Kanuma (Sebelipase Alfa)
Enzyme replacement therapy for lysosomal acid lipase deficiency (LAL-D)
Kanuma (sebelipase alfa) is the first and only enzyme replacement therapy approved for the treatment of lysosomal acid lipase deficiency (LAL-D), a rare genetic condition that causes harmful accumulation of fats in the liver, spleen, and blood vessels. It is approved for use in patients of all ages, including newborns with the severe infantile-onset form (Wolman disease). Kanuma is administered by intravenous infusion and is intended for lifelong use under specialist supervision.
Quick Facts
Key Takeaways
- Kanuma is the only approved enzyme replacement therapy for lysosomal acid lipase deficiency (LAL-D), a rare genetic disease affecting approximately 1 in 40,000 to 1 in 300,000 people worldwide.
- It is given as an intravenous infusion every other week in children and adults (1 mg/kg), or weekly in infants under 6 months with rapidly progressive disease (1–3 mg/kg).
- Infusion-related reactions, including potentially life-threatening anaphylaxis, are possible. Patients are monitored closely during and after each infusion.
- Kanuma may contain egg proteins. Patients with known egg allergy must discuss this with their healthcare provider before starting treatment.
- Treatment is lifelong and should be started as early as possible. Clinical trials have demonstrated significant improvements in liver function, blood lipids, and survival in infants with severe disease.
What Is Kanuma and What Is It Used For?
Kanuma contains the active substance sebelipase alfa, a recombinant (bioengineered) form of the naturally occurring enzyme lysosomal acid lipase (LAL). This enzyme is normally present in the lysosomes — specialised compartments within every cell of the body — where it plays a critical role in breaking down cholesteryl esters and triglycerides into free cholesterol and free fatty acids that the body can then use or excrete.
In patients with LAL deficiency, mutations in the LIPA gene lead to absent or severely reduced LAL enzyme activity. Without sufficient LAL, these lipids cannot be properly metabolised and instead accumulate progressively within the lysosomes of cells throughout the body, particularly in the liver, spleen, intestines, and blood vessel walls. This lipid accumulation drives a cascade of harmful effects, including liver damage (hepatomegaly, fibrosis, and eventually cirrhosis), splenomegaly, elevated blood cholesterol and triglyceride levels, and accelerated atherosclerosis.
LAL deficiency presents as a spectrum of disease severity. The most severe form, historically known as Wolman disease, manifests in the first weeks of life with failure to thrive, malabsorption, hepatosplenomegaly, and adrenal calcification. Without treatment, Wolman disease is typically fatal within the first year of life. The later-onset form, previously called cholesteryl ester storage disease (CESD), presents more variably, often in childhood or adulthood, with hepatomegaly, elevated liver enzymes, dyslipidaemia (high LDL cholesterol and triglycerides, low HDL cholesterol), and progressive liver disease that can lead to liver failure.
How Kanuma Works
Kanuma works by providing the body with a functional copy of the LAL enzyme that patients with LAL deficiency cannot produce in adequate quantities on their own. After intravenous infusion, sebelipase alfa is taken up by cells throughout the body via mannose-6-phosphate receptors on cell surfaces and is delivered to the lysosomes, where it catalyses the hydrolysis of accumulated cholesteryl esters and triglycerides.
By restoring LAL enzyme activity within the lysosomes, Kanuma reduces the pathological lipid accumulation that drives the clinical manifestations of LAL deficiency. Clinical studies have demonstrated that treatment with Kanuma leads to significant reductions in hepatic fat content, normalisation of liver transaminase levels (ALT and AST), improvements in blood lipid profiles (reduction in LDL cholesterol and triglycerides, increase in HDL cholesterol), and in infants with severe disease, marked improvements in weight gain and survival.
The ARISE trial, a pivotal phase 3 randomised, double-blind, placebo-controlled study in children and adults with LAL deficiency, demonstrated that sebelipase alfa significantly improved multiple disease-related parameters compared with placebo, including normalisation of ALT levels, reduction in LDL cholesterol, decrease in hepatic fat content, and improvement in HDL cholesterol. In the separate open-label study in infants with rapidly progressive disease, treatment with sebelipase alfa dramatically improved survival compared with historical outcomes for untreated Wolman disease.
