Pegloticase

Pegloticase
Clinical data
Trade names Krystexxa
AHFS/Drugs.com Monograph
MedlinePlus a611015
License data
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration		 Intravenous
ATC code M04AX02 (WHO)
Legal status
Legal status
Pharmacokinetic data
Bioavailability N/A
Biological half-life 10–12 days
Identifiers
CAS Number 885051-90-1 N
IUPHAR/BPS 7463
ChemSpider none
UNII R581OT55EA YesY
KEGG D09316 YesY
ChEMBL CHEMBL1237025 N
Chemical and physical data
Formula C1549H2430N408O448S8 (peptide monomer)
Molar mass 497 kg/mol (polymer-modified tetramer)
 NYesY (what is this?)  (verify)

Pegloticase (trade name Krystexxa, formerly Puricase)[1] is a drug for the treatment of severe, treatment-refractory, chronic gout, developed by Savient Pharmaceuticals.[2][3]

In September 2010, the FDA approved pegloticase for marketing in the United States after two clinical trials demonstrated the drug lowered uric acid levels and reduced deposits of uric acid crystals in joints and soft tissue. The European Medicines Agency (EMA) granted marketing authorization in January 2013 for treatment of disabling tophaceous gout. Pegloticase is the first drug approved for this indication. Krystexxa is currently marketed in the U.S. by Crealta Pharmaceuticals LLC.

The drug is administered by infusion intravenously under the direction of a rheumatologist.

Medical uses

It is an option for the 3% of people who are intolerant to other medications.[4] Pegloticase is given as an intravenous infusion every two weeks,[4] and has been found to reduce uric acid levels in this population.[5] It is likely useful for tophi but has a high rate of side effects.[6]

Side effects

In individuals with glucose-6-phosphate dehydrogenase deficiency, pegloticase may precipitate a severe, life-threatening hemolysis with methemoglobinemia; it is therefore contraindicated in such individuals. Pegloticase may also show immunogenicity.[7]

Mechanism of action

Pegloticase is a recombinant porcine-like uricase. Similarly to rasburicase, it metabolises uric acid to allantoin. This reduces the risk of precipitates, since allantoin is five to ten times more soluble than uric acid.

In contrast to rasburicase, pegloticase is pegylated to increase its elimination half-life from about eight hours to ten or twelve days, and to decrease the immunogenicity of the foreign uricase protein. This modification allows for an application just once every two to four weeks, making this drug suitable for long-term treatment.[8]

Chemistry

Pegloticase is a tetrameric protein composed of four identical chains of about 300 amino acids each. Approximately nine of the 30 lysine residues in each chain are pegylated. These PEG chains consist of about 225 ethylene glycol units each (10 kg/mol PEG).[2]

References

  1. ↑ Savient to Present Multiple Abstracts At the European League Against Rheumatism (EULAR) 2009 Annual Congress
  2. 1 2 Statement on a nonproprietary name adopted by the USAN Council
  3. ↑ Savient Pharmaceuticals: Uricase
  4. 1 2 "FDA approves new drug for gout". FDA. September 14, 2010.
  5. ↑ Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, Vázquez-Mellado J, White WB, Lipsky PE, Horowitz Z, Huang W, Maroli AN, Waltrip RW, Hamburger SA, Becker MA (Aug 17, 2011). "Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials". JAMA: the Journal of the American Medical Association. 306 (7): 711–20. doi:10.1001/jama.2011.1169. PMID 21846852.
  6. ↑ Sriranganathan, MK; Vinik, O; Bombardier, C; Edwards, CJ (Oct 20, 2014). "Interventions for tophi in gout". The Cochrane database of systematic reviews. 10 (10): CD010069. doi:10.1002/14651858.CD010069.pub2. PMID 25330136.
  7. ↑ Abraham J. Domb, Neeraj Kumar (2 August 2011). Biodegradable Polymers in Clinical Use and Clinical Development. John Wiley & Sons. ISBN 9781118015803.
  8. ↑ Biggers, K; Scheinfeldt, N (2008). "Pegloticase, a polyethylene glycol conjugate of uricase for the potential intravenous treatment of gout". Current Opinion in Investigational Drugs. 9 (4): 422–429. PMID 18393109.
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