pegunigalsidase alfa-iwxj

Action and Spectrum

Actions and Spectrum: 

• pegunigalsidase alfa-iwxj is an enzyme replacement therapy used to treat Fabry disease, a rare genetic disorder characterized by the deficiency of an enzyme called alpha-galactosidase A (α-Gal A). The mechanism of action of pegunigalsidase alfa-iwxj involves the replacement of the deficient or dysfunctional α-Gal A enzyme in patients with Fabry disease. 

• pegunigalsidase alfa-iwxj is a recombinant form of α-Gal A modified by attaching polyethylene glycol (PEG) chains to increase its circulating half-life. The PEGylation process helps extend the time the enzyme remains in the body, allowing for longer-lasting enzymatic activity. 

• Once administered, pegunigalsidase alfa-iwxj is taken up by cells and transported into lysosomes, which are compartments within cells involved in the breakdown and recycling of various substances. Within the lysosomes, pegunigalsidase alfa-iwxj functions as an enzyme and catalyzes the hydrolysis of globotriaosylceramide (GL-3). This lipid accumulates in the tissues of patients with Fabry disease due to the α-Gal A enzyme deficiency. 

• By breaking down GL-3, pegunigalsidase alfa-iwxj helps to reduce the accumulation of this lipid in various organs and tissues, including the kidneys, heart, and blood vessels. This enzymatic replacement therapy aims to alleviate the symptoms and slow the progression of Fabry disease by addressing the underlying deficiency of α-Gal A. 

• Regarding the spectrum of activity, pegunigalsidase alfa-iwxj is specifically designed to treat Fabry disease caused by mutations in the GLA gene. It is intended to provide enzymatic replacement therapy for patients with confirmed diagnoses and symptoms related to Fabry disease. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Nasopharyngitis (21%) 

Diarrhea (19%) 

Nausea (17%) 

Pain in extremity (15%) 

Abdominal pain (12%) 

Infusion-associated reaction (32%) 

Headache (21%) 

Fatigue (17%) 

Back pain (15%) 

Sinusitis (15%) 

Proteinuria (12%)  

1-10% 

Upper respiratory tract congestion (8%) 

Peripheral neuropathy (6%) 

Infusion site extravasation (6%) 

Hypersensitivity (9%) 

Neuralgia (8%) 

Sciatica (6%) 

Hematuria (6%)  

Frequency not defined 

1 patient had membraneoproliferative glomerulonephritis 

Black Box Warning

Black box warning: 

Hypersensitivity reactions, including anaphylaxis, have been reported using pegunigalsidase alfa-iwxj. Anaphylaxis is a severe and potentially life-threatening allergic reaction. It is advised to exercise caution and take appropriate measures during administration. 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis, have been reported using pegunigalsidase alfa-iwxj. Close monitoring for signs of hypersensitivity, such as difficulty breathing, swelling, rash, or dizziness, is crucial during and after administration. If a severe hypersensitivity reaction occurs, immediate discontinuation of the infusion and appropriate medical treatment should be initiated. 
• Infusion-Related Reactions: Infusion-related reactions, such as fever, chills, flushing, headache, or changes in blood pressure, may occur during or after administering pegunigalsidase alfa-iwxj. Monitoring these reactions and managing them appropriately is essential. 
• Immunogenicity: Like other protein-based therapies, pegunigalsidase alfa-iwxj can elicit an immune response, developing antibodies against the therapy. These antibodies’ clinical significance and potential impact on treatment efficacy or safety are still being studied. 
• Acute Kidney Injury: Patients with Fabry disease may already have kidney involvement, and there have been reports of acute kidney injury following initiating enzyme replacement therapy. Close monitoring of kidney function is essential, and dose adjustments may be necessary in patients with compromised renal function. 
• Pregnancy and Breastfeeding: The safety and efficacy of pegunigalsidase alfa-iwxj during pregnancy and breastfeeding have not been established. Before using this therapy in pregnant or breastfeeding individuals, it is essential to consider the potential risks and benefits. 
• Pediatric Use: The safety and effectiveness of pegunigalsidase alfa-iwxj in pediatric patients have not been established. Its use in the pediatric population should be determined based on individual considerations and in consultation with a pediatric specialist. 

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 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: 

pegunigalsidase alfa-iwxj acts as a replacement for the deficient or dysfunctional α-Gal A enzyme. It is a recombinant form of α-Gal A that has been modified by attaching polyethylene glycol (PEG) chains. This PEGylation extends the circulating half-life of the enzyme, allowing for more sustained enzymatic activity. 

Upon administration, pegunigalsidase alfa-iwxj is taken up by cells and transported into lysosomes, which are cellular compartments involved in the breakdown and recycling of various substances. Within the lysosomes, pegunigalsidase alfa-iwxj functions as an enzyme and catalyzes the hydrolysis of globotriaosylceramide (GL-3). This lipid accumulates in tissues due to α-Gal A deficiency. 

By breaking down GL-3, pegunigalsidase alfa-iwxj helps reduce this lipid accumulation in various organs and tissues, including the kidneys, heart, and blood vessels. This enzymatic replacement therapy aims to alleviate the symptoms and slow the progression of Fabry disease. 

