Kanuma

HOS-097479 · has-adverse-reaction-information · PDF-Seite 5

Summary of safety profile The data described below reflect the exposure to sebelipase alfa in 125 patients at doses ranging from 0.35 mg/kg once every other week to 7.5 mg/kg once weekly in clinical studies (see section 5.1), with a treatment duration range from 1 day to 60.5 months (5 years). 5 Of the 106 children and adults enrolled in clinical studies, 102 (96.2%) have received sebelipase alfa at a dosage regimen of 1 mg/kg once every other week, with a median duration of exposure of 33 months (6, 59 months). The median duration of exposure for the 19 infants enrolled in clinical studies was 35.5 months (1 day to 60 months). The most serious adverse reactions experienced by 4% of patients in clinical studies were signs and symptoms consistent with anaphylaxis. Signs and symptoms included chest discomfort, conjunctival hyperaemia, dyspnoea, hyperaemia, eyelid oedema, rhinorrhoea, severe respiratory distress, tachycardia, tachypnoea, irritability, flushing, pruritus, urticaria, stridor, hypoxia, pallor and diarrhoea. Tabulated list of adverse reactions The data in Table 1 describe adverse reactions reported in infants who received sebelipase alfa in clinical studies. The data in Table 2 describe adverse reactions reported in children and adults who received sebelipase alfa in clinical studies. Adverse reactions are listed by system organ class (SOC) and frequency. Frequencies are defined 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) and not known (cannot be estimated from the available data). Table 1: Adverse reactions reported in infants receiving sebelipase alfa (N = 19 patients) MedDRA System organ class MedDRA Preferred Term Frequency Hypersensitivitya Very common Immune system disorders Anaphylactic reactionb Eye Disorders Eyelid oedema Very common Cardiac disorders Tachycardia Very common Respiratory, thoracic and mediastinal Very common Respiratory distress disorders

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HOS-097475 · has-contraindication-information · PDF-Seite 4

Life-threatening hypersensitivity (anaphylactic reaction) to the active substance when attempts to rechallenge are unsuccessful, or to egg or any of the excipients listed in section 6.1, (see section 4.4).

HOS-097474 · has-indication-information · PDF-Seite 2

KANUMA is indicated for long-term enzyme replacement therapy (ERT) in patients of all ages with lysosomal acid lipase (LAL) deficiency.

HOS-097477 · has-interaction-information · PDF-Seite 5

No interaction studies have been performed. Because it is a recombinant human protein, sebelipase alfa is an unlikely candidate for cytochrome P450 mediated or other drug-drug interactions.

HOS-097478 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no or limited data from the use of sebelipase alfa in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid use of sebelipase alfa during pregnancy. Breast-feeding There are no data from studies in breast-feeding women. It is not known whether sebelipase alfa is excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from sebelipase alfa therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no clinical data on the effects of sebelipase alfa on fertility. Animal studies show no evidence of impaired fertility (see section 5.3).

HOS-097476 · has-warning-information · PDF-Seite 4

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 including anaphylaxis Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with sebelipase alfa; see section 4.8. Therefore, appropriate medical support must be readily available when sebelipase alfa is administered. If severe reactions occur, the sebelipase alfa infusion should be immediately stopped and appropriate medical treatment should be initiated. The risks and benefits of re-administering sebelipase alfa following a severe reaction should be considered. Following the first sebelipase alfa infusion, including the first infusion after a dose escalation, patients should be observed for 1 hour in order to monitor for any signs or symptoms of anaphylaxis or a severe hypersensitivity reaction. The management of hypersensitivity reactions may include temporarily interrupting the infusion, lowering the infusion rate, and/or treatment with antihistamines, antipyretics, and/or corticosteroids. For patients who have experienced allergic reactions during infusion, caution should be exercised upon re-administration. If interrupted, the infusion may be resumed at a slower rate with increases as tolerated. Pre-treatment with antipyretics and/or antihistamines may prevent subsequent reactions in those cases where symptomatic treatment was required. In cases of severe infusion reactions and in cases of lack or loss of effect, patients should be tested for the presence of antibodies. This medicinal product may contain traces of egg proteins. Patients with known egg allergies were excluded from clinical studies (see section 4.3). Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. In the sebelipase alfa clinical program, patients were routinely tested for anti-sebelipase alfa anti-drug antibodies (ADAs) to determine the immunogenicity potential of sebelipase alfa. Patients who tested positive for ADAs were also tested for inhibitory antibody activity. The presence of inhibitory activity has been detected at some postbaseline timepoints in clinical studies (see section 4.8). Overall, no conclusion on the relationship between development of ADAs/NAbs and associated hypersensitivity reactions or suboptimal clinical response can be made. 4 I

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