Version July 2025
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement and after extended duration of therapy. Initiate sebelipase alfa in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (eg, anaphylaxis) occurs, discontinue sebelipase and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.
Dosage guidance:
Safety: Administer in health care setting with appropriate monitoring and support, including cardiopulmonary resuscitation equipment.
Clinical considerations: Consider pretreatment with antihistamines and/or antipyretics for prevention of subsequent infusion reactions in patients with previous hypersensitivity reactions to sebelipase alfa or other enzyme replacement therapies.
Lysosomal acid lipase (LAL) deficiency; rapidly progressive presenting within the first 6 months of life:
Infants, Children, and Adolescents: IV: Initial: 1 mg/kg/dose once weekly; may increase to 3 mg/kg/dose once weekly if response not optimal; if response remains not optimal may further increase to 5 mg/kg/dose once weekly. Suboptimal response may include poor growth, deteriorating biochemical markers, or persistent/worsening organomegaly.
Lysosomal acid lipase (LAL) deficiency: Infants, Children, and Adolescents: IV: Initial: 1 mg/kg/dose every other week; may increase to 3 mg/kg/dose every other week if response not optimal. Suboptimal response may include poor growth and deteriorating biochemical markers (eg, ALT, AST) and/or parameters of lipid metabolism (eg, LDL-C, triglycerides).
Dosing adjustment for toxicity:
Infants, Children, and Adolescents:
Mild or moderate hypersensitivity reaction: Interrupt infusion; consider resuming at slower infusion rate. Consider pretreatment with antihistamines and/or antipyretics for prevention of subsequent infusion reactions.
Severe hypersensitivity reaction or anaphylaxis: Immediately discontinue infusion and initiate appropriate medical care.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Sebelipase alfa: Drug information")
Dosage guidance:
Clinical considerations: Pretreatment with antihistamines and/or antipyretics can be considered for prevention of subsequent infusion reactions in patients with previous hypersensitivity reactions to sebelipase alfa or other enzyme replacement therapies; during clinical studies, patients were not routinely premedicated prior to infusion.
Lysosomal acid lipase deficiency: IV: 1 mg/kg every other week; may increase to 3 mg/kg every other week in patients with suboptimal response (poor growth, deteriorating biochemical markers [eg, ALT, AST], and/or parameters of lipid metabolism [eg, low-density lipoprotein cholesterol, triglycerides]).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences are reported for pediatric patients and adults unless specified otherwise.
>10%:
Cardiovascular: Tachycardia (infants)
Dermatologic: Urticaria (infants)
Endocrine & metabolic: Increase in LDL cholesterol (children, adolescents, adults), increased serum triglycerides (children, adolescents, adults)
Gastrointestinal: Diarrhea, vomiting (infants)
Hematologic & oncologic: Anemia (infants)
Hypersensitivity: Hypersensitivity reaction
Immunologic: Antibody development (may be neutralizing)
Nervous system: Headache (children, adolescents, adults)
Respiratory: Cough (infants), nasopharyngitis, oropharyngeal pain (children, adolescents, adults), respiratory distress (infants), rhinitis (infants)
Miscellaneous: Fever
1% to 10%:
Gastrointestinal: Abdominal pain (children, adolescents, adults), constipation (children, adolescents, adults), nausea (children, adolescents, adults)
Hypersensitivity: Anaphylaxis (infants)
Nervous system: Asthenia (children, adolescents, adults), dizziness (children, adolescents, adults)
Frequency not defined (any population):
Cardiovascular: Chest discomfort
Gastrointestinal: Retching
Nervous system: Anxiety, hypotonia
Respiratory: Oxygen saturation decreased, sneezing
There are no contraindications listed within the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to sebelipase alfa or any component of the formulation.
Concerns related to adverse effects:
• Anaphylaxis/Hypersensitivity reactions: Sebelipase alfa may cause severe hypersensitivity reactions, including anaphylaxis (sometimes life-threatening). Most hypersensitivity reactions reported have occurred during infusion and within 4 hours after the infusion. Anaphylaxis has occurred early during therapy and after extended use. Other more common reactions included abdominal pain, agitation, chills, diarrhea, eczema, edema, fever, hypertension, irritability, laryngeal edema, nausea, pallor, pruritus, rash, and vomiting. Management of reaction depends on the severity of the reaction; discontinue sebelipase if anaphylaxis or other severe reactions occur and initiate appropriate medical treatment including epinephrine; may also be managed by interrupting infusion, slowing infusion rate, and/or use of antihistamines, antipyretics, and/or corticosteroids. Consider pretreatment with antihistamines and/or antipyretics for prevention of subsequent infusion reactions in patients with previous hypersensitivity reactions to sebelipase alfa or other enzyme replacement therapies.
