olipudase alfa

Action and Spectrum

Actions and Spectrum: 

The action of olipudase alfa involves replacing the missing or deficient acid sphingomyelinase enzyme in patients with ASMD. It is a recombinant form of human acid sphingomyelinase produced through biotechnology.

When administered, olipudase alfa helps to break down sphingomyelin into ceramide and other products, reducing the accumulation of sphingomyelin in cells and tissues. 

By reducing the accumulation of sphingomyelin, olipudase alfa aims to alleviate the symptoms and slow the progression of ASMD, helping to improve the quality of life of affected individuals. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Adults 

Elevated transaminase levels (13%) 

Cough (31%) 

Diarrhea (15%) 

Hypotension (15%) 

Headache (54%) 

Ocular hyperemia (15%) 

Children 

Hypotension (13%) 

Vomiting (50%) 

Diarrhea (75%) 

Arthralgia (38%) 

Pyrexia (100%) 

Pruritus (25%) 

Cough (75%) 

Pharyngitis (25%) 

Elevated transaminase levels (13%) 

Nausea (38%) 

Rash (38%) 

Tachycardia (13%) 

Rhinitis (75%) 

Headache (50%) 

Fatigue (25%) 

Infusion site swelling (13%) 

Abdominal pain (63%) 

Hypersensitivity (13%) 

Anaphylactic reaction (13%) 

Pharyngeal swelling (13%) 

Urticaria (50%) 

C-reactive protein increased (13%) 

1-10% 

Adults 

Urticaria (8%) 

Myalgia (8%) 

Asthenia (8%) 

Throat irritation (8%) 

Erythema (8%) 

Dyspnea (8%) 

Papule (8%) 

C-reactive protein abnormal (8%) 

Pharyngitis (8%) 

Black Box Warning

Black Box Warning: 

• Hypersensitivity reactions with anaphylaxis: Certain individuals may experience hypersensitivity reactions to olipudase alfa. You should not use this medication if you have a known allergy to olipudase alfa or its components. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

None 

Caution 

• Hypersensitivity reactions: Certain individuals may experience hypersensitivity reactions to olipudase alfa. You should not use this medication if you have a known allergy to olipudase alfa or its components. 
• Risk of infusion-related reactions: olipudase alfa is administered intravenously (IV). As with any IV treatment, there may be a risk of infusion-related reactions, including allergic reactions, fever, chills, rash, and other symptoms. Healthcare providers should closely monitor patients during the infusion and take appropriate precautions to manage adverse reactions. 
• Development of antibodies: In some cases, patients treated with enzyme replacement therapies may develop antibodies against the therapeutic enzyme. These antibodies’ clinical significance and impact on treatment efficacy may vary from person to person. 
• Use during pregnancy and breastfeeding: The safety of olipudase alfa in pregnant or breastfeeding individuals has not been extensively studied.  
• Interaction with other medications: olipudase alfa’s interactions with other medications have not been extensively studied. Before starting olipudase alfa, it is crucial to inform the healthcare provider about all the drugs, supplements/herbal products you are taking to avoid potential drug interactions. 
• Use in specific patient populations: The safety and efficacy of olipudase alfa in specific patient populations, such as pediatric patients or those with severe hepatic or renal impairment, may require special consideration. Individualized dosing and careful monitoring may be necessary in these cases. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk: Not known. 

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 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: 

olipudase alfa is a recombinant form of human acid sphingomyelinase enzyme used to treat acid sphingomyelinase deficiency (ASMD), also known as Niemann-Pick disease type B. As an enzyme replacement therapy, olipudase alfa replaces the deficient or absent acid sphingomyelinase enzyme in patients with ASMD.

Upon intravenous administration, olipudase alfa helps to break down sphingomyelin into ceramide and other products, reducing the accumulation of sphingomyelin in cells and tissues. By reducing the buildup of sphingomyelin, olipudase alfa aims to alleviate the symptoms of ASMD and slow the progression of the disease. 

Pharmacodynamics: 

Mechanism of action: The action of olipudase alfa revolves around replacing the deficient or absent acid sphingomyelinase enzyme in patients with ASMD. 

