Soliris

Soliris must be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with haematological, renal, neuromuscular or neuro- inflammatory disorders. Home infusion may be considered for patients who have tolerated infusions well in the clinic.

The decision of a patient to receive home infusions should be made after evaluation and recommendation from the treating physician. Home infusions should be performed by a qualified healthcare professional. 3 Posology Paroxysmal Nocturnal Haemoglobinuria (PNH) in adults The PNH dosing regimen for adult patients (≥18 years of age) consists of a 4-week initial phase followed by a maintenance phase: • Initial phase: 600 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 minutes) intravenous infusion every week for the first 4 weeks.

1). atypical Haemolytic Uremic Syndrome (aHUS), refractory generalized Myasthenia Gravis (gMG) and Neuromyelitis Optica Spectrum Disorder (NMOSD) in adults The aHUS, refractory gMG and NMOSD dosing regimen for adult patients (≥18 years of age) consists of a 4 week initial phase followed by a maintenance phase: • Initial phase: 900 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 minutes) intravenous infusion every week for the first 4 weeks.

1). Refractory gMG Available data suggest that clinical response is usually achieved by 12 weeks of Soliris treatment. Discontinuation of the therapy should be considered in a patient who shows no evidence of therapeutic benefit by 12 weeks.

Paediatric patients in PNH, aHUS, or refractory gMG Paediatric PNH, aHUS, or refractory gMG patients with body weight ≥ 40 kg are treated with the adult dosing recommendations. In paediatric PNH, aHUS, and refractory gMG patients with body weight below 40 kg, the Soliris dosing regimen consists of: Patient Body Weight Initial Phase Maintenance Phase 30 to <40 kg 600 mg weekly for the first 2 weeks 900 mg at week 3; then 900 mg every 2 weeks 20 to <30 kg 600 mg weekly for the first 2 weeks 600 mg at week 3; then 600 mg every 2 weeks 10 to <20 kg 600 mg single dose at week 1 300 mg at week 2; then 300 mg every 2 weeks 5 to <10 kg 300 mg single dose at week 1 300 mg at week 2; then 300 mg every 3 weeks Soliris has not been studied in patients with PNH or refractory gMG who weigh less than 40kg.

The posology of Soliris to be used in paediatric patients with PNH or refractory gMG patients weighing less than 40 kg is identical to the weight-based dose recommendation provided for paediatric patients with aHUS. Based on the pharmacokinetic (PK)/pharmacodynamic (PD) data available in patients with aHUS and PNH treated with Soliris, this body-weight based dose regimen for paediatric patients is expected to result in an efficacy and safety profile similar to that in adults.

Summary of the safety profile Supportive safety data were obtained from 33 clinical studies that included 1,555 patients exposed to eculizumab in complement-mediated disease populations, including PNH, aHUS, refractory gMG and NMOSD.

The most common adverse reaction was headache, (occurred mostly in the initial phase of dosing), and the most serious adverse reaction was meningococcal infection. Tabulated list of adverse reactions Table 1 gives the adverse reactions observed from spontaneous reporting and in eculizumab completed clinical trials, including PNH, aHUS, refractory gMG and NMOSD studies.

