Pegunigalsidase Alfa-iwxj (Monograph)

Brand name: Elfabrio
Drug class: Enzymes

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Warning

Patients treated with pegunigalsidase alfa-iwxj have experienced hypersensitivity reactions, including anaphylaxis.
Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available.
If a severe hypersensitivity reaction occurs, discontinue pegunigalsidase alfa-iwxj immediately and initiate appropriate medical treatment.
In patients with severe hypersensitivity reaction, a desensitization procedure to pegunigalsidase alfa-iwxj may be considered.

Introduction

PEGylated recombinant human α-galactosidase A.

Uses for Pegunigalsidase Alfa-iwxj

Fabry Disease

Used as an enzyme replacement therapy (ERT) in adults with Fabry disease.

Has been shown to reduce renal Gb3 inclusions (surrogate endpoint) in the peritubular capillaries; also demonstrated comparable effects to agalsidase beta on eGFR.

In patients with Fabry disease, a treatment regimen consisting of ERT and adjunctive therapies for prevention of disease progression and symptom control recommended. Initiation of ERT is guided by phenotype, gender, and presence of symptoms. Early initiation of ERT should be considered when appropriate.

Pegunigalsidase alfa has a prolonged circulatory half-life compared to other ERTs. PEGylation may contribute to decreased immunogenicity.

Pegunigalsidase Alfa-iwxj Dosage and Administration

General

Patient Monitoring

Monitor patients closely during pegunigalsidase alfa infusions; severe hypersensitivity reactions, including anaphylaxis, and infusion-associated reactions have occurred. Ensure that appropriate medical support measures, including cardiopulmonary resuscitation equipment, are available during administration.
Monitor patients with advanced Fabry disease and compromised cardiac function during pegunigalsidase alfa infusions, as these patients may be at increased risk of severe complications from infusion-associated reactions.
Monitor S_cr and urinary protein to creatinine ratio (UPCR) during treatment.
Consider monitoring clinical or pharmacodynamic response (e.g., plasma lyso-Gb3 levels) when switching from agalsidase beta to pegunigalsidase alfa in patients with pre-existing anti-drug antibodies (ADAs).
Consider monitoring for the presence of IgG and IgE ADAs in patients who experience infusion-associated reactions during pegunigalsidase alfa administration.

Premedication and Prophylaxis

In enzyme replacement therapy (ERT)-experienced patients, if pretreatment with antihistamines, antipyretics, and/or corticosteroids was used with prior ERT infusions, consider similar pretreatment with pegunigalsidase alfa. After 4 to 6 pegunigalsidase alfa infusions, a stepwise decrease in pretreatment medications and/or discontinuation may be considered if treatment was tolerated.
In ERT-naïve patients, pretreatment with antihistamines, antipyretics, and/or corticosteroids may be considered.

Administration

IV Infusion

Administer by IV infusion after dilution.

Available as a 20 mg/10 mL or 5 mg/2.5 mL clear and colorless solution in a single-dose vial. Must dilute commercially available injection with 0.9% sodium chloride injection prior to administration.

Use an in-line, low protein-binding, 0.2 micron filter during administration.

Once infusion is complete, flush IV line with 0.9% sodium chloride injection using the same infusion rate used for the last part of the pegunigalsidase alfa infusion.

Do not infuse pegunigalsidase alfa-iwxj in the same IV line with other medications.

Home infusion: may consider in patients who have reached an infusion duration that is well tolerated; the decision to transition a patient to home treatment should be made after evaluation and recommendation by a healthcare provider. Home treatment should continue under the supervision of a healthcare provider. Maintain the infusion duration during home administration and only change in a healthcare facility. If a dose is missed or delayed, contact a healthcare provider.

Dilution

Determine number of vials to be diluted based on actual body weight; round to the next whole number.

Remove vials from refrigeration and allow to sit for 15–30 minutes at room temperature (20–25°C). Do not use an external heat source to heat vials.

Visually inspect solution for particulate matter and discoloration; discard if present.

Dilute pegunigalsidase alfa-iwxj in 0.9% sodium chloride injection to a total volume based on actual body weight (see Table 1 or Table 2 depending on the patient's prior ERT use status). Prior to adding the volume of pegunigalsidase alfa-iwxj required for the dose, remove an equal volume of 0.9% sodium chloride from the infusion bag.