Pharmacodynamics: 

The pharmacodynamics of pegunigalsidase alfa-iwxj are: 

Reduction of GL-3 Accumulation: 

• Fabry disease is characterized by the deficiency of the enzyme alpha-galactosidase A (α-Gal A), leading to the accumulation of GL-3 and related glycosphingolipids in tissues and organs. pegunigalsidase alfa-iwxj, as an enzyme replacement therapy, aims to supplement the deficient α-Gal A and reduce the accumulation of GL-3. 
• By providing exogenous α-Gal A activity, pegunigalsidase alfa-iwxj catalyzes the hydrolysis of GL-3 within lysosomes, which are cellular compartments involved in the breakdown of various substances. This enzymatic activity helps to degrade the accumulated GL-3 and related glycosphingolipids, potentially reducing their burden on tissues and organs affected by Fabry disease.

Clinical Effects: 

The reduction in GL-3 accumulation achieved through pegunigalsidase alfa-iwxj treatment is expected to have various clinical effects, including symptom improvement and slowing the progression of Fabry disease. Specific clinical benefits may include: 

• Renal Function: Reducing GL-3 accumulation in the kidneys may help preserve renal function and reduce the risk of renal complications, such as proteinuria, kidney failure, or dialysis. 

• Cardiac Function: Decreased GL-3 deposition in the heart may improve cardiac structure and function, reducing the risk of cardiovascular complications associated with Fabry disease.

• Vascular Health: Reducing GL-3 accumulation in blood vessels may improve vascular health and reduce the risk of vascular complications, such as stroke or peripheral vascular disease. 

• Pain Management: Fabry disease is often associated with neuropathic pain. Reducing GL-3 accumulation may help alleviate pain symptoms or reduce their severity. 

Pharmacokinetics: 

Absorption 

pegunigalsidase alfa-iwxj is administered intravenously. 

The peak plasma concentration of pegunigalsidase alfa-iwxj increases over time, with the highest concentration observed at week 52 (17.3 mcg/mL). 

The AUC (area under the concentration-time curve) of pegunigalsidase alfa-iwxj also increases over time, with the highest AUC observed at week 52 (1428 mcgh/mL).  

Distribution 

The volume of distribution (Vd) of pegunigalsidase alfa-iwxj decreases over time, with the lowest Vd observed at week 52 (186 mL/kg). 

There is no information provided about the protein binding of pegunigalsidase alfa-iwxj. 

Metabolism 

pegunigalsidase alfa-iwxj is expected to be metabolized into small peptides by catabolic pathways. 

No information is provided regarding the specific metabolic pathways or enzymes involved in the metabolism of pegunigalsidase alfa-iwxj.  

Elimination and Excretion 

The elimination half-life of pegunigalsidase alfa-iwxj increases over time, with the most prolonged half-life observed at week 52 (121 hours). 

The clearance of pegunigalsidase alfa-iwxj decreases over time, with the lowest clearance observed at week 52 (1.1 mL/hr/kg). 

Adminstartion

Administration: 

• Administration Route: pegunigalsidase alfa-iwxj is administered intravenously, typically through a peripheral vein or a central venous access device. 
• Infusion Duration: The infusion duration may vary based on the prescribed dose and patient tolerance. The healthcare provider will determine the appropriate infusion time. Typically, the infusion duration ranges from 1 to 2 hours. 
• Dilution: pegunigalsidase alfa-iwxj is usually a concentrated solution that requires dilution before administration. The healthcare provider will prepare the appropriate dilution based on the prescribed dosage and the volume of the solution required for the infusion. 
• Preparation: Before administration, the diluted pegunigalsidase alfa-iwxj solution should be visually inspected for particulate matter and discoloration. If any abnormalities are observed, the solution should not be used. 
• Administration: The diluted solution is administered intravenously using a sterile infusion set or an infusion pump. The healthcare provider will ensure proper intravenous line placement and monitor the patient during the infusion. 
• Frequency of Administration: The frequency of pegunigalsidase alfa-iwxj administration is typically determined by the healthcare provider based on the patient’s needs. The treatment regimen may involve regular infusions at specific intervals, such as weekly or every two weeks. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: pegunigalsidase alfa-iwxj 

Why do we use pegunigalsidase alfa-iwxj? 

pegunigalsidase alfa-iwxj is a medication used to treat Fabry disease, a genetic lysosomal storage disorder. The primary therapeutic use of pegunigalsidase alfa-iwxj is to alleviate the symptoms of Fabry disease and slow the condition’s progression. Here are the critical uses of pegunigalsidase alfa-iwxj: 

Fabry Disease: pegunigalsidase alfa-iwxj is indicated for treating Fabry disease in patients with a confirmed diagnosis. Fabry disease is caused by a deficiency of the alpha-galactosidase A (α-Gal A), leading to the accumulation of globotriaosylceramide (GL-3) and related glycosphingolipids in various organs and tissues. pegunigalsidase alfa-iwxj functions as an enzyme replacement therapy, providing exogenous α-Gal A activity and helping to reduce the accumulation of GL-3.