Sebelipase Alfa

LAL deficiency is an autosomal recessive lysosomal storage disorder characterized by a genetic defect resulting in a marked decrease or loss in activity of the lysosomal acid lipase (LAL) enzyme. The primary site of action of the LAL enzyme is the lysosome, where the enzyme normally causes the breakdown of lipid particles, including LDL-c and triglycerides.

• KANUMA ® is indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency. KANUMA ® is a hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency.

• None. None.contraindicated

Administration of KANUMA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. ( 2.1 ) Infants with Rapidly Progressive LAL Deficiency Presenting within the First 6 Months of Life: The recommended starting dosage is 1 mg/kg as an intravenous infusion once weekly. ( 2.2 ) For patients with a suboptimal clinical response, increase the dosage to 3 mg/kg once weekly. ( 2.2 ) For patients with continued suboptimal clinical response, further increase the dosage to 5 mg/kg once weekly. ( 2.2 ) Pediatric and Adult Patients with LAL Deficiency: The recommended dosage is 1 mg/kg as an intravenous infusion once every other week. ( 2.2 ) For patients with a suboptimal clinical response, increase the dosage to 3 mg/kg once every other week. ( 2.2 ) See Full Prescribing Information for complete Dosage and Administration Information. Administration Instructions Infuse over at least 2 hours. ( 2.4 ) Consider further prolonging the infusion time for patients receiving dosages greater than 1 mg/kg or for those who have experienced a hypersensitivity reaction. ( 2.4 ) Consider a 1-hour infusion for the 1 mg/kg dose in patients who tolerate the infusion. ( 2.4 ) 2.1 Recommendations Prior to KANUMA Treatment Administration of KANUMA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.1) ].

Hypersensitivity to Eggs or Egg Products: Consider the risks and benefits of treatment in patients with known systemic hypersensitivity reactions to eggs or egg products. ( 5.2 ) 5.1 Hypersensitivity Reactions Including Anaphylaxis Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with enzyme replacement therapies, including KANUMA. These reactions in KANUMA-treated patients were based on application of Sampson criteria to identify signs/symptoms consistent with anaphylaxis. In clinical trials, 3 (infants) of 106 (3%) patients treated with KANUMA experienced signs and symptoms consistent with anaphylaxis. These patients experienced reactions during infusion with signs and symptoms including chest discomfort, conjunctival injection, dyspnea, generalized and itchy rash, hyperemia, swelling of eyelids, rhinorrhea, severe respiratory distress, tachycardia, tachypnea, and urticaria. In clinical trials, 21 of 106 (20%) KANUMA-treated patients, including 9 of 14 (64%) infants and 12 of 92 (13%) pediatric patients who were 4 years and older and adults, experienced signs and symptoms either consistent with or that may be related to a hypersensitivity reaction. Signs and symptoms of hypersensitivity reactions, occurring in two or more patients, included abdominal pain, agitation, fever, chills, diarrhea, eczema, edema, hypertension, irritability, laryngeal edema, nausea, pallor, pruritus, rash, and vomiting. The majority of reactions occurred during or within 4 hours of the completion of the infusion.

The most common adverse reactions are: Infants with Rapidly Progressive LAL Deficiency Presenting within the First 6 Months of Life (≥30%): diarrhea, vomiting, fever, rhinitis, anemia, cough, nasopharyngitis, and urticaria. ( 6.1 ) Pediatric and Adult Patients with LAL Deficiency (≥8%): headache, fever, oropharyngeal pain, nasopharyngitis, asthenia, constipation, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alexion at 1-844-259-6783 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In clinical trials, a total of 106 patients received treatment with KANUMA. The data described below reflect exposure to KANUMA in 75 patients who received KANUMA at dosages up to 3 mg/kg once weekly in clinical trials: Nine patients (5 males, 4 females) who had growth failure or other evidence of rapidly progressive LAL deficiency presenting within the first 6 months of life received KANUMA for up to 165 weeks (median 60 weeks) at escalating doses ranging between 0.35 mg/kg and 5 mg/kg once weekly [see Clinical Studies (14.1) ] . 66 pediatric and adult patients with LAL deficiency aged 4 to 58 years (33 males, 33 females) received KANUMA 1 mg/kg every other week for up to 36 weeks.

8.1 Pregnancy Risk Summary Available data with KANUMA use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Animal reproductive studies conducted with sebelipase alfa showed no evidence of embryolethality, fetotoxicity, teratogenicity, or abnormal early embryonic development at dosages up to 164 and 526 times the human dosage of 1 mg/kg every other week (based on AUC) in rats and rabbits, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Animal Data Sebelipase alfa administered during the period of organogenesis to rats (on gestation days 6, 9, 12, 15 and 17) and rabbits (on gestation days 7, 10, 13, 16 and 19) at intravenous doses up to 60 and 50 mg/kg, respectively, (approximately 164 and 526 times the human AUC of 1387 ng.h/mL at 1 mg/kg dose administered once every other week, respectively) did not cause any adverse effects on embryofetal development.

