Therapy Analysis - AMD
Current options for treatment
Research has considerably improved our knowledge of the pathophysiology of AMD, identifying numerous common risk factors and familial components. Despite this increased understanding, the exact cause remains unclear. Certain genes have been implicated in the pathophysiology, including complement system factor H and B, which play a role in immune response; in one study, specific variants of one or both were identified in 76% of patients. Research also points to the build up of free oxygen radicals as a potential disease trigger. As mentioned previously, it is not known whether the presence of an increased number of drusen also raises the risk of AMD, or is symptomatic of the underlying cause of AMD. There are also a number of risk factors associated with the development of AMD, with age obviously being the most significant. In the US, people aged 50 have a 2% chance of developing AMD, whereas at age 66 to 74 years, this risk increases to 10%. The prevalence increases to 30% in patients 75 to 85 years of age and continues to rise over time. Links between smoking, elevated levels of cholesterol and hypertension have also been established, along with a familial risk factor, where AMD has been shown to be hereditary in some families.
There is currently no cure for AMD and no available treatment for dry AMD. However, in research carried out by the National Eye Institute, its AREDS study did show that a specific high dose formulation of antioxidants and zinc could significantly delay the onset of advanced dry AMD. Adopting this strategy, Pipex Pharmaceuticals, in collaboration with the University of Michigan, is developing orally active zinc-monocysteine complexes. In a Phase II trial in 80 dry AMD patients, the compounds resulted in improvement in visual activity, contrast sensitivity and photorecovery times compared to placebo, highlighting a promising therapeutic avenue for development. Also in Phase II trials for dry AMD are Neurotech's NT-501, an intravitreal implant releasing ciliary neurotrophic factor which protects against photoreceptor degeneration, and Sirion Therapeutics' formulation of fenretinide, which reduces the accumulation of lipofuscin in the eye by inhibiting the formation of serum retinol. Pharmaprojects lists 76 compounds in active development for AMD (Graph 1); wet AMD being the primary pharmaceutical focus with 18 compounds in active development and 4 launched compounds, including some innovative biotechnology compounds. These treatments focus on preventing disease progression and usually target the formation of CNV
The first compound launched for AMD was Visudyne (verteporfin) in 1999, a light activated benzoporphyrin derivative, developed by QLT and licensed to Novartis Ophthalmics for use in photodynamic therapy (PDT). Administered intravenously, it localizes in the cells of the new abnormal blood vessels, formed as a result of CNV. The eye is then subjected to non-thermal laser irradiation, producing reactive oxygen radicals, which damage the endothelium and cause occlusion of the harmful new vessels. PDT remains the standard treatment available on the NHS in the UK and provides a significant advantage over previous methods of treatment such as hot laser surgery, which causes damage to the surrounding tissue. However, use of PDT is restricted to 'predominantly classic CNV', which represents only 40% of eyes with wet AMD, leaving the majority of patients ineligible for treatment.
