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Pegunigalsidase Alfa

FDA Drug Information • Also known as: Elfabrio

Brand Names
Elfabrio
Drug Class
Hydrolytic Lysosomal Neutral Glycosphingolipid-specific Enzyme [EPC]
Route
INTRAVENOUS
Dosage Form
INJECTION, SOLUTION, CONCENTRATE
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with ELFABRIO have experienced hypersensitivity reactions, including anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during ELFABRIO administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ELFABRIO immediately and initiate appropriate medical treatment. In patients with severe hypersensitivity reaction, a desensitization procedure to ELFABRIO may be considered [see Warnings and Precautions ( 5.1 )] . WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS See full prescribing information for complete boxed warning. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs, discontinue ELFABRIO immediately and initiate appropriate medical treatment. ( 5.1 )

Description

11 DESCRIPTION Pegunigalsidase alfa-iwxj, a hydrolytic lysosomal neutral glycosphingolipid-specific enzyme, is a PEGylated and crosslinked, chemically modified, recombinant human alpha-galactosidase A enzyme that is produced by genetically modified Bright Yellow 2 ( Nicotiana tabacum ) plant cells. The amino acid sequence of one subunit of pegunigalsidase alfa-iwxj consists of 405 amino acids, of which 398 amino acids are identical to human alpha-GAL-A with an additional 6 amino acids (SEKDEL) included at the C-terminal to encode an endoplasmic retrieval signal, and an additional glycine at the N-terminus derived from the signal peptide. Pegunigalsidase alfa-iwxj is a homodimeric glycoprotein covalently crosslinked with an average of nine 2.3 kDa PEG per dimer. The total molecular weight of the cross-linked dimer is approximately 116 kDa. Pegunigalsidase alfa-iwxj has specific activity of approximately 35-62 U/mg (one enzyme unit is defined as the amount of enzyme which catalyzes the hydrolysis of one micromole of synthetic substrate, p-nitrophenyl-α-D-galactopyranoside per minute at 37°C). ELFABRIO (pegunigalsidase alfa-iwxj) injection is a sterile, preservative-free, 20 mg/10 mL or 5 mg/2.5 mL (2 mg/mL) solution in a single-dose vial for intravenous infusion after dilution. Each mL contains 2 mg of pegunigalsidase alfa-iwxj, anhydrous citric acid (0.2 mg), sodium chloride (7.06 mg), sodium citrate (6.73 mg), and Water for Injection, USP. The pH is approximately 5.9 to 6.4.

What Is Pegunigalsidase Alfa Used For?

