Sebelipase Alfa (Monograph)

Brand name: Kanuma
Drug class: Enzymes

Medically reviewed by Drugs.com on Jul 10, 2025. Written by ASHP.

Warning

Anaphylaxis reported to occur during early course of enzyme replacement therapy and after extended duration of therapy.¹
Initiate sebelipase alfa therapy under supervision of a clinician in a setting with appropriate medical monitoring and support measures.¹
If severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue therapy and immediately initiate appropriate medical treatment, including epinephrine administration.¹

Introduction

Biosynthetic (recombinant DNA origin) form of human lysosomal acid lipase.¹ ⁵

Uses for Sebelipase Alfa

Lysosomal Acid Lipase Deficiency

Treatment of lysosomal acid lipase deficiency¹ ⁷ ¹¹ ¹² (designated an orphan drug by FDA for this use).²

Survival benefit demonstrated in patients with rapidly progressive infantile-onset disease (i.e., Wolman disease).¹ ⁸ ⁹

In pediatric patients and adults with late-onset disease (i.e., cholesterol ester storage disease), improvements in disease-related lipid and hepatic abnormalities demonstrated.¹ ⁷

Sebelipase Alfa Dosage and Administration

General

Dispensing and Administration Precautions

Initiate sebelipase alfa therapy under the supervision of a clinician knowledgeable in the management of hypersensitivity reactions in a setting with appropriate medical monitoring and support measures.¹

Administration

IV Administration

Administer by IV infusion.¹

Administer using an inline, low-protein-binding 0.2-µm filter.¹

Contains no preservatives; use immediately following preparation.¹ Discard any unused portions.¹

Dilution

Prior to administration, must dilute commercially available sebelipase alfa injection concentrate.¹

Determine number of vials to be diluted based on patient’s weight and recommended dose of 1, 3, or 5 mg/kg.¹

Remove required number of vials from refrigerator and allow to reach room temperature; do not shake.¹ Withdraw appropriate dose from vials and dilute with 0.9% sodium chloride injection to prepare a final concentration of 0.1–1.5 mg/mL.¹

See Table 1 for recommended total infusion volumes based on patient's weight and prescribed dose.¹

Table 1: Total Infusion Volumes1
Patient Weight (kg)	Total Infusion Volume (mL) for 1-mg/kg Dose	Total Infusion Volume (mL) for 3-mg/kg Dose	Total Infusion Volume (mL) for 5-mg/kg Dose
1–2.9	4	8	12
3-5.9	6	12	20
6–10.9	10	25	50
11-24.9	25	50	150
25-49.9	50	100	250
50–99.9	100	250	500
100–120.9	250	500	600

Mix diluted solution gently; do not shake.¹ The solution should appear clear to slightly opalescent and colorless to slightly colored; thin translucent fibers or particles may be present.¹ Do not administer if solution appears cloudy or if other particulate matter observed.¹

Rate of Administration

Infuse over at least 2 hours.¹ Consider longer infusion times in patients receiving dosages greater than 1 mg/kg or in patients who experience hypersensitivity reactions.¹ Consider shorter infusion time of 1 hour, if tolerated, in patients receiving a dose of 1 mg/kg.¹

Dosage

Pediatric Patients

Lysosomal Acid Lipase Deficiency

Infants with Rapidly Progressive Lysosomal Acid Lipase Deficiency Presenting Within the First 6 Months of Life

1 mg/kg once weekly.¹ In patients not achieving optimal clinical response, may increase to 3 mg/kg once weekly.¹ In patients with continued suboptimal response at 3 mg/kg once weekly, may increase to 5 mg/kg once weekly.¹

Suboptimal response defined as presence of any of the following: poor growth, deteriorating biochemical markers, or persistent or worsening organomegaly.¹

Pediatric Patients with Lysosomal Acid Lipase Deficiency

1 mg/kg once every other week.¹ In patients not achieving optimal clinical response, may increase to 3 mg/kg once every other week.¹

Suboptimal response defined as presence of any of the following: poor growth, deteriorating biochemical markers, and/or lipid metabolism parameters.¹

Adults

Lysosomal Acid Lipase Deficiency

IV

1 mg/kg once every other week.¹ In patients not achieving optimal clinical response, may increase to 3 mg/kg once every other week.¹

