Peringatan Keamanan

During clinical studies, no cases of pegunigalsidase alfa overdose were reported. No specific signs and symptoms were identified with the maximum dose of pegunigalsidase alfa used (2 mg/kg body weight every two weeks). Infusion-related reactions and pain in extremities were the most commonly reported adverse reactions. If an overdose is suspected, seek emergency medical attention.L46342

Pegunigalsidase alfa

DB14992

biotech approved investigational

Deskripsi

Pegunigalsidase alfa (PRX-102) is a recombinant form of human ?-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.A259352,L46342 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.A259347,A259352

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.L46342,L46387 Later on, the FDA approved pegunigalsidase alfa for the treatment of adult patients with Fabry disease that same month.L46432,L46437

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Pegunigalsidase alfa given in two-week intervals has a plasma half-life that ranges from 53 to 134 hours across dose groups and visit day.[L46342]
Volume Distribusi In enzyme replacement therapy-naïve patients with Fabry disease given an intravenous infusion of 1 mg/kg of pegunigalsidase alfa every two weeks, the volume of distribution was 321 mL/kg on day 1, 271 mL/kg on week 13, 226 mL/kg on week 26, and 186 mL/kg on week 52.[L46432]
Klirens (Clearance) Patients treated with 1 and 2 mg/kg of pegunigalsidase alfa every two weeks had a higher half-life and AUC with increasing duration of treatment, as well as lower clearance and elimination volume of distribution, suggesting a saturated clearance.[L46342] In enzyme replacement therapy-naïve patients with Fabry disease given an intravenous infusion of 1 mg/kg of pegunigalsidase alfa every two weeks, clearance was 2.9 mL/h/kg on day 1, 2.3 mL/h/kg on week 13, 1.6 mL/h/kg on week 26, and 1.1 mL/h/kg on week 52.[L46432]

Absorpsi

The pharmacokinetic profile of pegunigalsidase alfa at 0.2, 1, and 2 mg/kg administered every two weeks was evaluated in adult patients with Fabry disease. At these dose levels, the AUC0-? of pegunigalsidase alfa increased with increasing doses on day one and throughout the study. Also, the mean values for dose-normalized AUC0-2wk were for all doses, suggesting that pegunigalsidase alfa follows a linear dose-proportional pharmacokinetic profile.L46342 In enzyme replacement therapy-naïve patients with Fabry disease given an intravenous infusion of 1 mg/kg of pegunigalsidase alfa every two weeks, the Cmax went from 11.1 ?g/mL on day 1 to 17.3 ?g/mL on week 52, and the AUCinf went from 391 ?g·h/mL on day 1 to 1428 ?g·h/mL on week 52. In enzyme replacement therapy-experienced patients with Fabry disease given the same dose, the Cmax ranged from 21.2 to 23.3 ?g/mL, and the AUCtau ranged from 958 to 1074 ?g·h/mL.L46432

Metabolisme

As a recombinant protein, pegunigalsidase alfa is expected to be metabolized through peptide hydrolysis. Therefore, impaired liver function is not expected to have a clinically significant effect on the pharmacokinetics of pegunigalsidase alfa. Based on its metabolism, pegunigalsidase alfa is an unlikely target of cytochrome P450 enzymes.L46342

Rute Eliminasi

Pegunigalsidase alfa has a molecular weight of approximately 116 kDa, which is twice the cut-off value for glomerular filtration. Because of this, filtration and/or proteolytic degradation in kidneys is unlikely.L46342

Interaksi Obat

0 Data
Tidak ada data.

Target Protein

Alpha-galactosidase A GLA
Globotriaosylceramide

Referensi & Sumber

Synthesis reference: Shulman, A., et al. (2012). Nucleic acid construct for expression of alpha-galactosidase in plants and plant cells (WO 2012/098537 A1). World Intellectual Property Organization. https://patentimages.storage.googleapis.com/2c/14/4c/4f9fd78e7edb77/AU2011356137A1.pdf
Artikel (PubMed)
  • PMID: 25155442
    Kizhner T, Azulay Y, Hainrichson M, Tekoah Y, Arvatz G, Shulman A, Ruderfer I, Aviezer D, Shaaltiel Y: Characterization of a chemically modified plant cell culture expressed human alpha-Galactosidase-A enzyme for treatment of Fabry disease. Mol Genet Metab. 2015 Feb;114(2):259-67. doi: 10.1016/j.ymgme.2014.08.002. Epub 2014 Aug 10.
  • PMID: 29698600
    Ruderfer I, Shulman A, Kizhner T, Azulay Y, Nataf Y, Tekoah Y, Shaaltiel Y: Development and Analytical Characterization of Pegunigalsidase Alfa, a Chemically Cross-Linked Plant Recombinant Human alpha-Galactosidase-A for Treatment of Fabry Disease. Bioconjug Chem. 2018 May 16;29(5):1630-1639. doi: 10.1021/acs.bioconjchem.8b00133. Epub 2018 May 3.
  • PMID: 33379210
    Azevedo O, Gago MF, Miltenberger-Miltenyi G, Sousa N, Cunha D: Fabry Disease Therapy: State-of-the-Art and Current Challenges. Int J Mol Sci. 2020 Dec 28;22(1):206. doi: 10.3390/ijms22010206.
  • PMID: 30834538
    Schiffmann R, Goker-Alpan O, Holida M, Giraldo P, Barisoni L, Colvin RB, Jennette CJ, Maegawa G, Boyadjiev SA, Gonzalez D, Nicholls K, Tuffaha A, Atta MG, Rup B, Charney MR, Paz A, Szlaifer M, Alon S, Brill-Almon E, Chertkoff R, Hughes D: Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial. J Inherit Metab Dis. 2019 May;42(3):534-544. doi: 10.1002/jimd.12080. Epub 2019 Apr 8.

Contoh Produk & Brand

Produk: 8 • International brands: 0
Produk
  • Elfabrio
    Injection, solution, concentrate • 20 mg/10mL • Intravenous • US • Approved
  • Elfabrio
    Injection, solution, concentrate • 5 mg/2.5mL • Intravenous • US • Approved
  • Elfabrio
    Injection, solution, concentrate • 2 mg/mL • Intravenous • EU • Approved
  • Elfabrio
    Injection, solution, concentrate • 2 mg/mL • Intravenous • EU • Approved
  • Elfabrio
    Injection, solution, concentrate • 2 mg/mL • Intravenous • EU • Approved
  • Elfabrio
    Injection, solution, concentrate • 2 mg/mL • Intravenous • EU • Approved
  • Elfabrio
    Injection, solution, concentrate • 2 mg/mL • Intravenous • EU • Approved
  • Elfabrio
    Injection, solution, concentrate • 2 mg/mL • Intravenous • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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