Medicinal photoprotection trial to assess safety and efficacy in organ transplant recipients
Clinical and regulatory progress:
- Commenced Phase II trial (CUV011) in 2007 in Australia and Europe
- Interim safety analysis results announced in December 2011 - Read the announcement
Skin cancer and Organ Transplant Recipients (OTRs)
Cumulative exposure of skin to ultraviolet radiation (UVR; light in the range of 290-400nm) results in damaged skin cells and DNA; the primary causes of common skin cancers. The lack of a functioning immune system means the body is less able to defend against these damaged cells replicating unchecked, ie, skin cancer.
Due to the essential life long use of immunosuppressant drugs to prevent organ rejection by their own bodies, OTR patients are at an extreme risk of skin cancer compared to the general population. It has been found that OTR patients are up to 65 times more likely to develop skin cancer than those who have not had an organ transplant.
It is estimated that there are over 500,000 organ transplant recipients living worldwide, with numbers increasing as advances in medical and pharmaceutical technology improve transplant success rates and patient survival times.
About Actinic Keratosis (AK)
An actinic keratosis is a precancerous skin growth that is discrete, dry, rough adherent of scaly lesions, usually caused by sun exposure. Also known as AK (or solar keratosis, SK), actinic keratosis is a term derived from actinism, meaning the property of radiant energy, especially in the visible and ultraviolet spectral regions by which chemical changes are produced, and keratosis, meaning excessive growth of horny tissue of the skin.
Approximately 50% of the world's population has problems with AK. In the US, consultations for AKs are the second most common reason for patient visits to dermatologists, and treatment of these lesions has become a major part of dermatology practice. The prevalence of AKs varies geographically with the incidence amongst Australians 40 years of age or older reported to be 40-60% compared with approximately 10-20% of the population in Europe and the US.
The major clinical consequences of AK's are that these lesions may transition into skin cancer.
About Squamous Cell Carcinoma (SCC)
Also known as SCC, squamous cell carcinoma is a malignant tumour of the skin and the second most common form of skin cancer. SCC is caused by prolonged exposure to UVR. There has been a global increase in the incidence of SCC recorded in fair skinned people; their lack of skin pigmentation is thought to be a determining factor in developing SCC or skin tumours.
The link between Actinic Keratosis and Squamous Cell Carcinoma
Recently AKs have been demonstrated to be an initial step in a continuum with squamous cell carcinomas (SCC) at the opposite end. Currently there is no available technology that allows distinction between lesions that will regress, remain stable or progress to invasive skin cancers, so the majority of AKs are treated because of the concern that they may progress to invasive SCC, a malignant form of skin cancer.
Clinical testing of SCENESSE® (afamelanotide 16mg) in OTR patients
SCENESSE's ability to activate melanin production may be utilised to provide medicinal photoprotection to assist in alleviating UV-related skin disorders which are exacerbated by UVR.
There is a direct correlation between the incidence of skin cancer and the natural pigmentation of an individual's skin. Afro Americans who have undergone organ transplants have a lower incidence of skin cancer than Caucasian organ transplant patients. In the US, for instance, incidence rates of melanoma (pigmented malignancies of the skin) in white males amount to 25:100,000 compared to black males who have an incidence of 1.4:100,000. In comparison, for white females vs. black females the incidence rate is 17.9:100,000 vs. 1.1:100,000 (Tsai, et al. 2005). Such findings add to the validation of our approach with afamelanotide.
It is not expected that SCENESSE® (afamelanotide 16mg) will totally eliminate the effects of previous long term exposure to UVR but that it will eliminate, reduce or mitigate the effects of future continued exposure.
- Anwar J, Wrone DA, Kimyai-Asadi A, Alam M. 'The Development of Actinic Keratosis into Invasive Squamous Cell Carcinoma: Evidence and Evolving Classification Schemes', Clinics in Dermatology 2004;22:189-96.
- Dwyer et al. ‘Cutaneous Melanin Density of Caucasians measured by spectrophotometry and risk of malignant melanoma, basal cell carcinoma and squamous cell carcinoma of the skin’. Am J Epidemiol. 2002 155:614-21.
- Euvrard S, Kanitakis J, Decullier E et al. 'Subsequent Skin Cancers in Kidney and Heart Transplant Recipients after the First Squamous Cell Carcinoma', Transplantation 2006;81(8):1093-1100.
- Hadley, et al. ‘The Proopiomelanocortin system’. An. N.Y. Acad. Sci. 1999, 885:1-21.
- Higashi MK, Veenstra DL, Langley PC. 'Health Economic Evaluation of Non-Melanoma Skin Cancer and Actinic Keratosis'. Pharmacoeconomics 2004;22(2):83-94.
- Hoffman et al. ‘Malignant melanoma in Cape Town, South Africa’. Br J Dermatol. 1998, 138:998-1002.
- Kromberg et al. ‘Albinism and skin cancer in Southern Africa’. Clin. Genet. 1989, 36:43-52.
- Oppel T, Korting HC. 'Actinic Keratosis: The Key Event in the Evolution from Photoaged Skin to Squamous Cell Carcinoma', Skin Pharmacology and Physiology 2004;17(2):67-76.
- Spencer JM, Hazan C, Hsiung SH, Robins P. 'Therapeutic decision making in the therapy of actinic keratoses'. Journal of Drugs in Dermatology 2005;4(3):296-30.
- Tsai, et al. ‘Cutaneous, ocular and visceral melanoma in African Americans and Caucasians’. Melanoma Res. 2005, 15:213-217.