Suboptimal response defined as presence of any of the following: poor growth, deteriorating biochemical markers, and/or lipid metabolism parameters.¹

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Sebelipase Alfa

Contraindications

None.¹

Warnings/Precautions

Warnings

Hypersensitivity Reactions Including Anaphylaxis

Life-threatening hypersensitivity reactions, including anaphylaxis, reported (see Boxed Warning).¹ Generally during or within 4 hours of the infusion.¹ Anaphylaxis reported as early as the sixth infusion to as late as 1 year after treatment initiation.¹

Anaphylaxis reported during both early course and extended duration of sebelipase alfa therapy.¹ Initiate therapy under supervision of a clinician with knowledge in the management of hypersensitivity reactions, including anaphylaxis, in a setting with appropriate medial monitoring and support measures.¹ Closely observe patients during and after administration.¹

Manage hypersensitivity reactions based on severity.¹ If anaphylaxis or other severe hypersensitivity reaction occurs, discontinue sebelipase alfa immediately and initiate appropriate medical treatment.¹ For hypersensitivity reactions of lesser severity, may temporarily interrupt infusion, lower infusion rate, and/or administer antihistamines, antipyretics, and/or corticosteroids.¹ If infusion is interrupted, resume at a slower rate; subsequently increase rate as tolerated.¹

To prevent subsequent reactions in patients experiencing hypersensitivity, may consider premedication with antipyretics and/or antihistamines.¹ Consider risks and benefits of retreatment following a severe hypersensitivity reaction.¹ If drug is readministered, monitor patient with appropriate resuscitation measures available.¹ Inform patients of symptoms of life-threatening hypersensitivity reactions and instruct to seek immediate medical care if such symptoms occur.¹

Hypersensitivity to Eggs or Egg Products

Consider risks and benefits of treatment in patients with known systemic hypersensitivity reactions to eggs or egg products.¹

Immunogenicity

Development of antibodies, including neutralizing antibodies, to sebelipase alfa reported.¹ ⁷

Specific Populations

Pregnancy

Clinical data insufficient in pregnant women to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes; animal studies have not suggested any evidence of adverse embryofetal effects.¹

Lactation

Not known whether sebelipase alfa is distributed into human milk.¹ Effects on breastfed infant or on milk production also unknown.¹ Consider known benefits of breast-feeding along with mother's need for sebelipase alfa and any potential adverse effects of the drug or disease on the infant.¹

Pediatric Use

Safety and efficacy established in pediatric patients ≥1 month of age.¹

Geriatric Use

Not studied in patients ≥65 years of age.¹ Not known whether geriatric patients respond differently than younger patients.¹

Common Adverse Effects

Most common adverse reactions (≥30%) in infants with rapidly progressive lysosomal acid lipase deficiency presenting within the first 6 months of life receiving sebelipase alfa: Diarrhea, vomiting, fever, rhinitis, anemia, cough, nasopharyngitis, urticaria.¹

Most common adverse reactions (≥8%) in pediatric and adult patients with lysosomal acid lipase deficiency receiving sebelipase alfa: Headache, fever, oropharyngeal pain, nasopharyngitis, asthenia, constipation, nausea.¹

Drug Interactions

Formal drug interaction studies not performed to date.⁸

Sebelipase Alfa Pharmacokinetics

Pharmacokinetic profile of sebelipase alfa is based on data from adults and pediatric patients; pharmacokinetics not characterized in infants.¹⁰

Absorption

Bioavailability

Nonlinear pharmacokinetics; greater than dose-proportional increase in exposure observed at doses of 1–3 mg/kg.¹

No substantial accumulation following repeated dosing.¹

Peak plasma concentrations occur approximately 1.1–1.3 hours after a dose in pediatric patients and adults.¹

Onset

Increased LDL-cholesterol and triglyceride concentrations initially observed within the first 2–4 weeks; such parameters subsequently decreased to below pretreatment levels within 8 weeks of treatment.¹ ⁷ Decreased ALT concentrations typically observed within 2 weeks of treatment.¹ ⁷