What Should You Know Before Receiving Kanuma?
Contraindications
Kanuma must not be administered if you or your child have experienced a life-threatening hypersensitivity reaction (anaphylaxis) to sebelipase alfa that cannot be adequately managed when the medicine is given again. Additionally, Kanuma should not be used in patients with a known allergy to any of the excipients listed in the product formulation, including patients with severe egg allergy where the risk of anaphylaxis outweighs the potential benefit of treatment.
Kanuma may contain trace amounts of egg protein from the manufacturing process. If you or your child have an egg allergy or have previously experienced allergic reactions to eggs, you must inform your doctor before starting treatment. The decision to initiate or continue Kanuma therapy in egg-allergic patients must be made carefully by the treating specialist.
Warnings and Precautions
Infusion-related reactions are among the most significant risks associated with Kanuma therapy. These reactions can occur during or within hours after the infusion and may range from mild symptoms (such as flushing, fever, or nausea) to severe and potentially life-threatening anaphylaxis. In clinical trials, anaphylaxis was reported as very common in infants under 6 months and common in older children and adults.
During the first infusion of Kanuma, you or your child should be observed by healthcare professionals for at least one hour after the infusion to monitor for any signs of an infusion-related reaction. If such a reaction occurs, your doctor will initiate appropriate medical treatment immediately. In some cases, additional medications may be given before future infusions to reduce the risk of recurrence, including antihistamines, antipyretics (fever-reducing medicines), and corticosteroids.
If an infusion-related reaction is severe, the infusion may be slowed or temporarily stopped. In cases of life-threatening anaphylaxis, the infusion will be discontinued and emergency medical treatment will be administered. The decision to re-challenge a patient who has experienced severe anaphylaxis must be made carefully by the treating specialist.
Development of anti-drug antibodies (immune proteins against the medicine) can occur during treatment with Kanuma. If you notice that the treatment appears to be becoming less effective over time, inform your doctor, as this may indicate the development of neutralising antibodies that could reduce the clinical response to sebelipase alfa.
Pregnancy and Breastfeeding
There are no adequate clinical data on the use of sebelipase alfa in pregnant women. As a precautionary measure, Kanuma should not be administered during pregnancy unless clearly necessary and the potential benefit justifies the potential risk to the foetus. Women of childbearing potential should discuss family planning with their specialist.
It is not known whether sebelipase alfa is excreted in human breast milk. If you are breastfeeding or planning to breastfeed, discuss the options with your doctor. Together, you can weigh the benefits of breastfeeding for the infant against the benefits of continuing Kanuma treatment for you.
Driving and Operating Machinery
Kanuma may have a minor effect on the ability to drive or operate machinery. Among the reported side effects of sebelipase alfa is dizziness, which could potentially impair your ability to drive or use machines safely. If you experience dizziness after receiving an infusion, you should wait until the symptom resolves before driving or operating machinery.
Sodium Content
When diluted with 0.9% sodium chloride solution for intravenous infusion, the recommended dose of Kanuma contains approximately 33 mg of sodium (the main component of table salt) per dose. This is equivalent to approximately 1.7% of the recommended maximum daily sodium intake for an adult. Inform your doctor if you or your child are on a controlled sodium (salt) diet.
How Does Kanuma Interact with Other Drugs?
Sebelipase alfa is a recombinant protein that functions within the lysosomal compartment of cells. Unlike small-molecule drugs, it does not undergo hepatic metabolism via cytochrome P450 enzymes and is not known to inhibit or induce drug-metabolising enzymes or transporters. As a result, direct pharmacokinetic drug interactions are considered unlikely.
Nevertheless, patients with LAL deficiency often have significant dyslipidaemia and may be receiving concomitant lipid-lowering therapy such as statins, ezetimibe, or other agents. There is no evidence from clinical trials that Kanuma interacts adversely with these medications. In the ARISE trial, many patients continued their background lipid-lowering therapy while receiving sebelipase alfa, and no drug-drug interactions were identified.
It is important to tell your doctor or nurse about all medicines you or your child are currently taking, have recently taken, or might take. This includes prescription medicines, over-the-counter medications, vitamins, and herbal supplements. Although significant interactions are not expected, your healthcare team should have a complete picture of all treatments to ensure optimal management of your condition.
Patients who experience infusion-related reactions may be given pre-treatment medications including antihistamines (e.g., diphenhydramine, cetirizine), antipyretics (e.g., paracetamol/acetaminophen), and corticosteroids (e.g., hydrocortisone, methylprednisolone) before each infusion. These are used to help prevent or reduce the severity of infusion reactions and are not considered drug interactions.
| Medication Class | Examples | Clinical Consideration |
|---|---|---|
| Statins (HMG-CoA reductase inhibitors) | Atorvastatin, rosuvastatin, simvastatin | May be continued concurrently. Lipid parameters should be monitored as Kanuma may improve lipid profiles |
| Cholesterol absorption inhibitors | Ezetimibe | May be used alongside Kanuma. Dose adjustment may be considered as lipid levels improve |
| Antihistamines | Diphenhydramine, cetirizine | Commonly used as pre-medication to prevent infusion-related reactions |
| Corticosteroids | Hydrocortisone, methylprednisolone | May be used as pre-medication for patients with history of infusion reactions |
| Antipyretics | Paracetamol (acetaminophen), ibuprofen | Commonly used as pre-medication to prevent fever during infusion |
What Is the Correct Dosage of Kanuma?
Kanuma is administered exclusively by intravenous infusion in a clinical setting by trained healthcare professionals. The dose is calculated based on the patient's body weight, and the infusion is typically delivered over 1 to 2 hours. Treatment should be initiated as early as possible following diagnosis and is intended for long-term, indefinite use.
Infants (Under 6 Months)
Infantile-Onset LAL Deficiency (Wolman Disease)
For infants presenting with signs and symptoms of rapidly progressive LAL deficiency in the first 6 months of life, the recommended starting dose is 1 mg/kg or 3 mg/kg administered as an intravenous infusion once weekly. The starting dose is determined by the treating specialist based on the severity and pace of disease progression.
Dose escalation up to 5 mg/kg once weekly may be considered in patients who do not achieve an optimal clinical response at 3 mg/kg. The dose should be adjusted based on ongoing assessment of clinical markers, including growth parameters, hepatic function, haematological indices, and overall clinical status.
Children and Adults
Later-Onset LAL Deficiency (CESD)
For children (aged 6 months and older) and adults, the recommended dose is 1 mg/kg administered as an intravenous infusion once every two weeks (every other week). Dose adjustments may be considered based on individual clinical response, including liver transaminase levels, blood lipid profiles, and hepatic fat content.
Infusion Administration
Each infusion is typically delivered over approximately 1 to 2 hours. The infusion rate may be adjusted (slowed or temporarily paused) if an infusion-related reaction occurs. You or your child may be monitored by healthcare staff for an additional hour after the infusion, particularly during the initial infusions, to ensure no delayed reactions occur.
The concentrate must be diluted with 0.9% sodium chloride solution before administration. The diluted solution should be administered using a low-protein-binding infusion set with a low-protein-binding 0.2 µm in-line filter with a surface area greater than 4.5 cm² when available, to prevent filter occlusion.
| Body Weight (kg) | 1 mg/kg Dose (ml) | 3 mg/kg Dose (ml) | 5 mg/kg Dose (ml) |
|---|---|---|---|
| 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 |
Note: The 5 mg/kg dose is reserved for infants with LAL deficiency onset in the first 6 months of life who do not achieve optimal clinical response at the 3 mg/kg dose. Infusion volumes should achieve a final sebelipase alfa concentration of 0.1–1.5 mg/ml.
Missed Dose
If an infusion session is missed, contact your healthcare provider as soon as possible to reschedule. It is important to maintain the regular infusion schedule to ensure continuous enzyme replacement and prevent re-accumulation of lipids. Your doctor will advise on the best time to resume treatment.
Overdose
There is limited experience with overdose of Kanuma. In the event that a higher dose than prescribed is administered, the patient should be monitored closely for any signs of adverse effects, particularly infusion-related reactions. Treatment is supportive and symptomatic. As Kanuma is administered under medical supervision, the risk of accidental overdose is low.
What Are the Side Effects of Kanuma?
Like all medicines, Kanuma can cause side effects, although not everyone experiences them. The most significant side effects are infusion-related reactions, which can occur during the infusion or in the hours following administration. These reactions are caused by the immune system responding to the infused protein and can range from mild and transient to severe and potentially life-threatening.
The most serious potential side effect is anaphylaxis (a severe allergic reaction), which requires immediate medical attention. Signs of anaphylaxis include difficulty breathing, rapid breathing, rapid heartbeat, chest tightness, swelling of the eyelids, red eyes, runny nose, flushing, hives, itching, pallor, wheezing, and low blood oxygen levels. If you or your child experience any of these symptoms, seek medical attention immediately.
Anti-drug antibodies (immune proteins directed against sebelipase alfa) may develop during treatment. Your doctor will monitor for signs that the treatment may be becoming less effective, which could indicate the development of neutralising antibodies.
Side Effects in Infants (1 to 6 Months)
Very Common
May affect more than 1 in 10 infants
- Hypersensitivity reactions (irritability, agitation, vomiting, hives, eczema, itching, pallor)
- Anaphylactic reactions (severe allergic reactions)
- Swollen eyelids
- Rapid heartbeat (tachycardia)
- Difficulty breathing (respiratory distress)
- Diarrhoea and vomiting
- Rash and raised rash (urticaria)
- Fever (pyrexia)
- Decreased blood oxygen levels (oxygen desaturation)
- Elevated blood pressure (hypertension)
- Rapid breathing (tachypnoea)
- Development of anti-drug antibodies
Side Effects in Children, Adolescents, and Adults
Very Common
May affect more than 1 in 10 people
- Hypersensitivity reactions (chills, eczema, laryngeal oedema, nausea, itching, hives)
- Dizziness
- Abdominal pain
- Diarrhoea
- Fatigue
- Fever (pyrexia)
Common
May affect up to 1 in 10 people
- Anaphylactic reactions (severe allergic reactions)
- Rapid heartbeat (tachycardia)
- Flushing (skin reddening)
- Low blood pressure (hypotension)
- Shortness of breath (dyspnoea)
- Abdominal distension (bloating)
- Skin rash and erythema (red, swollen skin)
- Chest discomfort
- Infusion site reactions
The frequency, type, and severity of side effects in children are similar to those observed in adults. If you or your child experience any side effects that concern you, or if symptoms worsen or persist, contact your healthcare provider promptly.
It is important to report suspected side effects after a medicine has been authorised. This allows continuous monitoring of the medicine's benefit-risk balance. Healthcare professionals and patients are encouraged to report suspected adverse reactions to their national pharmacovigilance authority (e.g., the FDA MedWatch programme in the United States, the Yellow Card Scheme in the United Kingdom, or the EudraVigilance system in the European Union).
How Should You Store Kanuma?
Keep this medicine out of the sight and reach of children. Do not use Kanuma after the expiry date stated on the label and carton after “EXP”. The expiry date refers to the last day of that month.
- Unopened vials: Store in a refrigerator at 2°C to 8°C. Do not freeze. Do not shake. Store in the original packaging to protect from light.
- Diluted solution (if not used immediately): May be stored at 2°C to 8°C for up to 24 hours, or at below 25°C for up to 12 hours.
- Important: Each vial is for single use only. Any unused portion must be discarded.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help to protect the environment.
What Does Kanuma Contain?
The active substance is sebelipase alfa. Each millilitre of concentrate contains 2 mg of sebelipase alfa. Each single-use vial contains 20 mg of sebelipase alfa in 10 ml of concentrate.
The other ingredients (excipients) are:
- Sodium citrate — acts as a buffer to maintain the correct pH of the solution
- Citric acid monohydrate — acts as a buffer
- Human serum albumin — acts as a stabiliser to protect the active protein
- Water for injections — the solvent
Appearance and Packaging
Kanuma is supplied as a concentrate for solution for infusion (sterile concentrate). It is a clear to slightly opalescent, colourless to slightly coloured (yellowish) solution. Some slight flocculation (e.g., thin, translucent fibres) may be present in the concentrate, which is acceptable for use. Do not use the concentrate if it is cloudy or contains foreign particles.
Pack size: 1 vial containing 10 ml of concentrate.
The marketing authorisation holder is Alexion Europe SAS, 103-105 rue Anatole France, 92300 Levallois-Perret, France. Kanuma is part of the AstraZeneca Rare Disease portfolio following the acquisition of Alexion Pharmaceuticals.
Frequently Asked Questions About Kanuma
Kanuma (sebelipase alfa) is used to treat patients of all ages with lysosomal acid lipase deficiency (LAL-D), also known as Wolman disease in its severe infantile form or cholesteryl ester storage disease (CESD) in later-onset presentations. It is an enzyme replacement therapy that replaces the missing or deficient LAL enzyme to reduce fat accumulation in the liver and other organs, improve liver function, and normalise blood lipid levels.
Kanuma is administered as an intravenous (IV) infusion in a healthcare setting by trained professionals. For infants under 6 months with rapidly progressive disease, the recommended starting dose is 1 mg/kg or 3 mg/kg once weekly. For children and adults, the recommended dose is 1 mg/kg every other week. Each infusion takes approximately 1 to 2 hours, and patients are typically monitored for an additional hour afterwards.
The most common side effects are infusion-related reactions, which may include fever, chills, nausea, vomiting, abdominal pain, diarrhoea, hives, rash, dizziness, rapid heartbeat, and fatigue. In infants, hypersensitivity reactions including anaphylaxis are very common. Patients are closely monitored during and after each infusion for signs of allergic reactions.
Kanuma may contain trace amounts of egg proteins from the manufacturing process. Patients with a known egg allergy or previous allergic reactions to eggs must inform their healthcare provider before starting treatment. The risk of hypersensitivity reactions may be higher in these individuals, and the decision to initiate treatment must be made carefully by the treating specialist after weighing the benefits and risks.
Yes, Kanuma is intended for long-term, indefinite use. Since it replaces an enzyme that the body cannot produce sufficiently on its own due to a genetic mutation, discontinuing treatment would allow the re-accumulation of lipids in tissues and the return of disease symptoms. Treatment should be started as early as possible and continued under regular specialist supervision, with dose adjustments as needed.
LAL deficiency is a very rare genetic disorder with an estimated prevalence of approximately 1 in 40,000 to 1 in 300,000 people, depending on the population studied and the severity of the disease. The severe infantile-onset form (Wolman disease) is rarer, with an estimated incidence of approximately 1 in 100,000 to 1 in 500,000 live births. The condition is inherited in an autosomal recessive pattern, meaning both parents must carry a mutation in the LIPA gene.
References
- European Medicines Agency (EMA). Kanuma (sebelipase alfa) — European Public Assessment Report (EPAR). First published 2015, last updated 2023. Available at: ema.europa.eu/en/medicines/human/EPAR/kanuma
- Burton BK, Balwani M, Feillet F, et al. A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency (ARISE study). N Engl J Med. 2015;373(11):1010-1020. doi:10.1056/NEJMoa1501365
- Jones SA, Valayannopoulos V, Schneider E, et al. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genet Med. 2016;18(5):452-458. doi:10.1038/gim.2015.108
- U.S. Food and Drug Administration (FDA). KANUMA (sebelipase alfa) Prescribing Information. Revised 2023. Available at: FDA Prescribing Information
- Bernstein DL, Hülková H, Levin MV, et al. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013;58(6):1230-1243. doi:10.1016/j.jhep.2013.02.014
- World Health Organization (WHO). Rare Diseases — International collaboration for access to orphan medicines. Available at: who.int
- National Institute for Health and Care Excellence (NICE). Sebelipase alfa for treating lysosomal acid lipase deficiency. Highly Specialised Technologies guidance [HST5]. Published 2017. Available at: nice.org.uk/guidance/hst5
Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, which includes board-certified specialists in metabolic diseases, clinical pharmacology, paediatric medicine, and hepatology. Our team follows international guidelines from the EMA, FDA, WHO, and NICE to ensure all information is accurate, up-to-date, and evidence-based.
All content is based on peer-reviewed clinical trials, approved product information (SmPC/EPAR), and international treatment guidelines. Evidence level: 1A (systematic reviews and randomised controlled trials).
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