QLT PhotoTherapeutics has carried out extensive work on the second-generation photosensitizer verteporfin (benzoporphyrin- derivative monoacid ring A) (see http://www.qlt-pdt.com, [81]). In collaboration with CIBA Vision Corporation (Duluth, GA, USA), verteporfin (Visudyne™) is presently undergoing Phase III clinical trials for the treatment of wet age-related macular degeneration (AMD). Furthermore, an NDA has been submitted to the FDA for the use of Visudyne in AMD, as well as a marketing clearance application for the European Union through the European Medicines Evaluation Agency (EMEA).

AMD is the leading cause of blindness in humans over the age of 50 and involves the rapid growth of abnormal blood vessels under the central retina. Leaking from these abnormal vessels causes scarring and an accelerated loss of visual acuity and there is no adequate treatment protocol for 80–90% of these patients[82]. As PDT is known to induce vascular shutdown, compounds such as verteporfin are ideal for treating this condition. Initial results have been very promising, showing a significant preservation of vision in a number of patients.

Verteporfin is also in Phase III clinical trials for cutaneous non-melanoma skin cancer and Phase I/II trials against other non-melanoma skin cancers (such as multiple non-melanoma skin cancer), psoriasis[83], and psoriatic and rheumatoid arthritis. Extensive preclinical work has been carried out using verteporfin as a therapy for multiple sclerosis and Barrett’s oesophagus and as an agent to achieve endometrial ablation and bone marrow purging[84].

Verteporfin has a much stronger absorbance at a longer wavelength (690 nm), where tissue penetration of light is 50% greater than that of Photofrin at 630 nm. In addition, verteporfin is rapidly absorbed by the tumour, reaching an optimal tumour–normal tissue ratio 30–150 minutes after intravenous injection, and is rapidly cleared from the body so that skin photosensitivity only lasts a few days.