Susan Aldridge
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News of a 'bionic eye' — a device that gives blind people some level of vision — has focused attention on ophthalmic medicine.
Most patients with a visual problem won't be getting new eyes, but they do represent the growing market for smarter formulations
of existing drugs, such as preservative-free drugs, or reprofiling certain molecules specifically for the eye.
There is a growing number of specialist pharmaceutical companies searching for opportunities to develop and manufacture new
ophthalmic medicines. One of these is Ophthaltec Ltd (UK), which is working towards commercializing research at the UK's University
College London (UCL) Institute of Ophthalmology on a project regarding the detection of apoptosing retinal cells, which allows
for much earlier detection of glaucoma. The company is also interested in cell therapy for the eye and in reprofiling drugs;
these could be compounds that have failed at a late stage of development for their primary indication or that are already
successful and have a mode of action that could also be applicable to an eye disease.
The author says...
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"The challenges in the ophthalmic area largely centre on finding effective therapies for the main ophthalmic diseases that
affect people in the Western world — age-related macular degeneration (AMD), glaucoma and diabetic retinopathy," says Peter
Adamson, CEO of Opthaltec. "The difficulty in finding effective treatments is that we have such a poor understanding of the
disease biology and pathology, particularly in mechanistic terms."
FormulationAdamson explains that when reprofiling an existing drug, or developing a new one, a key issue is formulation; whether an eye-drop
or cream is needed or whether the drug can be injected into the eye. The advantage of the topical approach is that systemic
exposure is limited and, usually, less of the drug is needed than in an oral dose. However, as the surface of the eye is vascularized,
the level of systemic exposure is not zero; for example, eye-drops for glaucoma treatment cannot be used in patients with
impaired lung function because systemic exposure can cause bronchospasm. In general, the lower level of systemic exposure
reduces the exposure of other organs to the drug substance, limiting side-effects and potential organ toxicity, according
to Adamson. "The eye can be regarded as a closed biological location," he says.
Injecting a drug into the eye may sound risky to most people but is, in fact, routine and the preferred route for antiangiogenic
drugs, such as Macugen (pegaptanib) and Lucentis (ranibizumab), which are monoclonal antibodies used for AMD. Also in this
category is Avastin (bevacizumab), which is an example of a drug developed for another purpose that has been adopted for ophthalmic
use. It is already licensed for colorectal cancer, breast cancer and nonsmall cell lung cancer, but is in clinical trials
for AMD, as well as already being prescribed off-licence for the condition.
The disadvantage of eye drops and creams is that the drug usually has to penetrate the cornea and there is also the problem
of low residency time as the drug tends to get washed away by tears. Therefore, the concentration of the drug must be high,
and the API must be highly soluble in a non-irritable solvent and must be balanced in terms of salt concentration and pH.
To address these issues, some ophthalmology companies have formed partnerships with hospitals. One example is Opthaltec, which
has partnerships with UCL, Moorfields Eye Hospital and Moorfields Pharmaceuticals (UK). The hospital was involved in the bionic
eye trials and is also renowned for its work on cell therapy. More information on Moorfields can be found in the July 2007
issue of Pharmaceutical Technologist.1
