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Sebelipase Alfa

FDA Drug Information • Also known as: Kanuma

Brand Names
Kanuma
Drug Class
Hydrolytic Lysosomal Cholesteryl Ester-specific Enzyme [EPC], Hydrolytic Lysosomal Triacylglycerol-specific Enzyme [EPC]
Route
INTRAVENOUS
Dosage Form
INJECTION, SOLUTION, CONCENTRATE
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate KANUMA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue KANUMA 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 [see Warnings and Precautions (5.1) ]. WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS See full prescribing information for complete boxed warning. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. ( 5.1 ) Initiate KANUMA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation. ( 5.1 ) If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue KANUMA and immediately initiate appropriate medical treatment, including use of epinephrine. ( 5.1 )

Description

11 DESCRIPTION Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL) that is a lysosomal glycoprotein enzyme produced by recombinant DNA technology in the egg white of eggs laid by genetically engineered chickens. Purified sebelipase alfa is a monomeric glycoprotein containing 6 N-linked glycosylation sites and has a molecular mass of approximately 55 kDa. The amino acid sequence for sebelipase alfa is the same as the amino acid sequence for human LAL. The specific activity of sebelipase alfa is 195 to 345 units/mg. One unit is the amount of enzyme activity that catalyzes the hydrolysis of 1 micromole of the synthetic substrate 4-methylumbelliferyl oleate per minute at 37°C under specified assay conditions. KANUMA (sebelipase alfa) injection is supplied as a sterile, preservative-free, non-pyrogenic clear to slightly opalescent, colorless to slightly colored aqueous solution in single-dose vials for intravenous infusion. Each vial contains sebelipase alfa 20 mg/10 mL. Each mL of solution contains sebelipase alfa (2 mg), citric acid monohydrate (1.57 mg), Human Serum Albumin (10 mg), and trisodium citrate dihydrate (13.7 mg) at pH 5.9.

What Is Sebelipase Alfa Used For?

1 INDICATIONS AND USAGE 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. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION 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) ]. Initiate KANUMA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1) ]. 2.2 Recommended Dosage Infants with Rapidly Progressive LAL Deficiency Presenting within the First 6 Months of Life: The recommended starting dosage is 1 mg/kg administered as an intravenous infusion once weekly. For patients with a suboptimal clinical response, increase the dosage to 3 mg/kg once weekly. For patients with continued suboptimal clinical response on the 3 mg/kg once weekly dosage, further increase the dosage to 5 mg/kg once weekly. A suboptimal clinical response is defined as any of the following: poor growth, deteriorating biochemical markers, or persistent or worsening organomegaly. Pediatric and Adult Patients with LAL Deficiency: The recommended dosage is 1 mg/kg administered as an intravenous infusion once every other week. For patients with a suboptimal clinical response, increase the dosage to 3 mg/kg once every other week. A suboptimal clinical response is defined as any of the following: poor growth, deteriorating biochemical markers [e.g., alanine aminotransferase (ALT), aspartate aminotransferase (AST)], and/or parameters of lipid metabolism [e.g., low-density lipoprotein cholesterol (LDL-c), triglycerides (TG)]. 2.3 Preparation Instructions KANUMA is for intravenous infusion only. Prepare KANUMA using the following steps. Determine the number of...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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. Table 2 summarizes the most common adverse reactions occurring in >30% of patients with rapidly progressive LAL deficiency presenting within the first 6 months of life receiving KANUMA in Study 1. Table 2: Adverse Reactions in ≥30% of Infants with Rapidly Progressive LAL Deficiency Presenting within the First 6 Months of Life Receiving KANUMA Adverse Reactions KANUMA N=9 n (%) Diarrhea 6 (67) Vomiting 6 (67) Fever 5 (56) Rhinitis 5 (56) Anemia 4 (44) Cough 3 (33) Nasopharyngitis 3 (33) Urticaria 3 (33) Other less common adverse reactions reported in patients with rapidly progressive disease presenting within the first 6 months of life who received KANUMA included hypotonia, decreased oxygen saturation, retching, sneezing, and tachycardia. For infant patients within Study 1 and Study 3 (n = 19), the following additional adverse reactions were reported in ≥ 30% of infants who received KANUMA since the time of marketing authorization, including patients who received an escalated dose to 5 mg/kg qw: hypersensitivity, respiratory distress, and tachycardia. Table 3 summarizes the most common adverse reactions that occurred in ≥8% of pediatric and adult patients with LAL deficiency receiving KANUMA in Study 2. Table 3: Adverse Reactions in ≥8% of Pediatric and Adult Patients with LAL Deficiency Receiving KANUMA Adverse Reactions KANUMA N = 36 Placebo N = 30 n (%) n (%) Headache 10 (28) 6 (20) Fever 9 (25) 7 (23) Oropharyngeal pain 6 (17) 1 (3) Nasopharyngitis 4 (11) 3 (10) Asthenia 3 (8) 1 (3) Constipation 3 (8) 1 (3) Nausea 3 (8) 2 (7) Other less common adverse reactions reported in pediatric and adult patients who received KANUMA included anxiety and chest discomfort. For pediatric and adult patients (n = 106), the following additional adverse reactions were reported in ≥ 8% of pediatric and adult patients who received KANUMA since the time of marketing authorization, including patients who received an escalated dose to 3 mg/kg qw: hypersensitivity, diarrhea, abdominal pain, and dizziness. Hyperlipidemia Increases in circulating LDL-cholesterol (LDL-c) and triglycerides above pre-treatment values were observed in 29 of 36 (81%) and 21 of 36 (58%) patients, respectively, at 2 and 4 weeks following initiation of KANUMA [see Clinical Pharmacology (12.2) ] . The maximum mean percentage increase was 18% for LDL-c at Week 2 and 5% for triglycerides at Week 4. 6.2 Immunogenicity As with all therapeutic proteins, there is potential for...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

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. A pre- and post-natal development study in rats showed no evidence of adverse effects on pre- and postnatal development at intravenous doses (administered on gestation days 6, 9, 12, 15, 18, and 20 and days 4, 7, 10, 14, and 17 postpartum) of sebelipase alfa up to 60 mg/kg/day (approximately 164 times the human AUC of 1387 ng.h/mL at 1 mg/kg dose administered once every other week).

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING KANUMA (sebelipase alfa) injection is a preservative-free, clear to slightly opalescent, colorless to slightly colored, nonpyrogenic solution supplied as 20 mg/10 mL (2 mg/mL) in single-dose, glass vials. NDC 25682-007-01: 20 mg/10 mL vial Store KANUMA refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not shake or freeze the vials.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.