Pegaptanib

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General structural formula
Information on the active ingredient
Non-proprietary name Pegaptanib
other names NX1838, EYE001
Molecular formula

C 294 H 370 F 13 N 107 O 188 P 28 [C 2 H 4 O] n + m (pegaptanib)

C 294 H 342 F 13 N 107 Na 28 O 188 P 28 [C 2 H 4 O] n + m (pegaptanib-octacosasodium)

(n ≈ m ≈ 450)

Molar mass 9520.51  g · mol -1  (without  PEGylation )
~ 50,000 g · mol -1 (with PEGylation)
CAS number 222716-86-1 (pegaptanib octacosodium )
ATC code S01 LA03
DrugBank Entry for pegaptanib in the University of Alberta's DrugBank .
PubChem 56603655
Mechanism of action Inhibition of Vascular Endothelial Growth Factor (VEGF)

Pegaptanib ( acronym from the English PEG ylated apt amer a ngiogenesis i n h ib itor) is an inhibitor of the vascular endothelial growth factor ( VEGF inhibitor) and is used to treat wet age-dependent macular degeneration (AMD), a disease of the eye.

Pegaptanib is a pegylated , 2'-fluoro pyrimidine and 2'-O-methyl purine substituted 27 mer RNA - aptamer and was in December 2004 the first of the FDA -approved aptamer. With the introduction of superior forms of therapy, the active ingredient has lost its importance. In Germany it was therefore taken off the market.

development

Pegaptanib was developed by EyeTech Pharmaceuticals, Inc. and licensed to Pfizer . Pfizer funded the late-stage clinical trials and did the marketing. Pfizer is the manufacturer of the intra- vitreous ( intravitreal ) injection solution with the trade name Macugen . In 2014, the approval was transferred to PharmaSwiss Ceska Republika, a company in the Valeant Group.

The active ingredient is used in the form of its water-soluble sodium salt pegaptanib octacosasodium.

Mechanism of action

An aptamer is a single nucleic acid strand that specifically binds to a specific target (target molecule) ( key and lock principle ). Pegaptanib specifically binds to VEGF-A 165 , an extracellular protein that is newer an important role in the formation of blood vessels ( angiogenesis ), and for the increased permeability ( permeability plays) of blood vessels. Both are pathologically important processes in vision loss due to AMD.

The aptamer injected intravitreally , i.e. directly into the vitreous humor of the eye , is intended to stop the formation of new vessels ( neovascularization ) by antagonizing the responsible growth factor VEGF (Vascular Endothelial Growth Factor) .

effectiveness

Pegaptanib slows or stops the progression of wet macular degeneration. Long-term use of pegaptanib significantly reduces the incidence of severe vision loss compared to untreated patients. In a study published in 2004, the use of pegaptanib compared to sham-treated controls ( placebo ) found a significantly increased chance of constant or increased visual acuity. However, the question of whether other forms of therapy, such as the use of ranibizumab or PDT , are superior or equivalent and more cost-effective has not yet been clarified .

Pegaptanib is injected intravitreally once every six weeks in doses of 0.3 mg.

Side effects

In most cases, side effects were attributed to the injection procedure, so see for side effects of intravitreal injection

Web links

Individual evidence

  1. ↑ a b Nucleotide sequence: 5'-CGAAUCĀGUGĀĀUGCUUĀUĀCĀUCCG-3'-3'dT
    (with: G = 2'-O-methyl- guanosine , Ā = 2'-O-methyl- adenosine , A = adenosine , C = 2'- deoxy-2'-fluoro- cytidine , U = 2'-deoxy-2'-fluoro uridine and dT = 2'- deoxythymidine )
  2. ↑ WHO: The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances - 2013
  3. ↑ WHO: Addendum1 to "The use of stems in the selection of International Nonproprietary names (INN) for pharmaceutical substances" WHO / EMP / RHT / TSN / 2013.1
  4. ↑ EW Ng. et al .: Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease . In: Nature Reviews. Drug Discovery . tape 5 , no. 2 , 2006, p. 123-132 , doi : 10.1038 / nrd1955 , PMID 16518379 .
  5. ↑ C. Berg: VEGF inhibitors and supplements ; Pharmaceutical newspaper, issue 12/2016.
  6. ↑ Macugen on the website of EMA.
  7. ↑ Pegaptanib and ranibizumab for neovascular age-related macular degeneration: a systematic review . In: The British Journal of Ophthalmology . tape 91 , no. 9 , 2007, p. 1177–1182 , doi : 10.1136 / bjo.2007.118562 , PMID 17475698 , PMC 1954893 (free full text).
  8. ↑ Pegaptanib: a novel approach to ocular neovascularization . In: The Annals of Pharmacotherapy . tape 40 , no. 7–8 , 2006, pp. 1322-1326 , doi : 10.1345 / aph.1G604 , PMID 16849623 .
  9. ↑ pegaptanib for neovascular Age-Related Macular Degeneration . In: New England Journal of Medicine . tape 351 , no. 27 , 2004, p. 2805-2816 , doi : 10.1056 / NEJMoa042760 , PMID 15625332 .
  10. ↑ Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation . In: Health Technology Assessment (Winchester, England) . tape 12 , no. 16 , 2008, p. iii-iv, ix-201 , PMID 18462575 .
  11. ↑ A cost-effectiveness analysis of three treatments for age-related macular degeneration . In: Retina (Philadelphia, Pa.) . tape 30 , no. 2 , 2010, p. 212-221 , doi : 10.1097 / IAE.0b013e3181babd8e , PMID 19940805 .