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Pharmaceutical Technology Europe
... profit margins in ophthalmology are very attractive and the market is increasing as the incidence of eye disease grows with the ageing population.
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 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."
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Adamson 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
London appears to be a global centre for ophthalmic pharmaceutical companies, but there is significant work going on elsewhere in the world. OphthalmoPharma (OPPH; Switzerland) also focuses on the development of drugs and medical devices for ophthalmology. Richard White, Director of Pharmacology and Toxicology, believes that ophthalmology has been neglected by large pharma as the market size for most of the indications is currently lower than the 'blockbuster' (>$1 billion) potential for drugs in oncology, central nervous system or cardiology. Despite this, profit margins in ophthalmology are very attractive and the market is increasing as the incidence of eye disease grows with the ageing population. Further potential for market growth comes from the significant number of untreated patients and the severity of the diseases, many of which ultimately lead to loss of sight.
OPPH sources, selects and in-licences compounds and technologies close to commercial development. Products are moved across the development phases that add the most value and licensed out to large pharmaceutical companies and ophthalmic specialty firms. OPPH's lead programme is a novel formulation and delivery platform, based on third generation monosubstituted cyclodextrins, for the ocular administration of new molecules and for new applications of established drugs for the treatment of glaucoma, dry eye syndrome, age-related macular degeneration and inflammation.
Finally, there is news that one of the world's leading eye health companies, Bausch & Lomb (NY, USA) is teaming up with the drug discovery company, Galapagos (Belgium). The research agreement gives the larger company access to a group of small molecules thought to have huge potential in ophthalmic applications. "The molecules come from a programme of ours on a target that could be important in eye disease, which were very effective when tested in animals," explains Galapagos CEO, Onno van de Stolpe. "We want to stay focused as a company on bone and joint disease, but are pleased that these molecules may have another clinical application."
If Bausch & Lomb find a compound of interest from this partnership, Galapagos will develop it further prior to clinical trials. Such collaborations are likely to become increasingly common as the ophthalmic pharmaceutical market grows.
1. A. Krol, Pharmaceutical Technologist, 2(4), 20–22 (2007). www.nxtbook.com/nxtbooks/advanstaruk/pt0707