Age-related macular degeneration - ranibizumab
Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly. It is one of several forms of macular degeneration, all of which lead to the malfunction and death of light-sensing cells in the macula of the eye.
Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly. It is one of several forms of macular degeneration, all of which lead to the malfunction and death of light-sensing cells in the macula of the eye.
As a result, central vision gradually deteriorates, with peripheral vision remaining good. Both genetic and environmental factors such as smoking, drinking and UV light are implicated in AMD.
It exists in two forms. As many as 90% of all cases are dry or geographic atrophy AMD, with the remainder being the wet or exudative form. In the dry form, waste products from the eye accumulate under the macula, causing the macula to dry out and thin. In the wet form, retinal or choroidal neovascularisation occurs under the retina and macula. These new blood vessels can leak fluid or bleed, leading to the macula bulging and lifting up, and causing a severe distortion in central vision.
Wet type AMD is particularly difficult to treat, and it progresses rapidly. While laser coagulation can be used to destroy the newly formed blood vessels, this can irrevocably damage the retina. Photodynamic therapy with photosensitising drugs such as verteporfin has been used to inhibit growth factor mediated neovascularisation, but recurrence rates are high. Another approach would be to target the angiogenesis that is at the root of the problem, and Genentech has developed the monoclonal antibody ranibizumab to do just this.
In an open label, non-randomised escalating dose study in 27 patients with neovascular AMD, doses of 50µg to 2mg were given as an intravitreal injection.1 The maximum tolerable dose was found to be 500µg, and no serious adverse events resulted. Its safety and efficacy in escalating doses were investigated in a further study.2 Escalating doses of 300µg to 1mg or 2mg in three different schedules over 16 weeks were given to 21 patients with neovascular AMD and different lesion types. It was found to be effective in all lesion types, and 19 patients had stable or improved vision after the trial.
Sixty four patients with wet type AMD were given 300 or 500µg injections every 28 days for four to eight months or their normal treatment. Patients given the monoclonal antibody had their vision improved, while in those given normal care, it deteriorated. Phase III trials are ongoing, including a comparison with verteporfin photodynamic therapy, and it has been licensed to Novartis for development.