• Antibody formation: Patients have developed anti-drug antibodies (ADA) to sebelipase alfa and may be more likely to experience hypersensitivity reactions. Some patients with neutralizing antibodies experienced decreased growth velocity. No clear association exists between the development of ADA and decreased efficacy in patients.
Dosage form specific issues:
• Allergy to egg or egg products: Sebelipase alfa is produced in egg whites of genetically engineered chickens; consider the risks and benefits in patients with known systemic hypersensitivity reactions to eggs or egg products.
From clinical trials, the reported incidence of hypersensitivity reactions was 20% for all patients (21 of 106 patients); however, the incidence in the infant age group was 64% (nine of 14 patients); patients were not premedicated prior to sebelipase alfa infusions during the trials.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Kanuma: 20 mg/10 mL (10 mL) [contains albumin human, egg white (egg protein)]
No
Solution (Kanuma Intravenous)
20 mg/10 mL (per mL): $1,225.20
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Kanuma: 20 mg/10 mL (10 mL) [contains albumin human, egg white (egg protein)]
Parenteral: IV infusion: Administer diluted solution (0.1 to 1.5 mg/mL) using low-protein-binding infusion set with in-line, low-protein-binding 0.2 micron filter. Infuse IV over at least 2 hours; may consider 1-hour infusion for those patients receiving 1 mg/kg dose who tolerate a 2-hour infusion. Consider further prolonging infusion time for doses >1 mg/kg/dose or in patients who have experienced a hypersensitivity reaction.
IV: Administer diluted solution as an IV infusion using low-protein-binding infusion set with in-line, low-protein-binding 0.2 micron filter. Infuse over at least 2 hours; may consider 1-hour infusion for those patients receiving 1 mg/kg dose who tolerate a 2-hour infusion. Consider further prolonging infusion time for doses >1 mg/kg or if hypersensitivity reaction occurs.
Store intact vials under refrigeration between 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not shake or freeze. If not used immediately, reconstituted product may be stored up to 24 hours in the refrigerator.
Treatment of patients with lysosomal acid lipase (LAL) deficiency (FDA approved in ages ≥1 month and adults).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
There are no known significant interactions.
Adverse events were not observed in animal reproduction studies. Sebelipase alfa is a recombinant form of lysosomal acid lipase (LAL), an essential enzyme required for lipid metabolism (Burton 2015; Shirley 2015).
Signs and symptoms of hypersensitivity reactions including anaphylaxis (during infusion and for at least 4 hours after completion of infusion); lipid panel (eg, LDL-C, triglycerides); antidrug antibody assessment; hepatic function (eg, ALT, AST); growth parameters.
Sebelipase alfa binds to cell surface receptors via glycans expressed on the protein and is subsequently internalized into lysosomes. Sebelipase alfa catalyzes the lysosomal hydrolysis of cholesteryl esters and triglycerides to free cholesterol, glycerol, and free fatty acids. In patients with lysosomal acid lipase (LAL) deficiency, replacement with sebelipase alfa, a recombinant form of LAL, results in improvement in disease-related hepatic and lipid parameters.
Onset:
LDL-c and triglycerides reduction: Within 8 weeks; a transient increase in these values occurs during first 2 to 4 weeks of treatment
ALT reduction: Within 2 weeks.
Duration: Effects on ALT partially reverse 3 weeks after treatment discontinuation (Balwani 2013)
Distribution: Vd:
Pediatric patients:
4 to 11 years: 3.6 ± 3 L
12 to 17 years: 5.4 ± 2.4 L
Adults: 5.3 ± 1.6 L
Half-life elimination: Children ≥4 years, Adolescents, and Adults: Mean range: 5.4 to 6.6 minutes
Time to peak, serum: Children ≥4 years, Adolescents, and Adults: Mean range: 1.1 to 1.3 hours