1 INDICATIONS AND USAGE ELFABRIO is indicated for the treatment of adults with confirmed Fabry disease. ELFABRIO is a hydrolytic lysosomal neutral glycosphingolipid-specific enzyme indicated for the treatment of adults with confirmed Fabry disease. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For pretreatment recommendations, see Full Prescribing Information. ( 2.1 ) Recommended dosage is 1 mg/kg every 2 weeks administered as an intravenous infusion. ( 2.2 ) For dosage and administration modifications due to hypersensitivity reactions or infusion-associated reactions (IARs), see Full Prescribing Information. ( 2.3 ) For instructions on preparation (including dilution), storage, and administration (including rates for the initial 4-6 infusions for ERT-experienced and ERT-naïve patients), see Full Prescribing Information. ( 2.4 , 2.5 , 2.6 ) 2. 1 Recommendations Prior to ELFABRIO Treatment Pretreatment In enzyme replacement therapy (ERT)-experienced patients, if pretreatment with antihistamines, antipyretics, and/or corticosteroids was used prior to ERT administration, consider similar pretreatment with these medications before the first several ELFABRIO infusions. After 4 to 6 ELFABRIO infusions, a stepwise decrease in the pretreatment medication dose(s) and/or discontinuation of the pretreatment medication(s) may be considered if treatment with ELFABRIO was tolerated. In ERT-naïve patients, prior to ELFABRIO administration, pre-treating with antihistamines, antipyretics, and/or corticosteroids may be considered [see Warnings and Precautions ( 5.1 , 5.2 )] . Medical Support Appropriate medical support measures including cardiopulmonary resuscitation equipment should be readily available during ELFABRIO administration. 2. 2 Recommended Dosage and Administration The recommended dosage of ELFABRIO, based on actual body weight, is 1 mg/kg administered by intravenous infusion every 2 weeks. The initial recommended ELFABRIO infusion rates for ERT-experienced or ERT-naïve patients are based on actual body weight [ see Tables 1 and 2 ] . If one or more doses are missed, restart ELFABRIO treatment as soon as possible, maintaining the 2 week interval between infusions thereafter. Do not double a dose to compensate for a missed dose. 2. 3 Administration Modifications Due to Hypersensitivity Reactions and/or Infusion-Associated Reactions In the event of a severe hypersensitivity reaction (e.g., anaphylaxis) or severe infusion-associated reaction (IAR), immediately discontinue ELFABRIO administration and initiate appropriate medical treatment. For additional recommendations in the event of a severe hypersensitivity reaction or IAR, see Warnings and Precautions ( 5.1 , 5.2 ) . In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, consider temporarily holding the infusion for 15 to 30 minutes or slowing the infusion rate by 25% to 50% [ see Dosage and Administration ( 2.6 )] , and initiating appropriate medical treatment [see Warnings and Precautions ( 5.1 , 5.2 )] . If symptoms persist despite holding or slowing the infusion, stop the infusion and monitor the patient. Consider re-initiating the infusion within 7 to 14 days at 25% to 50% of the rate at which the reaction occurred with...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions ( 5.1 ) ] Infusion-Associated Reactions (IARs) [see Warnings and Precautions ( 5.2 )] Membranoproliferative Glomerulonephritis [see Warnings and Precautions ( 5.3 )] Most common adverse reactions (≥15%) are: infusion-associated reactions, nasopharyngitis, headache, diarrhea, fatigue, nausea, back pain, pain in extremity, and sinusitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chiesi USA, Inc. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions From Trial 2 The safety of ELFABRIO in adults with confirmed Fabry disease who had been previously treated with agalsidase beta was evaluated in Trial 2 which included a total of 52 ELFABRIO-treated patients (29 male, 23 female aged 20 to 60 years old) with Fabry disease [see Clinical Studies ( 14 )] . Patients received 1 mg/kg of ELFABRIO given intravenously every 2 weeks for at least 104 weeks. The most common adverse reactions (≥15%) reported with ELFABRIO were infusion-associated reactions which occurred in 17 patients (32%); followed by, nasopharyngitis and headache each in 11 patients (21%); diarrhea in 10 patients (19%); fatigue and nausea each in 9 patients (17%); and back pain, pain in extremity, and sinusitis each in 8 patients (15%) . One ELFABRIO-treated patient experienced a severe hypersensitivity reaction during the first infusion. The patient withdrew from the trial following a moderate hypersensitivity reaction during the second infusion. Table 3 lists adverse reactions reported in at least 5% of ELFABRIO-treated patients in Trial 2. Table 3: Adverse Reactions in Adults With Fabry Disease (Trial 2) 1 Adverse Reaction ELFABRIO N=52 n (%) Agalsidase beta N=25 n (%) Infusion-Associated Reaction 2,4 17 (32) 8 (32) Nasopharyngitis 11 (21) 4 (16) Headache 11 (21) 5 (20) Diarrhea 10 (19) 6 (24) Fatigue 9 (17) 4 (16) Nausea 9 (17) 3 (12) Back pain 8 (15) 5 (20) Pain in Extremity 8 (15) 4 (16) Sinusitis 8 (15) 3 (12) Abdominal Pain 6 (12) 0 (0) Proteinuria 6 (12) 0 (0) Hypersensitivity 3,4 5 (9) 4 (16) Upper Respiratory Tract Congestion 4 (8) 0 (0) Neuralgia 4 (8) 0 (0) Peripheral Neuropathy 3 (6) 0 (0) Sciatica 3 (6) 0 (0) Infusion Site Extravasation 3 (6) 0 (0) Hematuria 3 (6) 0 (0) 1 Adverse reactions were those that occurred in ≥ 5% of ELFABRIO-treated patients. 2 “Infusion-associated reaction” includes nausea, vomiting, abdominal pain, diarrhea, fatigue, chills, malaise, non-cardiac chest pain, hypersensitivity, body temperature increased, burning sensation, neuralgia, agitation, throat irritation, pruritic rash, and flushing. Events occurring within 24 hours. 3 “Hypersensitivity” includes macular rash, pruritic rash, and face swelling. Events occurring within 24 hours. 4 The events of hypersensitivity and pruritic rash fall in both hypersensitivity and IAR categories. Membranoproliferative Glomerulonephritis A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported in an ELFABRIO-treated patient. Immunogenicity: Anti - D rug Antibody-Associated Adverse Reactions Of the patients who experienced serious hypersensitivity reactions during the first ELFABRIO infusion and had pre-infusion samples and samples available for testing at the time of the event, all but one had pre-existing IgE ADAs and all tested positive for IgE ADAs at the time of the reaction. In the overall clinical program, IARs occurred in 51% (19/37) of patients who were IgG ADA positive at baseline compared to 16% (13/84) in IgG ADA...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data on ELFABRIO use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes; however, as an enzyme replacement, ELFABRIO is not expected to cause adverse outcomes . Animal reproduction studies have been conducted with pegunigalsidase alfa-iwxj in pregnant rats and rabbits. No adverse effects on embryofetal development were observed in pregnant rats intravenously administered pegunigalsidase alfa-iwxj twice per week at exposures up to 3.6 times that of the maximum recommended human dose (MRHD) (based on area under the concentration-time curve (AUC)). Maternal toxicity was observed in pregnant rabbits intravenously administered pegunigalsidase alfa-iwxj twice per week at doses that were ≥ 3.2 times the MRHD (based on human equivalent dose) [ see Data ] . The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. There is a pregnancy safety study for ELFABRIO. If a patient becomes pregnant while receiving ELFABRIO, healthcare providers should report ELFABRIO exposure by calling 1-888-661-9260 or visiting https://chiesirarediseases.com/contact-us/medical-information-form. Data Animal Data In an embryofetal development study in the rat, pegunigalsidase alfa-iwxj was administered during the period of organogenesis on gestation day 6, 9, 12, and 15. No maternal or fetal adverse effects were noted at exposures that were up to 3.6-fold greater than the recommended dose of 1 mg/kg every two weeks. In an embryofetal development study in the rabbit, administration of pegunigalsidase alfa-iwxj during the period of organogenesis on...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied ELFABRIO (pegunigalsidase alfa-iwxj) injection is a sterile, preservative-free, clear and colorless solution supplied in a single-dose vial. Each vial contains 20 mg/10 mL or 5 mg/2.5 mL (2 mg/mL) of pegunigalsidase alfa-iwxj. ELFABRIO is available as: One single-dose 20 mg/10 mLvial in a carton (NDC 10122-160-02) One single-dose 5 mg/2.5 mL vial in a carton (NDC 10122-165-02) Five single-dose 20 mg/10 mL vials in a carton (NDC 10122-160-05) Ten single-dose 20 mg/10 mL vials in a carton (NDC 10122-160-10) Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not shake.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.