ASMD is a rare genetic disorder characterized by a deficiency of the enzyme acid sphingomyelinase, as it is responsible for breaking down sphingomyelin in cells. Without a properly functioning acid sphingomyelinase enzyme, sphingomyelin accumulates within various organs and tissues, leading to the characteristic symptoms of the disease. 

olipudase alfa is a recombinant form of human acid sphingomyelinase enzyme produced through biotechnology. When administered intravenously, olipudase alfa circulates in the bloodstream and reaches affected tissues. Once in the lysosomes of cells, olipudase alfa replaces the missing or deficient acid sphingomyelinase enzyme. 

In the lysosomes, olipudase alfa catalyzes the breakdown of sphingomyelin into ceramide and other products. This enzymatic activity reduces the accumulation of sphingomyelin in cells and tissues, helping to restore the balance of sphingolipid metabolism. 

By reducing the buildup of sphingomyelin, olipudase alfa aims to alleviate the symptoms associated with ASMD and slow the progression of the disease, ultimately improving the quality of life for the affected individuals. 

Pharmacokinetics: 

Absorption 

olipudase alfa is administered intravenously, which means it is directly introduced into the bloodstream. As a result, absorption is instantaneous and complete since it bypasses the digestive system. 

Distribution 

Once in the bloodstream, olipudase alfa circulates throughout the body, distributing to various tissues. It is designed to target specific cells affected by acid sphingomyelinase deficiency, such as macrophages, which are cells involved in the breakdown and recycling of cellular waste. 

Metabolism 

olipudase alfa is a recombinant form of the human acid sphingomyelinase enzyme. The metabolism of olipudase alfa primarily involves the enzymatic breakdown of sphingomyelin, the substrate it acts upon, into ceramide and phosphocholine. This enzymatic process occurs in lysosomes, the cellular compartments responsible for waste degradation. 

Elimination and Excretion 

As an enzyme replacement therapy, olipudase alfa eventually undergoes degradation and clearance from the body. The breakdown products, such as ceramide and phosphocholine, are further processed and excreted from the body through normal physiological pathways. 

Adminstartion

Administration: 

Intravenous administration 

olipudase alfa is administered intravenously (IV). As an enzyme replacement therapy, it requires careful handling and administration by healthcare professionals in a clinical setting.  

• Preparation: Healthcare professionals will prepare the olipudase alfa solution following the manufacturer’s instructions. The medication is typically supplied as a sterile, clear, colorless liquid in single-use vials. 
• Intravenous Access: The patient will need an IV line established to administer olipudase alfa. This may involve inserting a small, flexible tube (catheter) into a vein, usually in the arm. 
• Infusion: The prepared olipudase alfa solution is then slowly infused into the patient’s vein over a specified period, as directed by the prescribing healthcare provider. The infusion time may vary depending on the patient’s condition and the healthcare provider’s recommendations. 
• Monitoring: Healthcare providers will closely monitor the patient throughout the infusion for any signs of infusion-related reactions or adverse effects. Vital signs, like the heart rate, blood pressure, and oxygen levels, might be monitored during the procedure. 
• Post-infusion observation: After the infusion, the patient may be observed for a period to ensure no immediate adverse reactions or side effects. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: olipudase alfa 

Why do we use olipudase alfa? 

olipudase alfa is used for the treatment of acid sphingomyelinase deficiency (ASMD), which is also known as Niemann-Pick disease type B. ASMD is an infrequent genetic disorder caused by a deficiency of the enzyme acid sphingomyelinase, leading to the accumulation of sphingomyelin in various organs and tissues of the body. 

olipudase alfa is primarily used to replace the deficient or absent acid sphingomyelinase enzyme in patients with ASMD. By doing so, olipudase alfa helps to break down sphingomyelin into ceramide and other products, reducing the accumulation of sphingomyelin in cells and tissues. 

The goals of using olipudase alfa in patients with ASMD are to: 

• Alleviate Symptoms: By reducing the buildup of sphingomyelin, olipudase alfa may help alleviate the symptoms associated with ASMD. These symptoms can vary but may include hepatomegaly (liver enlargement), splenomegaly (spleen enlargement), respiratory issues, growth impairment, and bone involvement. 
• Slow Disease Progression: olipudase alfa aims to slow the progression of ASMD, helping to prevent or delay the worsening of symptoms and organ damage associated with the disease.