Alhemo

Treatment should be initiated under the supervision of a physician experienced in treatment of haemophilia and/or bleeding disorders. Posology Treatment should be initiated in a non-bleeding state. Treatment with rFVIIa should be discontinued at least 12 hours before starting concizumab therapy and treatment with aPCC should be discontinued at least 48 hours before.

The prophylactic use of factor VIII (FVIII) and factor IX (FIX) products should be discontinued two half-lives before initiating prophylaxis with concizumab. No clinical trial data are available to guide switching patients from non- replacement therapies to concizumab.

A wash-out interval of approximately 5 half-lives of the prior therapy, based on the half-life specified in the respective SmPC, could be considered before initiating prophylaxis with concizumab. Haemostatic support with factor products or bypassing agents may be needed during the switch from non-factor-based products.

The recommended dosing regimen is • Day 1: a loading dose of 1 mg/kg once. 20 mg/kg. • 4 weeks after initiation of treatment: measurement of concizumab plasma concentration prior to administration of the next scheduled dose. The measurement must be performed using a validated in vitro diagnostic test.

• When concizumab plasma concentration result is available: individual maintenance dose is set once based on concizumab plasma concentration as indicated below in Table 1. 15 mg/kg Individual maintenance dose setting should be performed at the earliest convenience (after concizumab plasma concentration result is available) and recommended no later than 8 weeks after initiation of treatment.

Additional concizumab plasma concentration measurement(s) can be taken after 8 weeks on the same maintenance dose according to the patient’s medical condition. For example, this should be considered if a patient experiences an increased bleeding frequency, a large change in body weight, has missed doses before maintenance dose setting, or acquires a comorbidity, which can lead to an increase in the overall thromboembolic risk.

Since concizumab is dosed per body weight (mg/kg), it is important to recalculate the dose (mg) when the body weight changes. 25 mg/kg) = total amount (mg) of concizumab to be administered. 5 mL and 300 mg/3 mL pre-filled pens (gold).

Summary of the safety profile The overall safety profile of concizumab is based on data from clinical trials. 3%). Tabulated list of adverse reactions The following adverse reactions are based on data from post-marketing surveillance and pooled data from the clinical trials NN7415-4159 (phase 1b), NN7415-4310 (phase 2), NN7415-4255 (phase 2), NN7415-4311 (phase 3) and NN7415-4307 (phase 3), in which a total of 320 male patients with haemophilia A with and without inhibitors and haemophilia B with and without inhibitors received at least one dose of concizumab as routine prophylaxis.

The patients were exposed for a total of 475 exposure years in clinical trials. Table 2 presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level). Frequencies have been evaluated according to the following convention: 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), not known (cannot be estimated from the available data).

Table 2 Adverse reactions from pooled clinical trials with concizumab System Organ Class Adverse reaction Frequency Immune system disorders Hypersensitivity Common Vascular disorders Thromboembolic events Uncommon General disorders and administration site disorders Injection site reactions Very common Description of selected adverse reactions Injection site reactions Injection site reactions were reported across the multiple dose clinical trials.

1%). The majority were reported as mild. Paediatric population 78 of the clinical trial participants were adolescents (≥ 12 to < 18 years). The safety profile was similar between adolescent and adult patients and as expected for the age group.

The safety and efficacy of concizumab in children aged below 12 years have not yet been established. No data are available. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

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. Hypersensitivity reactions Allergic type hypersensitivity reactions have occurred with concizumab within the initial weeks of treatment, including hospitalisation and permanent discontinuation of therapy.

Patients should be informed of the signs of acute hypersensitivity reactions. If symptoms of hypersensitivity occur, the patient should be advised to discontinue the use of Alhemo and contact the physician who should ensure appropriate treatment.

1). g. increase in breakthrough bleeding events) should be evaluated to assess the etiology and other therapeutic options should be considered if neutralising anti-concizumab antibodies are suspected. Thromboembolic events Cases of non-fatal arterial and venous thromboembolic events have been reported in the concizumab clinical trials.

8). Patients treated with concizumab should be informed of and monitored for the occurrence of signs and symptoms of thromboembolic events. In case of suspicion of thromboembolic events, concizumab should be discontinued, and further investigations and appropriate medical treatment should be initiated.

There should be careful consideration whether the potential benefit of concizumab treatment outweighs the potential risk in patients considered at high risk of thromboembolic events. This consideration should be re-evaluated periodically.

, advanced atherosclerotic disease, crush injury, cancer or septicaemia), there may be a risk of thromboembolic events or disseminated intravascular coagulation (DIC). In these situations, the potential benefit of treatment with concizumab should be weighed against the risk of these complications.

Effects of concizumab on coagulation tests Concizumab therapy does not produce clinically meaningful changes in standard measures of coagulation including activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT). Excipients This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

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