Pegunigalsidase alfa; Recombinant Human α-galactosidase-A

Specification

• Cat#: THP-1101
• Product Name: Pegunigalsidase alfa; Recombinant Human α-galactosidase-A
• Description: Pegunigalsidase alfa is a recombinant form of human α-galactosidase-A indicated for long-term enzyme replacement therapy in patients with Fabry disease.
• Sequences: GLDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQVTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWAVAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENTMQMSLKDLLSEKDEL
• Species: Human
• Molecular Weight: 116000.0 Da (homodimer with two pegylated subunits)
• Introduction: Pegunigalsidase alfa is a recombinant form of human α-galactosidase-A indicated for long-term enzyme replacement therapy in patients with Fabry disease, a rare genetic disorder characterized by the deficiency of alpha-galactosidase A. Unlike other forms of recombinant alpha-galactosidase A, such as agalsidase alfa and agalsidase beta, pegunigalsidase alfa uses a plant cell-based protein expression system, leading to a different glycosylation pattern. While agalsidase alfa and agalsidase beta enter lysosomes via the mannose-6-phosphate (M6P) receptor, pegunigalsidase alfa carries no M6P on its glycans and does not depend on the M6P receptor during cellular uptake. Furthermore, the pegylation of pegunigalsidase alfa promotes higher stability and a longer half-life, allowing it to reach target organs with a lower dose and frequency of administration. In May 2023, the EMA granted marketing authorization to pegunigalsidase alfa in the European Union (EU) for the treatment of adult patients with Fabry disease. Later on, the FDA approved pegunigalsidase alfa for the treatment of adult patients with Fabry disease that same month.
• Cas No: 1644392-61-9
• Formula: C2060H3130N552O601S27
• Biologic Classification: Protein Based Therapies Recombinant Enzymes
• Physical Appearance: Liquid

Pharmaceutical Information

• Pharmacodynamics: In patients with Fabry disease, the use of pegunigalsidase alfa led to a mean decrease in peritubular capillary globotriaosylceramide (GB3) content of 67.8% ± 8.9% after 6 months. At the 6-months time point, most patients had their GB3 levels reduced by more than half. The use of pegunigalsidase alfa is associated with infusion-related reactions, hypersensitivity reactions and immunogenicity. The use of enzyme replacement therapies such as pegunigalsidase alfa may lead to depositions of immune complexes as a manifestation of immunological response. During the clinical development of pegunigalsidase alfa, a single case of glomerulonephritis membranoproliferative was reported. This led to a temporary decline in renal function, which improved upon the discontinuation of pegunigalsidase alfa.
• Mechanism of action: Fabry disease is an X-linked recessive disorder caused by mutations in the GLA gene that lead to the loss of function of α-galactosidase A. This α-galactosidase A deficiency leads to the accumulation of globotriaosylceramide (GB3) and other neutral glycosphingolipids throughout the body, including the heart, kidney, nervous system, vascular endothelium and smooth muscle. This accumulation of GB3 is characterized by chronic pain, ocular opacities, liver and kidney impairment, skin lesions, vascular deterioration and cardiac deficiencies. Pegunigalsidase alfa is a pegylated recombinant form of human α-galactosidase-A, with an amino acid sequence similar to the human enzyme that replaces α-galactosidase-A. It promotes the hydrolysis of the terminal α-galactosyl moieties of oligosaccharides and polysaccharides in the lysosome, reducing the amount of GB3 accumulated in patients with Fabry disease. The deacylated form of GB3, globotriaosylsphingosine (lyso-GB3), also plays a role in the development of Fabry disease, and the use of pegunigalsidase alfa decreases the accumulation of this metabolite as well.
• Affected organisms: Humans and other mammals
• Targets: 1. Globotriaosylceramide