Elfabrio

ELFABRIO is indicated for the treatment of adults with confirmed Fabry disease.

Injection: 20 mg/10 mL or 5 mg/2.5 mL (2 mg/mL) of pegunigalsidase alfa-iwxj in a clear and colorless solution in a single-dose vial.

The following clinically significant adverse reactions are described elsewhere in labeling:

• Hypersensitivity Reactions Including Anaphylaxis 
  [see Warnings and Precautions (
  5.1

  Hypersensitivity Reactions

  Including

  Anaphylaxis

  Hypersensitivity reactions including anaphylaxis have been reported in ELFABRIO-treated patients. In clinical trials, 20 (14%) of ELFABRIO-treated patients experienced hypersensitivity reactions. In these trials, 4 ELFABRIO-treated patients (3%; 1 naïve to enzyme replacement therapy (ERT) and 3 ERT-experienced patients) experienced anaphylaxis during the initial infusion and were positive for anti-pegunigalsidase alfa-iwxj IgE antibodies (referred to as IgE ADA)

  [see Adverse Reactions (

  6.1

  6.000000000000000e+00

  1

  )

  and

  Clinical Pharmacology (

  12.6

  )

  ]

  . The risk of pegunigalsidase alfa-iwxj-related hypersensitivity may be increased in certain patients with pre-existing ADA from prior ERT

  [

  see

  Use In Specific Populations (

  8.6

  )].

  Anaphylaxis (reported as Type I hypersensitivity reaction, hypersensitivity reaction, or bronchospasm) occurred within 5 to 40 minutes of the start of the initial infusion. Signs and symptoms included headache, nausea, vomiting, throat tightness, facial and oral edema, truncal rash, tachycardia, hypotension, rigors, urticaria, intense pruritus, moderate upper airway obstructions, macroglossia, and mild lip edema. Patients received treatment that included epinephrine, antihistamines and/or systemic corticosteroids.

  Prior to ELFABRIO administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. 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. Consider the risks and benefits of re-administering ELFABRIO following severe hypersensitivity reactions (including anaphylaxis). Patients may be rechallenged using slower infusion rates. In patients with severe hypersensitivity reaction, desensitization measures to ELFABRIO may be considered. If the decision is made to readminister ELFABRIO, ensure the patient tolerates the infusion. If the patient tolerates the infusion, the rate may be increased to reach the recommended rate.
    
    
  • If a
    mild or moderate
    hypersensitivity reaction occurs, consider temporarily holding the infusion or slowing the infusion rate
    [
    see Dosage and Administratio
    n (
    2.3
    )
    ]
    .

  Consider monitoring patients who demonstrate hypersensitivity reactions during ELFABRIO treatment for the presence of IgG and IgE ADA

  [see Clinical Pharmacology (

  12.6

  )]

  .
  )
  ]
  
  
  
• Infusion-Associated Reactions (IARs)
  [see Warnings and Precautions (
  5.2

  Infusion

  -

  Associated

  Reactions

  Infusion-associated reactions (IARs) have been reported in ELFABRIO-treated patients. In clinical trials, 41 (29%) of ELFABRIO-treated patients experienced one or more IARs, defined as any adverse reaction with onset after start of the infusion and up to 24 hours after the end of infusion. The risk of pegunigalsidase alfa-iwxj-related IARs may be increased in certain patients with pre-existing ADA from prior ERT

  [

  see

  Use In Specific Populations (

  8.6

  )].

  IARs included anaphylaxis reactions during the initial ELFABRIO administration

  [see Warnings and Precautions (

  5.1

  )]

  .

  In addition to the hypersensitivity reactions described above

  [see Warnings and Precautions (

  5.1

  )]

  , other IARs included nausea, chills, pruritus, rash, 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

  [see Adverse Reactions (

  6.1

  )]

  .

  Up to 40% of patients were pretreated with diphenhydramine, prednisone and/or acetaminophen at least once during the clinical trials. Severe reactions in the trials were generally managed with administration of antipyretics, antihistamines, corticosteroids, intravenous fluids, and/or oxygen.

  IARs were more frequently observed in ELFABRIO-treated patients who developed IgG anti-drug antibodies (ADA) including patients who had pre-existing IgG ADA

  [see

  Adverse Reactions (

  6.1

  6.1

  )

  and

  Clinical Pharmacology (

  12.6

  )

  ]

  . Consider monitoring patients who demonstrate IARs during ELFABRIO treatment for the presence of IgG and IgE ADA.

  Patients with advanced Fabry disease may have compromised cardiac function which may predispose them to a higher risk of severe complications from IARs. Closely monitor patients with compromised cardiac function if ELFABRIO is administered to these patients.

  Prior to ELFABRIO administration, consider pre-treating with antihistamines, antipyretics, and/or corticosteroids to reduce the risk of IARs. However, IARs may still occur in patients after receiving pre-treatment.

  • If a
    severe
    IAR occurs, discontinue ELFABRIO immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering ELFABRIO following a severe IAR. Patients may be rechallenged using slower infusion rates. Once a patient tolerates the infusion, the infusion rate may be increased to reach the recommended infusion rate.
    
    
  • If a
    mild or moderate
    IAR occurs, consider temporarily holding the infusion or slowing the infusion rate
    [see Dosage and Administration (
    2.3
    )]
    .
  )]
  
  
  
• Membranoproliferative Glomerulonephritis
  [see Warnings and Precautions (
  5.3

  Membranoproliferative

  Glomerulonephritis

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

  [see Adverse Reactions

  (

  6.1

  )

  ]

  . This event led to a decline in renal function that slowly improved upon discontinuation of ELFABRIO but did not return to baseline by the end of the trial. Monitor serum creatinine and urinary protein to creatinine ratio. If glomerulonephritis is suspected, discontinue ELFABRIO until a diagnostic evaluation can be conducted.
  )]

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 (

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.