Macular degeneration - pegaptanib
The most common causes of irreversible blindness in the elderly are exudative age-related macular degeneration and diabetic macular oedema.
The most common causes of irreversible blindness in the elderly are exudative age-related macular degeneration and diabetic macular oedema.
There is no effective cure for either, with treatment options being thermal laser treatment or photocoagulation therapy, neither of which is effective in most cases.
It is believed that vascular endothelial growth factor (VEGF), a cytokine that plays an important part in angiogenesis and is required for normal vascular development, could be involved in the development of these eye disorders in the elderly. Patients with the conditions have high concentrations of VEGF within their eyes, so if the cytokine were to be suppressed, it may have the effect of improving their eyesight.
Gilead Sciences has developed an aptamer against VEGF that may have the desired effect. It has now been licensed to Eye Tech Pharmaceuticals. An aptamer is an oligonucleotide that has been isolated in order to bind to specific molecular targets. Gilead's pegaptanib sodium is the sodium salt of a 40,000 molecular weight polyethylene glycol conjugated 28 unit oligonucleotide which binds selectively to the major soluble human VEGF isoform, VEGF165, with high affinity.1 Preclinical studies showed it to be a potent inhibitor of VEGF-induced vascular permeability, blood vessel growth and neovascularisation.
A multicentre, open label, dose escalating Phase Ia study has been carried out in 15 patients over the age of 65 with age-related macular degeneration. They were given a single intravitreal injection of the aptamer, of 0.25, 0.5, 1 or 3mg per eye.2 The dose limiting toxicity was not reached, because of problems with the formulation of higher doses. Some mild to moderate adverse events were seen, and three months after treatment, 80% had stable or improved vision, and the vision of 27% of the patients had improved significantly.
A further study in 36 patients receiving intravitreal injections of pegaptanib showed similar improvements, with 80% again being stable or improving, and 30% whose eyesight improved significantly, again with no serious side effects.3 Phase II/III multicentre randomised double blind controlled comparative trials are now being carried out to investigate the efficacy of pegaptanib in the treatment of age-related macular degeneration and diabetic macular oedema.