Table 1: Recommended Total Infusion Volume and Infusion Rate for ERT-Experienced Patients Based on Actual Body Weight1
Actual Body Weight	Total Infusion Volume	Infusion Rate
<70 kg	150 mL	0.83 mL/minute (50 mL/hour)
70–100 kg	250 mL	1.39 mL/minute (83 mL/hour)
>100 kg	500 mL	2.78 mL/minute (167 mL/hour)

Table 2: Recommended Total Infusion Volume and Infusion Rate for ERT-Naïve Patients Based on Actual Body Weight1
Actual Body Weight	Total Infusion Volume	Infusion Rate
<70 kg	150 mL	0.63 mL/minute (37.5 mL/hour)
70–100 kg	250 mL	1 mL/minute (60 mL/hour)
>100 kg	500 mL	1.38 mL/minute (83 mL/hour)

Withdraw volume of pegunigalsidase alfa-iwxj required for the dose from the vials (discard any unused solution remaining in the vial), and add directly into the 0.9% sodium chloride infusion bag.

Gently invert infusion bag to mix solution. Avoid vigorous shaking or agitation.

Rate of Administration

Rate of administration for the initial 4–6 infusions is based on actual body weight and prior treatment with ERT (see Table 1 or Table 2 depending on patient's previous ERT status). Infusion rates listed in the tables may be increased if patient tolerates the first 4–6 infusions; infusion rate may be slowed in case of a hypersensitivity reaction or an infusion-associated reaction. If patient tolerates the initial 4–6 infusions, may decrease the duration of every third infusion in decrements of 30 minutes as tolerated. Minimum recommended infusion time is 1.5 hours.

In patients previously treated with ERT with an infusion duration >3 hours, use the same infusion rate for the pegunigalsidase alfa infusion. May decrease the duration of every third infusion after the initial 4–6 infusion in decrements of 30 minutes as tolerated.

Dosage

Dosage of pegunigalsidase alfa-iwxj is based on actual body weight.

Adults

Fabry Disease

IV

1 mg/kg via IV infusion every 2 weeks. Infusion rates dependent on total infusion volume and prior treatment with ERT, as outlined in Table 1 and Table 2.

If ≥1 doses are missed, restart pegunigalsidase alfa infusions as soon as possible. Do not double a dose to compensate for a missed dose.

Dosage Modification for Infusion Reactions

IV

If a severe hypersensitivity or infusion-associated reaction occurs, immediately discontinue administration and initiate appropriate medical treatment.

If a mild to moderate hypersensitivity or infusion-associated reaction occurs, consider temporarily holding the infusion for 15–30 minutes or slowing infusion rate by 25% to 50%. If symptoms persist despite holding or slowing infusion, stop infusion and monitor patient. Consider re-initiating infusion in 7–14 days at 25% to 50% of the rate at which the reaction occurred with appropriate pretreatment. If symptoms subside after holding infusion, resume infusion at a 25% to 50% reduced rate as tolerated. Alternatively, if symptoms subside after slowing infusion, complete infusion at reduced rate as tolerated. With next infusion, increase infusion rate by increments of 25% every third infusion as tolerated until the infusion rate at which the reaction occurred is reached.

Special Populations

Hepatic Impairment

No special population dosage recommendations at this time.

Renal Impairment

No special population dosage recommendations at this time.

Geriatric Patients

No special population dosage recommendations at this time.

Cautions for Pegunigalsidase Alfa-iwxj

Contraindications

None.

Warnings/Precautions

Warnings

Hypersensitivity Reactions

Risk of serious hypersensitivity reactions, including anaphylaxis (see Boxed Warning). Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available.

If a severe hypersensitivity reaction occurs, discontinue pegunigalsidase alfa immediately and initiate appropriate medical treatment.

Risk of hypersensitivity reactions may be increased in patients with ADAs from prior ERT.

Other Warnings and Precautions

Infusion-Associated Reactions

Infusion-associated reactions reported; most common symptoms were anaphylaxis, nausea, chills, rash, pruritus, chest pain, dizziness, vomiting, asthenia, pain, sneezing, dyspnea, nasal congestion, throat irritation, abdominal pain, erythema, diarrhea, burning sensation, neuralgia, headache, paresthesia, tremor, agitation, increased body temperature, flushing, bradycardia, myalgia, hypertension, and hypotension. Risk may be increased in patients with ADAs from prior ERT.

