivity reaction Very common6 Anaphylactic reaction7 Anaphylactic shock7 Uncommon Blood and lymphatic system disorders Haemolysis Very common Thrombocytopenia Common Common8 Neutropenia Common Common Metabolism and nutrition disorders Hypokalaemia Common Common Nervous system disorders Headache Very common Very common Dizziness Very common Vascular disorders Hypertension Common Respiratory, thoracic and mediastinal disorders Cough Very common Common Dyspnoea, Oropharyngeal pain, Nasal congestion Common Epistaxis Common Common Gastrointestinal disorders Abdominal pain Very common Diarrhoea Very common Very common Nausea Common Very common Skin and subcutaneous tissue disorders Erythema, Rash, Urticaria Common Musculoskeletal and connective tissue disorders Arthralgia, Back pain Very common Pain in extremity Very common Common Myalgia Common Common Muscle spasms Common Renal and urinary disorders Acute kidney injury Common Very common Chromaturia Common General disorders and administration site conditions Pyrexia Very common Very common Fatigue Very common Common Infusion site reactions9 Very common Very common Investigations Alanine aminotransferase increased, Bilirubin increased Common Injury, poisoning and procedural complications Vaccination complication Very common 1 Studies APL2-308, APL2-302, APL2-202, APL2-CP-PNH-204, and APL-CP0514 in PNH patients and Study APL2-C3G-310, APL2-C3G-314, APL2-201 and APL2-C3G-204 in C3G and primary IC-MPGN patients.

Serious infections caused by encapsulated bacteria The use of pegcetacoplan may predispose individuals to serious infections caused by encapsulated bacteria including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.

To reduce the risk of infection, all patients must be vaccinated against these bacteria according to applicable local guidelines at least 2 weeks prior to receiving pegcetacoplan, unless the risk of delaying therapy outweighs the risk of developing an infection.

Patients with known history of vaccination Before receiving treatment with pegcetacoplan in patients with a known history of vaccination, it should be ensured that patients have received vaccines against encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae Type B within 2 years prior to starting pegcetacoplan.

Patients without known history of vaccination For patients without known history of vaccination, the required vaccines should be administered at least 2 weeks prior to receiving the first dose of pegcetacoplan. If immediate therapy is indicated, the required vaccines should be administered as soon as possible and the patient treated with appropriate antibiotics until 2 weeks after vaccination.

Monitoring patients for serious infections Vaccination may not be sufficient to prevent serious infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents. All patients should be monitored for early signs of infections caused by encapsulated bacteria including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, evaluated immediately if infection is suspected, and treated with appropriate antibiotics if necessary.

Patients should be informed of these signs and symptoms, and steps taken to seek medical care immediately. Physicians must discuss the benefits and risks of pegcetacoplan therapy with patients. Hypersensitivity Hypersensitivity reactions have been reported.

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