Pegvisomant

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Pegvisomant
Clinical data
Trade names Somavert
AHFS/Drugs.com Monograph
ATC code
Identifiers
CAS Number
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C990H1532N262O300S7
Molar mass 22129.0 g/mol (unpegylated)
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Pegvisomant (trade name Somavert) is a growth hormone receptor antagonist used in the treatment of acromegaly.[1] It is primarily used if the pituitary gland tumor causing the acromegaly cannot be controlled with surgery or radiation, and the use of somatostatin analogues is unsuccessful, but is also effective as a monotherapy.[2] It is delivered as a powder that is mixed with water and injected under the skin.[3]

Discovery[edit]

Pegvisomant was discovered at Ohio University in 1987 by Distinguished Professor John Kopchick and graduate student Wen Chen at the Edison Biotechnology Institute. After completing clinical trials, it was approved for the treatment of acromegaly by the FDA in 2003 and marketed by Pfizer.[4]

Structure[edit]

Pegvisomant is a protein containing 191 amino acid residues to which several polyethylene glycol polymers have been covalently bound in order to slow clearance from the blood.[3] The protein is a modified version of human growth hormone designed to bind to and block the growth hormone receptor. It is manufactured using genetically modified E. coli bacteria.[3]

Mechanism of action[edit]

Pegvisomant blocks the action of growth hormone at the growth hormone receptor to reduce the production of IGF-1.[5][6] IGF-1 is responsible for most of the symptoms of acromegaly, and normalising its levels may control the symptoms.[7]

Long-term treatment studies with pegvisomant as a monotherapy have shown it to be safe,[2] and to date it is the most effective treatment of acromegaly as both a monotherapy and in combination with somatostatin analogues.[8]

Side effects[edit]

Side effects of pegvisomant include reactions at the injection site, swelling of the limbs, chest pain, hypoglycemia, nausea and hepatitis.[9]

Blocking of the growth hormone receptor reduces feedback control of the growth hormone regulation, leading to approximately doubled GH levels.[10]

Other potential uses[edit]

Recent studies have shown the potential of using pegvisomant as an anti-tumor treatment for certain types of cancers, in combination with other treatments.[11][12]

See also[edit]

References[edit]

  1. ^ Schreiber, I; Buchfelder, M; Droste, M; Forssmann, K; Mann, K; Saller, B; Strasburger, C J (2007). "Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: Safety and efficacy evaluation from the German Pegvisomant Observational Study". European Journal of Endocrinology. 156 (1): 75–82. PMID 17218728. doi:10.1530/eje.1.02312. 
  2. ^ a b Freda, Pamela; Gordon, Murray; Kelepouris, Nicky; Jonsson, Peter; Koltowska-Haggstrom, Maria; Van Der Lely, A. (2015). "Long-Term Treatment with Pegvisomant as Monotherapy in Patients with Acromegaly: Experience from Acrostudy". Endocrine Practice. 21 (3): 264–74. PMC 4618502Freely accessible. PMID 25370326. doi:10.4158/EP14330.OR. 
  3. ^ a b c "Scientific Discussion of Somavert" (PDF). European Medicines Agency. 2004. 
  4. ^ [1], Ohio University, inventors to receive up to $52 million from drug license transactions
  5. ^ Kopchick, J. (2003). "Discovery and mechanism of action of pegvisomant". European Journal of Endocrinology. 148: S21–5. PMID 12670297. doi:10.1530/eje.0.148s021. 
  6. ^ Berryman, Darlene E.; Palmer, Amanda J.; Gosney, Elahu S.; Swaminathan, Svetha; DeSantis, Dave; Kopchick, John J. (2007). "Discovery and uses of pegvisomant: A growth hormone antagonist". Endokrynologia Polska. 58 (4): 322–9. PMID 18058724. 
  7. ^ Canadian Agency for Drugs and Technologies in Health, CEDAC Final REcommendation on Reconsideration and Reasons for Recommendation, Pegvisomant (Somavert - Pfizer Canada Inc.)
  8. ^ Neggers, Sebastian J.C.M.M.; Muhammad, Ammar; Van Der Lely, Aart Jan (2015). "Pegvisomant Treatment in Acromegaly". Neuroendocrinology. 103 (1): 59–65. PMID 25792221. doi:10.1159/000381644. 
  9. ^ Feenstra, J; Van Aken, M. O.; De Herder, W. W.; Feelders, R. A.; Van Der Lely, A. J. (2006). "Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant". European Journal of Endocrinology. 154 (6): 805–6. PMID 16728538. doi:10.1530/eje.1.02160. 
  10. ^ Moore, David J; Adi, Yaser; Connock, Martin J; Bayliss, Sue (2009). "Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: A systematic review and economic evaluation". BMC Endocrine Disorders. 9: 20. PMC 2768727Freely accessible. PMID 19814797. doi:10.1186/1472-6823-9-20. 
  11. ^ Evans, Angharad; Jamieson, Stephen M.F.; Liu, Dong-Xu; Wilson, William R.; Perry, Jo K. (2016). "Growth hormone receptor antagonism suppresses tumour regrowth after radiotherapy in an endometrial cancer xenograft model". Cancer Letters. 379 (1): 117–23. PMID 27241667. doi:10.1016/j.canlet.2016.05.031. 
  12. ^ Divisova, Jana; Kuiatse, Isere; Lazard, Zawaunyka; Weiss, Heidi; Vreeland, Franzanne; Hadsell, Darryl L.; Schiff, Rachel; Osborne, C. Kent; Lee, Adrian V. (2006). "The growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7 breast cancer xenograft growth". Breast Cancer Research and Treatment. 98 (3): 315–27. PMID 16541323. doi:10.1007/s10549-006-9168-1.