Chiesi Global Rare Diseases and Protalix BioTherapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved ELFABRIO (pegunigalsidase alfa-iwxj) in the United States for the treatment of adult patients with Fabry disease. ELFABRIO is a PEGylated enzyme replacement therapy (ERT). It is a recombinant human a-Galactosidase-A enzyme expressed in plant-cell culture that is designed to provide a long half-life.

The safety, tolerability, and efficacy of ELFABRIO has been studied in a comprehensive clinical development program in more than 140 patients with up to 7.5 years of follow up treatment. It has been studied in both ERT-naïve and ERT-experienced patients, including a head-to-head trial that met its primary endpoint with ELFABRIO demonstrating non-inferior efficacy to agalsidase beta in controlling estimated glomerular filtration rate (eGFR) decline, and in which ELFABRIO was generally well-tolerated with the majority of adverse events being mild or moderate in severity. ELFABRIO has an initial half-life of 78.9 ± 10.3 hours.

Clinical studies have not established that half-life results in superior efficacy or safety based on clinically relevant end points. Elfabrio® (pegunigalsidase alfa-iwxj) is indicated for the treatment of adults with confirmed Fabry disease. Prior to Elfabrio administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids.

Inform patients and caregivers of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions (IARs), and instruct them to seek medical care immediately if such symptoms occur. If a severe hypersensitivity reaction (including anaphylaxis) or severe IAR occurs, immediately discontinue Elfabrio administration and initiate appropriate medical treatment. If a mild to moderate hypersensitivity reaction or IAR occurs, consider slowing the infusion rate or temporarily withholding the dose.

?In clinical trials, 20 (14%) Elfabrio-treated patients experienced hypersensitivity reactions. Four Elfabrio-treated patients (3%) experienced anaphylaxis reactions that occurred within 5 to 40 minutes of the start of the initial infusion. The signs and symptoms of hypersensitivity reactions and anaphylaxis 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.

In clinical trials, 41 (29%) Elfabrio-treated patients experienced one or more infusion-associated reactions, including hypersensitivity, 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. A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitor serum creatinine and urinary protein-to-creatinine ratio.

If glomerulonephritis is suspected, discontinue treatment until a diagnostic evaluation can be conducted. When switching to Elfabrio from a prior enzyme replacement therapy, the risk of hypersensitivity reactions and infusion-associated reactions may be increased in certain patients with pre-existing anti-drug antibodies (ADAs). Consider monitoring IgG and IgE ADAs and clinical or pharmacodynamic response (eg, plasma lyso-Gb3 levels).

The most common adverse reactions (=15%) were infusion-associated reactions, nasopharyngitis, headache, diarrhea, fatigue, nausea, back pain, pain in extremity, and sinusitis.