If a severe infusion-associated reaction occurs, discontinue pegunigalsidase alfa immediately and initiate appropriate medical treatment. If a mild or moderate infusion-associated reaction occurs, consider holding or slowing the infusion rate.

Membranoproliferative Glomerulonephritis

A case of membranoproliferative glomerulonephritis with immune depositions in the kidney reported in clinical trials.

Monitor S_cr and UPCR. If glomerulonephritis suspected, discontinue pegunigalsidase alfa until a diagnostic evaluation can be conducted.

Immunogenicity

IgG and IgE ADAs detected. Potential for increased risk of hypersensitivity and infusion-related reactions in patients with ADAs, and potential for decreased plasma concentrations of pegunigalsidase alfa-iwxj and decreased efficacy of the drug.

Specific Populations

Pregnancy

No available data on pegunigalsidase alfa use in pregnant women. However, pegunigalsidase alfa, as an enzyme replacement, is not expected to cause adverse outcomes.

There is a pregnancy safety study for pegunigalsidase alfa. If a patient becomes pregnant while receiving pegunigalsidase alfa, healthcare providers should report pegunigalsidase alfa exposure by calling 1-888-661-9260 or visiting [Web].

Lactation

Not known whether pegunigalsidase alfa is distributed into human milk. Effects of pegunigalsidase alfa on breast-fed infants or milk production are not known.

Consider benefits of breastfeeding along with mother's need for pegunigalsidase alfa and any adverse effects on the breastfed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

There were no patients ≥65 years of age in clinical trials. Not known whether geriatric patients ≥65 years of age respond differently compared to younger patients.

Patients with Prior Enzyme Replacement Therapy

Patients who received prior ERT are more likely to have pre-existing ADAs to pegunigalsidase alfa. When switching from other ERT to pegunigalsidase alfa, pre-existing ADAs may reduce plasma pegunigalsidase alfa concentrations, which may reduce efficacy, and increase the risk of hypersensitivity and infusion-associated reactions.

Common Adverse Effects

Most common adverse reactions (≥15%): infusion-associated reactions, nasopharyngitis, headache, diarrhea, fatigue, nausea, back pain, pain in extremity, sinusitis.

Drug Interactions

No formal drug interaction studies performed to date.

Pegunigalsidase Alfa-iwxj Pharmacokinetics

Elimination

Metabolism

Expected to be metabolized by catabolic pathways into small peptides.

Half-life

With infusion time of approximately 5.5 hours: approximately 78.9±10.3 hours.

With infusion time of approximately 3.3 hours: approximately 121±22 hours.

Stability

Storage

Parenteral

Solution for Injection

Store vials in refrigerator at 2–8°C; do not freeze.

Store diluted solution under refrigeration at 2–8°C for up to 24 hours or at room temperature (20–25°C) for up to 8 hours.

Use within 8 hours at room temperature, inclusive of infusion time, or discard.

Actions

PEGylated recombinant human α-galactosidase A enzyme; thought to reduce accumulated Gb3.
Accumulated Gb3 is associated with organ damage, including renal impairment, cardiac disease, stroke, and early death.

Advice to Patients

Advise the patient and/or caregiver that reactions related to the infusion may occur during and after pegunigalsidase alfa treatment, including anaphylactic reactions, other serious or severe hypersensitivity reactions, and infusion-associated reactions. Inform the patient and/or caregiver of the signs and symptoms of hypersensitivity and infusion-associated reactions and to seek immediate medical care should these signs and symptoms occur.
Advise patients who are exposed to pegunigalsidase alfa-iwxj during pregnancy that there is a pregnancy safety study that monitors pregnancy outcomes. Encourage the patient to report the pregnancy to Chiesi USA, Inc. at 1-888-661-9260.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Pegunigalsidase alfa is available through Eversana™ Life Sciences Specialty Pharmacy. Contact Chiesi Total Care at 1-833-656-1056 or consult the Chiesi Total Care & Patient Support website for specific ordering and availability information ([Web]).