KANUMA

/ Alexion

Patients with Rapidly Progressive LAL Deficiency presenting within the first 6 months of life the recommended starting dose in infants (< 6 months of age) presenting with rapidly progressive LAL deficiency is either 1 mg/kg or 3 mg/kg administered as an intravenous infusion once weekly, depending on the clinical status of the patient. A higher starting dose of 3 mg/kg should be considered based on the severity of the disease and rapid disease progression.
Dose escalation should be considered based on suboptimal response to clinical and biochemical criteria, including, e.g., poor growth, deteriorating biochemical markers (e.g. liver transaminases, ferritin, C-reactive Protein, and coagulation parameters), persistent or worsening organomegaly, increased frequency of
intercurrent infections, and persistent worsening of other symptoms (e.g. gastrointestinal symptoms):
– a dose escalation to 3 mg/kg should be considered in case of suboptimal clinical response;
– a further dose escalation up to 5 mg/kg should be considered in case of persistent
suboptimal clinical response.
Further dose adjustments, as a reduction of the dose or an extension of the dose interval, can be made on an individual basis based on achievement and maintenance of therapeutic goals.
Clinical studies evaluated doses ranging from 0.35 to 5 mg/kg once weekly, with one patient receiving a higher dose of 7.5 mg/kg once weekly.
See prescribing information for full details.

Long-term enzyme replacement therapy (ERT) in patients of all ages
with lysosomal acid lipase (LAL) deficiency.

Life-threatening hypersensitivity (anaphylactic reaction) to the active substance when attempts to rechallenge are unsuccessful, or to egg or any of the excipients

Hypersensitivity reactions including anaphylaxis:
Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with sebelipase alfa. 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.
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. Overall, no conclusion on the relationship between development of ADAs/NAbs and associated hypersensitivity reactions
or suboptimal clinical response can be made.
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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.
See prescribing information for full details.

No interaction studies have been performed.

Pregnancy: There are no or limited data from the use of sebelipase alfa in pregnant women. As a precautionary measure, it is preferable to avoid use of sebelipase alfa
during pregnancy.
Lactation: 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 breastfeeding for the child and the benefit of therapy for the woman.