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The curative combination of light and sensitizing agents has been known since antiquity; the ancient Egyptians used an extract of the plant sorrel in conjunction with sunlight to bring relief to sufferers of skin complaints. However, it was not rediscovered until the late 19th century when the Danish physician Finsen found he could treat Lupus vulgaris using ultra-violet light from a mercury arc-lamp. Princess Alexandra, the future queen of King Edward VII and a great patroness of the medical sciences, brought Finsen and his discovery of phototherapy to the Royal London Hospital. A statue of the Princess in the gardens of the hospital still stands commemorating this event. In 1913, Meyer-Betz demonstrated the phototoxicity of certain sensitisers by injecting himself with 200 milligrams of 'hematoporphyrin derivative' or HpD. By 1924, Policard had discovered that some malignant tumors accumulated certain sensitisers. It was not till 1975, however, that the fortuitous combination of light and sensitisers in what has become know as photodynamic therapy or PDT, was found to be able to detect and treat cancers.

By 1976, the first successful trials with human volunteers using HpD had been initiated. In January 1998, a partially purified version of HpD called Photofrin (porfimer sodium, marketed by Quadralogics Technologies, QLT, based in Vancouver, Canada) became the first photosensitiser approved for use in cancer therapy. Though in many ways a successful PDT drug, after 30 years of development, porfimer sodium suffers from a number of shortcomings. These include it being a difficult to reproduce mixture of compounds (some of which are PDT inactive), lack of targeting to specifically pathological tissues and slow clearance from the system (leading to patients being acutely photosensitive for sometime after treatment), and poor drug/light interaction. HpD absorbs strongly in the blue region of the electromagnetic spectrum, and blue light has little skin penetration, limiting HpD’s use to conditions on or near external and internal bodily surfaces easily accessed by a light source.

Since then, new so-called ‘second generation’ PDT sensitisers have been developed with much improved drug/light interactions. The most successful of these has been Verteporfin, developed by QLT and marketed by Novartis for the treatment of AMD. The market success of this drug can be gauged from its annual sales of around half a billion dollars a year. Verteporfin works by targeting leaking proliferating blood vessels in the cornea that give rise to the AMD condition. After injection, the drug is allowed to equilibrate in the eye, and then the cornea is irradiated through the iris with a cold red laser.

Another successful PDT drug especially in head and neck cancers is Foscan (Temoporfin). Originally developed by Scotia Pharmaceuticals, Foscan has an excellent drug/light interaction, but suffered from a series of poorly organised clinical trials that led to its non-acceptance by the FDA and initially by the EMEA. This in turn led to Scotia’s demise and an unfortunate market slur on the good name of PDT. However, Foscan was acquired by Biolitec and is now being marketed in Europe for indications including head and neck cancers. Biolitec reported Foscan revenues up 82% in the nine months to end May 2006, and Foscan is reimbursed in most European territories, the most recent being Belgium in Jan05, at €7,000 per treatment unit.

Other ‘second generation PDT sensitisers are coming to market or are in various stages of Phase II and Phase III trials for a variety of conditions. None of these new sensitisers, however, are targeted, so all suffer to a greater or lesser extent from the post-treatment problem of photosensitivity. PhotoBiotics’ targeted approach will counter this, ensuring sensitisers are directed specifically to pathological tissues.

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