Macugen: First anti-VEGF Eye Injection….so, Where's Waldo?

14 Dec Macugen: First anti-VEGF Eye Injection….so, Where's Waldo?

Like the image game “Waldo,” Macugen® seems to be lost in a sea of literature about other anti-VEGF intraocular injections.  Macugen was; however, the first intraocular injection for the treatment of wet macular degeneration.  It became FDA approved for the treatment of wet ARMD in 2004.  Where is it now?

The First anti-VEGF Intraocular Injection. Quite simply, this was a significant change for the treatment of retinal disease; specifically diabetic retinopathy and macular degeneration.  Macugen was significant for several reasons; it was the first actual drug designed to treat wet macular degeneration, it was the first ophthalmic anti-VEGF drug designed to treat a disease at the molecular level and it was the first therapeutic drug delivered by intraocular injection.

Prior to Macugen, intraocular injections were not routine, or “state of the art,” treatment for any eye disease.  The immediate success of Macugen, however, changed the way we treated retinal disease.  Direct, intraocular injections are now routine, e.g. Lucentis® and Avastin®.  Ozurdex® (Allergan), a sustained release system, and other similar systems, will also be delivered by………..intraocular injection.

What Does Anti-VEGF Mean? Vascular Endothelial Growth Factor (VEGF) was reviewed yesterday.  It is has several properties that are implicated in the disease process occurring in both diabetic retinopathy and macular degeneration.  VEGF is a protein that is produced by the retina.  VEGF must bind, or “plug in,” to a receptor for it to work.

Anti-VEGF drugs, like Macugen, Lucentis and Avastin, act to prevent VEGF from binding, or “plugging in” to its receptor.  The process is very similar to an antigen and an antibody.  Macugen is actually an “aptamer” against VEGF.  This anti-VEGF aptamer is injected directly into the eye.  It will find, and bind to, any VEGF floating around in the vitreous and retina.  The VEGF is no longer able to link to its receptor………voila, no more damage.

Different Types of VEGF are present throughout the body.  There are actually six different “isoforms” of VEGF.  Macugen was designed only against VEGF 165.  It was well known to cause vascular permeability (vascular leakage) at the time of its design.

So Where is Waldo? (i.e. What Does This Mean?)  I do not use Macugen much anymore.  There are several reasons.  The out of pocket costs to my patients are too high.  Insurance only covers so much of the drug and the rest is out of pocket expenses.  This is the same issue I have with Lucentis.  It costs my patients too much (Medicare only pays 80%).

Most importantly, the results I had with Macugen were not as impressive as Lucentis or Avastin..  One difference may be that Macugen is targeted against only one isoform of VEGF whereas the other drugs target more than VEGF 165.

“Randy”

Randall V. Wong, M.D.
Ophthalmologist, Retina Specialist
Fairfax Virginia