Metabolism

The pharmacokinetic profile of sebelipase alfa was nonlinear with a greater than dose-proportional increase in exposure between 1 and 3 mg/kg based on non-compartmental analysis of data from 26 adults. No accumulation was observed following once weekly or once every other week dosing.

• Dec 8, 2015BLABLA125561Alexion Pharm

1. 1Pyrexia599.2%
2. 2Off Label Use487.5%
3. 3Diarrhoea467.2%
4. 4Vomiting426.5%
5. 5Drug Ineffective274.2%
6. 6Headache264.0%
7. 7Low Density Lipoprotein Increased233.6%
8. 8Malaise223.4%
9. 9Blood Cholesterol Increased193.0%
10. 10Fatigue193.0%
11. 11Infusion Related Reaction193.0%
12. 12Weight Increased182.8%
13. 13Cough172.6%
14. 14Death172.6%
15. 15Nausea172.6%

The 9 most recently updated of 9 ClinicalTrials.gov registrations naming Sebelipase Alfa as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)
  Recruiting · Phase 1 · Interventional · 10 enrolled · University of California, San Francisco
  NCT04532047updated 2026-03-17
• Acid Lipase Replacement Investigating Safety and Efficacy (ARISE) in Participants With Lysosomal Acid Lipase Deficiency
  Completed · Phase 3 · Interventional · 66 enrolled · Alexion Pharmaceuticals, Inc.
  NCT01757184updated 2020-12-29
• Safety and Efficacy Study of Sebelipase Alfa in Participants With Lysosomal Acid Lipase Deficiency
  Completed · Phase 2 · Interventional · 31 enrolled · Alexion Pharmaceuticals, Inc.
  NCT02112994updated 2019-12-04
• Clinical Study In Infants With Rapidly Progressive Lysosomal Acid Lipase Deficiency
  Terminated · Phase 2 · Interventional · 10 enrolled · Alexion Pharmaceuticals, Inc.
  NCT02193867updated 2019-11-18
• Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Sebelipase Alfa in Children With Growth Failure Due to Lysosomal Acid Lipase Deficiency
  Completed · Phase 2 · Phase 3 · Interventional · 9 enrolled · Alexion Pharmaceuticals, Inc.
  NCT01371825updated 2019-01-30
• Safety, Tolerability and Pharmacokinetics of SBC-102 (Sebelipase Alfa) in Adult Participants With Lysosomal Acid Lipase Deficiency
  Completed · Phase 1 · Phase 2 · Interventional · 9 enrolled · Alexion Pharmaceuticals, Inc.
  NCT01307098updated 2018-12-11
• Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of SBC-102 (Sebelipase Alfa) in Adult Subjects With Lysosomal Acid Lipase Deficiency
  Completed · Phase 2 · Interventional · 8 enrolled · Alexion Pharmaceuticals, Inc.
  NCT01488097updated 2018-07-20
• Screening for Lysosomal Acid Lipase Deficiency
  Terminated · Observational · 22 enrolled · Alexion Pharmaceuticals, Inc.
  NCT02926872updated 2017-06-16
• An Expanded Access Protocol for Sebelipase Alfa for Patients With Lysosomal Acid Lipase Deficiency
  No longer available · Expanded access · Alexion Pharmaceuticals, Inc.
  NCT02376751updated 2016-06-08

Frequently asked questions

How does Sebelipase Alfa work?

LAL deficiency is an autosomal recessive lysosomal storage disorder characterized by a genetic defect resulting in a marked decrease or loss in activity of the lysosomal acid lipase (LAL) enzyme. The primary site of action of the LAL enzyme is the lysosome, where the enzyme normally causes the breakdown of lipid particles, including LDL-c and triglycerides.

What is Sebelipase Alfa used for?

According to FDA labeling, Sebelipase Alfa carries indications including: KANUMA ® is indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency. KANUMA ® is a hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Sebelipase Alfa?

Sebelipase Alfa is classified as Enzymes, Hydrolytic Lysosomal Cholesteryl Ester-specific Enzyme, Hydrolytic Lysosomal Triacylglycerol-specific Enzyme, Receptor Interactions, Increased Cholesterol Synthesis.

What are the brand names for Sebelipase Alfa?

Sebelipase Alfa is marketed under brand names including Kanuma.

What are the contraindications for Sebelipase Alfa?

Sebelipase Alfa labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.