Pegvisomant

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]

Pegvisomant
Clinical data
Trade namesSomavert
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: B3
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Identifiers
CAS Number
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC990H1532N262O300S7
Molar mass22 129 g·mol−1 (unpegylated)
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Discovery

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

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

Pegvisomant blocks the action of growth hormone on 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 the normalization of its levels can control the symptoms.[[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

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

.[10]

Other potential uses

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

References
  1. Schreiber I, Buchfelder M, Droste M, Forssmann K, Mann K, Saller B, Strasburger CJ (January 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. doi:10.1530/eje.1.02312. PMID 17218728.
  2. Freda PU, Gordon MB, Kelepouris N, Jonsson P, Koltowska-Haggstrom M, van der Lely AJ (March 2015). "Long-term treatment with pegvisomant as monotherapy in patients with acromegaly: experience from ACROSTUDY". Endocrine Practice. 21 (3): 264–74. doi:10.4158/EP14330.OR. PMC 4618502. PMID 25370326.
  3. Scientific Discussion of Somavert (PDF) (Report). European Medicines Agency. 2004.
  4. "Ohio University, inventors to receive up to $52 million from drug license transactions". Ohio University. Feb 15, 2011.
  5. Kopchick JJ (April 2003). "Discovery and mechanism of action of pegvisomant". European Journal of Endocrinology. 148 Suppl 2: S21-5. doi:10.1530/eje.0.148s021. PMID 12670297.
  6. Berryman DE, Palmer AJ, Gosney ES, Swaminathan S, DeSantis D, Kopchick JJ (2007). "Discovery and uses of pegvisomant: a growth hormone antagonist". Endokrynologia Polska. 58 (4): 322–9. PMID 18058724.
  7. CEDAC Final REcommendation on Reconsideration and Reasons for Recommendation: Pegvisomant (Somavert - Pfizer Canada Inc.) (PDF) (Report). Canadian Agency for Drugs and Technologies in Health. August 2, 2006.
  8. Neggers SJ, Muhammad A, van der Lely AJ (2015). "Pegvisomant Treatment in Acromegaly". Neuroendocrinology. 103 (1): 59–65. doi:10.1159/000381644. PMID 25792221. S2CID 19588354.
  9. Feenstra J, van Aken MO, de Herder WW, Feelders RA, van der Lely AJ (June 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. doi:10.1530/eje.1.02160. PMID 16728538.
  10. Moore DJ, Adi Y, Connock MJ, Bayliss S (October 2009). "Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation". BMC Endocrine Disorders. 9: 20. doi:10.1186/1472-6823-9-20. PMC 2768727. PMID 19814797.
  11. Evans A, Jamieson SM, Liu DX, Wilson WR, Perry JK (August 2016). "Growth hormone receptor antagonism suppresses tumour regrowth after radiotherapy in an endometrial cancer xenograft model". Cancer Letters. 379 (1): 117–23. doi:10.1016/j.canlet.2016.05.031. PMID 27241667.
  12. Divisova J, Kuiatse I, Lazard Z, Weiss H, Vreeland F, Hadsell DL, et al. (August 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. doi:10.1007/s10549-006-9168-1. PMID 16541323. S2CID 6234700.
  • "Pegvisomant". Drug Information Portal. U.S. National Library of Medicine.
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