Adverse reactions reported at a 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) or not known (cannot be estimated from the available data) frequency with eculizumab, are listed by system organ class and preferred term.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 11 Table 1: Adverse Reactions reported in eculizumab clinical trials, including patients with PNH, aHUS, refractory gMG and NMOSD as well as from postmarketing experience MedDRA System Organ Class Very Common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1 000 to <1/100) Rare (≥1/10000 to <1/1000) Not known (cannot be estimated from the available data) Infection and infestations Pneumonia, Upper respiratory tract infection, Bronchitis, Nasopharyngitis, Urinary tract infection, Oral Herpes Meningococcal infectionb, Sepsis, Septic shock, Peritonitis, Lower respiratory tract infection, Fungal infection, Viral infection, Abscessa, Cellulitis, Influenza, Gastrointestinal infection, Cystitis, Infection, Sinusitis, Gingivitis Aspergillus infectionc, Arthritis bacterialc, Genitourinary tract gonococcal infection, Haemophilus infection, Impetigo Neoplasms benign, malignant and unspecified (including cysts and polyps) Malignant melanoma, Myelodysplastic syndrome Blood and lymphatic system disorders Leukopenia, Anaemia Thrombocytopenia, Lymphopenia Haemolysis*, Abnormal clotting factor, Red blood cell agglutination, Coagulopathy Immune system disorders Anaphylactic reaction, Hypersensitivity Endocrine disorders Grave’s disease Metabolism and nutrition disorders Decreased appetite Psychiatric disorders Insomnia Depression, Anxiety, Mood swings, Sleep disorder Abnormal dreams Nervous system disorders Headache Dizziness Paraesthesia, Tremor, Dysgeusia, Syncope Eye disorders Vision blurred Conjunctival irritation Ear and labyrinth disorders Tinnitus, Vertigo Cardiac disorders Palpitation Vascular disorders Hypertension Accelerated hypertension, Hypotension, Hot flush, Vein disorder Haematoma Respiratory, thoracic and mediastinal disorders Cough, Oropharyngeal pain Dyspnoea, Epistaxis, Throat irritation, Nasal congestion, Rhinorrhoea Gastrointestinal disorders Diarrhoea, Vomiting, Nausea, Abdominal pain Constipation, Dyspepsia, Abdominal distension Gastroesophageal reflux disease, Gingival pain Hepatobiliary disorders Alanine aminotransferase increased, Aspartate Jaundice Liver injuryd 12 aminotransferase increased, Gamma- glutamyltransferase increased Skin and subcutaneous tissue disorders Rash, Pruritus, Alopecia Urticaria, Erythema, Petechiae, Hyperhidrosis, Dry skin, Dermatitis Skin depigmentation Musculoskeletal and connective tissue disorders Arthralgia, Myalgia, Pain in extremity Muscle spasms, Bone pain, Back pain, Neck pain Trismus, Joint swelling Renal and urinary disorders Renal impairment, Dysuria, Haematuria Reproductive system and breast disorders Spontaneous penile erection Menstrual disorder General disorders and administration site conditions Pyrexia, Fatigue, Influenza-like illness Edema, Chest discomfort, Asthenia, Chest pain, Infusion site pain, Chills Extravasation, Infusion site paraesthesia, Feeling hot Investigations Haematocrit decreased, Haemoglobin decreased Coombs test positivec Injury, poisoning and procedural complication Infusion-related reaction Included Studies: Asthma (C07-002), aHUS(C08-002, C08-003, C10-003, C10-004), Dermatomyositis (C99-006), refractory gMG (C08-001, ECU-MG-301, ECU-MG-302, ECU-MG-303), Neuromyelitis Optica Spectrum Disorder (ECU-NMO-301, ECU-NMO-302), IMG (C99-004, E99-004), PNH (C02-001, C04-001, C04-002, C06-002, C07- 001, E02-001, E05-001, E07-001, M07-005, X03-001, X03-001A), Psoriasis (C99-007), RA (C01-004, C97-001, C99-001, E01-004, E99-001), STEC-HUS (C11-001), SLE (C97-002).

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. Soliris is not expected to affect the aplastic component of anaemia in patients with PNH.

Meningococcal Infection Due to its mechanism of action, the use of Soliris increases the patient’s susceptibility to meningococcal infection (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur. To reduce the risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving Soliris unless the risk of delaying Soliris therapy outweighs the risks of developing a meningococcal infection.

Patients who initiate Soliris treatment less than 2 weeks after receiving a tetravalent meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines against all available serogroups including A, C, Y, W 135 and B, are recommended in preventing the commonly pathogenic meningococcal serogroups.

Patients must be vaccinated and revaccinated according to current national guidelines for vaccination use. Vaccination may further activate complement. As a result, patients with complement-mediated diseases, including PNH, aHUS, refractory gMG and NMOSD, may experience increased signs and symptoms of their underlying disease, such as haemolysis (PNH), TMA (aHUS), MG exacerbation (refractory gMG) or 6 relapse (NMOSD).

Therefore, patients should be closely monitored for disease symptoms after recommended vaccination. Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Cases of serious or fatal meningococcal infections have been reported in Soliris-treated patients. 8). All patients should be monitored for early signs of meningococcal infection, evaluated immediately if infection is suspected, and treated with appropriate antibiotics if necessary.

1. 4): - with unresolved Neisseria meningitidis infection - who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination.