sebelipase alfa

Action and Spectrum

Mechanism of action 

The mechanism of action of sebelipase alfa is by replacing the deficient or non-functioning LAL enzyme in the body, allowing it to break down fatty materials (lipids) such as cholesteryl esters and triglycerides. By breaking down these lipids, it prevents the accumulation of lipids in the organs and tissues, thus reducing the symptoms of LALD 

Spectrum 

It can reduce the accumulation of lipids in various organs and tissues, such as the liver, spleen, and blood vessels. It can also improve symptoms such as liver dysfunction, splenomegaly, and atherosclerosis. It is also shown to improve the growth and development of pediatric patients with LALD. It is usually administered by intravenous injection once a week, and the dosage is based on the patient’s weight and LAL activity levels 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

<6 months age: 

vomiting 

rhinitis 

cough 

urticaria 

diarrhea 

fever 

anemia 

nasopharyngitis 

Adults and pediatrics 

Fever  

Nasopharyngitis 

Headache 

Oropharyngeal pain 

1-10% 

Adults and pediatrics 

Constipation 

Asthenia 

Nausea 

Black Box Warning

Contraindication / Caution

Contraindications 

None 

Caution 

Some precautions to be taken while using sebelipase alfa include: 

• It should be used with caution in patients with a history of anaphylaxis or severe allergic reactions to the drug or its excipients. 
• It should not be administered to patients with active or latent infections or those with a high risk of infections. 
• It should be used cautiously in patients with liver or renal impairment, as the drug may exacerbate these conditions. 
• Patients should be monitored for an increase in liver enzymes, lipase, and amylase, during treatment with sebelipase alfa. 
• It should be used with caution in pregnant or breastfeeding women, as there is limited data on drug safety in these populations. 
• It should be used with caution in patients receiving other medications that may affect the liver, such as statins, as the combined use of these drugs may increase the risk of liver dysfunction. 
• Patients should be advised to avoid close contact with individuals who have known infections or have recently been vaccinated, as the risk of infection may be increased in LALD patients receiving sebelipase alfa 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology 

It is a recombinant form of the human lysosomal acid lipase (LAL) enzyme that is used to treat Lysosomal Acid Lipase Deficiency (LALD). LALD is an inherited disorder caused by a genetic defect that results in a marked decrease or loss of activity of the LAL enzyme. The LAL enzyme is responsible for breaking down lipids in the lysosome. A deficiency in LAL enzyme activity leads to the accumulation of lipids in various organs and tissues, including the liver, spleen, intestine, and walls of blood vessels. 

The accumulation of lipids in the liver can lead to increased liver fat content and the progression of liver disease, such as fibrosis and cirrhosis. Lipid accumulation in the intestinal wall can cause malabsorption and growth failure. Patients with LALD may also have dyslipidemia, characterized by elevated levels of LDL-c and triglycerides and low levels of HDL-c. Sebelipase alfa replaces the deficient or non-functioning LAL enzyme in the body, allowing it to break down fatty materials (lipids) such as cholesteryl esters and triglycerides. Breaking down these lipids prevents lipids accumulation in the organs and tissues, thus reducing the symptoms of LALD. 

Pharmacodynamics 

It is a replacement enzyme therapy for patients with Lysosomal Acid Lipase Deficiency (LALD) caused by a genetic defect that results in a marked decrease or loss of activity of the LAL enzyme. As it is produced using recombinant DNA technology in the eggs of genetically engineered chickens, it should be used with caution in patients with a known history of egg allergy. 

Patients with a known history of egg allergy may have an increased risk of an allergic reaction to sebelipase alfa. It is essential to inform the healthcare provider if the patient has a history of egg allergy before starting treatment with sebelipase alfa. 

Pharmacokinetics 

Absorption: 

It is administered by intravenous (IV) injection, so there is no need for absorption as it directly eners the bloodstream. 

Distribution:  

After IV administration, sebelipase alfa is rapidly distributed throughout the body, with a high volume of distribution of approximately 8-17 L. The drug is not bound to plasma proteins and the steady state concentrations can be reached within 4-8 weeks after initiation of treatment. 

Metabolism:  

It is not metabolized in the body and is not subject to first-pass metabolism. 

Elimination/Excretion: 

 It is excreted mainly by the kidneys, with a small fraction excreted in feces. The renal elimination is slow, with a mean renal clearance of approximately 0.1-0.2 mL/kg/week. The half-life of sebelipase alfa is 5-7 days 

Adminstartion

Administration 

Intravenous administration 

To administer an IV infusion using a low-protein binding infusion set with an in-line, low-protein binding 0.2-micron filter, infuse the medication over at least 2 hours. For patients receiving doses greater than 1 mg/kg or those who have experienced hypersensitivity reactions, consider prolonging the infusion time. A 1-hr infusion may be considered for patients receiving a 1 mg/kg dose who tolerate the infusion well. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sebelipase alfa 

Pronounced: [ SE-be-LYE-pase-AL-fa] 

Why do we use sebelipase alfa? 

It is a recombinant form of the human lysosomal acid lipase enzyme and it is used to treat lysosomal acid lipase deficiency (LAL-D)