Special Populations

Pharmacokinetic profile similar between adolescents and adults.¹

Distribution

Extent

Not known whether sebelipase alfa distributes into milk.¹

Elimination

Half-life

Approximately 6 minutes.¹ ⁹

Half-life similar across pediatric and adult patients of all age groups receiving 1 mg/kg once every other week.¹

Stability

Storage

Parenteral

Injection for IV Infusion

2–8°C.¹ Protect from light.¹ Do not freeze; do not shake.¹

Following dilution, 2–8°C for ≤24 hours if protected from light.¹ Do not freeze.¹

Actions

Biosynthetic (recombinant DNA origin) form of human lysosomal acid lipase.¹ ⁵
Binds to cell surface receptors and subsequently internalized into lysosomes;¹ catalyzes lysosomal hydrolysis of cholesteryl esters and triglycerides to free cholesterol, glycerol, and free fatty acids.¹
Lysosomal acid lipase deficiency causes accumulation of cholesteryl esters and triglycerides in various cells and organs throughout the body leading to clinical manifestations including hepatomegaly, liver disease (e.g., jaundice, steatosis, fibrosis, cirrhosis), increased aminotransferase concentrations, malabsorption, growth failure, dyslipidemia (e.g., elevated LDL-cholesterol and triglyceride concentrations, decreased HDL-cholesterol concentrations), and atherosclerosis.¹ ³ ⁴ ⁵ ⁶ ⁹
Treatment in patients with rapidly progressive infantile-onset lysosomal acid lipase deficiency (i.e., Wolman disease) increased survival rate beyond 12 months of age; treatment in pediatric and adult patients with later-onset disease (i.e., cholesterol ester storage disease) improved lipid parameters and decreased ALT concentrations.¹ ⁷

Advice to Patients

Risk of severe hypersensitivity reactions, including anaphylaxis.¹ Advise patients of the possible signs and symptoms of hypersensitivity reactions, and to seek immediate medical care if such manifestations occur.¹
Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.¹
Advise patients to inform clinicians if they are or plan to become pregnant or plan to breast-feed.¹
Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Sebelipase Alfa
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection concentrate, for IV infusion	2 mg/mL (20 mg)	Kanuma	Alexion

References

1. Alexion Pharmaceuticals. Kanuma (sebelipase alfa) injection, for intravenous use prescribing information. Boston, MA; 2024 Jul.

2. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website. http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm

3. Hoffman EP, Barr ML, Giovanni MA, et al. Lysosomal acid lipase deficiency. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2016.

4. Burton BK, Deegan PB, Enns GM et al. Clinical features of lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr. 2015; 61:619-25. https://pubmed.ncbi.nlm.nih.gov/26252914

5. Reiner Z, Guardamagna O, Nair D et al. Lysosomal acid lipase deficiency--an under-recognized cause of dyslipidaemia and liver dysfunction. Atherosclerosis. 2014; 235:21-30. https://pubmed.ncbi.nlm.nih.gov/24792990

6. Jones SA, Valayannopoulos V, Schneider E et al. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genet Med. 2016; 18:452-8. https://pubmed.ncbi.nlm.nih.gov/26312827

7. Burton BK, Balwani M, Feillet F et al. A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. N Engl J Med. 2015; 373:1010-20. https://pubmed.ncbi.nlm.nih.gov/26352813

8. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 125561Orig1s000: Medical review. From FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/125561Orig1s000MedR.pdf

9. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 125561Orig1s000: Summary Review. From FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/125561Orig1s000SumR.pdf

10. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 125561Orig1s000: Clinical Pharmacology and Biopharmaceutics Review. From FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/125561Orig1s000ClinPharmR.pdf

11. Burton BK, Sanchez AC, Kostyleva M, et al. Long-term sebelipas alfa treatment in childre and adults with lysosomal acid lipase deficiency. JPGN. 2022;74:757-764.

12. Malinova V, Balwani M, Sharma R, et al. Sebelipase alfa for lysosomal acid lipase deficiency: 5-year treatment experience from a phase 2 open-label extension study. Liver Int. 2020;40:2203-2214.

13. Pastores G, Hughes DA. Lysosomal acid lipase deficiency: therapeutic options. Drug Design, Development and Therapy. 2020;14:591-601.