VEGF Inhibitors

Products

VEGF inhibitors are commercially available as injectables from various suppliers. The first agent in this group to be approved was pegaptanib (Macugen) in 2004, which is now off the market in many countries.

Structure and properties

The currently available VEGF inhibitors are therapeutic proteins (biologics). They are antibodies, antibody fragments, and fusion proteins. They differ in molecular size. The Fv fragment brolucizumab has the smallest mass. Ranibizumab is derived from the same antibody used to make bevacizumab. Aflibercept is a false VEGF receptor (“decoy”) that captures growth factor (hence the -cept suffix).

Effects

VEGF inhibitors block vascular endothelial growth factor (VEGF), which is responsible for new vessel formation in wet macular degeneration. They prevent the interaction with the receptors VEGFR-1 and VEGFR-2 on the surface of the endothelial cells. This reduces endothelial cell proliferation, neovascularization (angiogenesis, new vessel formation), and vascular permeability.

Indications

For the treatment of wet (exudative) and age-related macular degeneration (AMD). In addition, other indications exist, for example, macular edema.

Dosage

According to the SmPC. The drugs are injected directly into the vitreous humor of the eye after local anesthesia. This is referred to as intravitreal application. Only a small volume is required. At the beginning of therapy, the injection is usually given monthly; later, the dosing interval is longer.

Active Ingredients

Approved biologics:

Off-label use:

Kinase inhibitors:

  • Some oral kinase inhibitors are also active as VEGF inhibitors. These are small molecules (SMMs) rather than biologics. To date, however, they have not been approved for this indication. The kinase inhibitors do not interact with VEGF, but with its receptors.

Out of commerce:

  • The oligonucleotide pegaptanib (Macugen, 2004) is no longer marketed in many countries.

Contraindications

Contraindications include:

  • Hypersensitivity
  • Infections in or around the eye
  • Inflammation in the eye (intraocular)
  • Pregnancy, lactation

Full precautions can be found in the drug label.

Interactions

There are no known interactions with other drugs.

Adverse effects

The most common possible adverse effects include reactions in the eye such as:

  • Conjunctival hemorrhage
  • Eye pain, eye irritation, foreign body sensation.
  • Cataract (cataract)
  • Vitreous detachment
  • Mouches volantes
  • Increased intraocular pressure