Anecortave acetate in the treatment of age-related macular degeneration

Abstract

RETAANE 15mg (anecortave acetate suspension) is under investigation to treat exudative age-related macular degeneration (AMD), the single largest cause of blindness in the Western world, affecting over 15 million people in the USA. RETAANE suspension is a unique synthetic cortisene and has antiangiogenic properties that were established in multiple experimental models of angiogenesis. The molecule acts at multiple sites of the angiogenic cascade. Clinical trials in patients with exudative AMD have demonstrated the excellent safety record of both the drug anecortave acetate and the posterior juxtascleral depot (PJD) administration procedure. A pivotal study comparing RETAANE suspension with placebo showed a significantly higher chance of maintaining vision in the treatment (73%) as compared with placebo (47%). Another study compared RETAANE suspension with Visudyne photodynamic therapy, revealing no statistically significant differences between the two treatments over 24 months. AMD is a multi-faceted disease and therefore a molecule such as RETAANE suspension with a unique mechanism of action, demonstrated clinical efficacy, and retreatment every six months is an important potential treatment option which should be further investigated both as a monotherapy or in combination with other treatment strategies.

Figure 1

Schematic diagram of the anecortave acetate, a unique synthetic cortisene. Modifications made to the cortisol parent molecule are shown.

Figure 2

The unique design of the blunt tinted posterior juxtascleral depot cannula ensures that anecortave acetate is delivered directly behind the macula while leaving the globe intact.

Figure 3

The counter pressure device prevents reflux of anecortave acetate when placed as posterior as possible in position with the posterior juxtascleral depot cannula.

Figure 4

Evidence supports use of counter pressure device (CPD) for managing reflux. Plasma concentrations of anecortave desacetate in patients with the CPD (C-04-50) were the same as the plasma concentrations in patients without the CPD and had no reflux (C-02-47). Patients (C-02-47) with reflux had 4 fold lower levels of anecortave desacetate than patients without reflux. In the C-04-50 study, the CPD prevented reflux in 100% of the patients.

Figure 5

Anecortave acetate blocks proteolytic cascade in the vascular endothelial cells (VEC).