Afamelanotide, a first-in-class investigational chemical analogue of alpha-melanocyte-stimulating hormone, is a melanocortin-1 agonist that activates melanocytes and increases melanin levels in the skin.

Treatment with the controlled-release afamelanotide implants was life changing for study participants, Dr. Elisabeth I. Minder noted.

"You have to understand that EPP [erythropoietic protoporphyria] patients are conditioned early in life that sunlight is harmful]
EPP is a rare inherited disease characterized by severely painful, often intolerable phototoxic attacks lasting for days. An estimated 10,000 individuals are affected worldwide she said.

The afamelanotide implant (Scenesse) is also in clinical trials for more common diseases, including vitiligo, solar urticaria, and polymorphous light eruption, as well as for prevention of actinic keratoses and squamous cell carcinomas in organ transplant recipients.

The European phase III EPP trial involved 100 affected patients who were randomized double blind to a year's worth of alternating treatment cycles consisting of a subcutaneous implant of 16mg of Melanotan I (afamelanotide) lasting for 60 days followed by 60 days of a placebo implant.

A total of 91 patients completed the study. The low dropout rate was testimony to how grateful participants were to finally have access to an effective therapy for their disorder, even if for only half of the study period, Dr. Minder said.

Daily pain diaries demonstrated that patients experienced significantly fewer days of severe, moderate, and mild pain during the periods in which they were being treated with afamelanotide.

During the active-treatment periods, patients reported spending significantly more time outdoors exposed to the sun. More than half of patients reported spending greater than 6 hours per day outdoors while they were on afamelanotide, something that was unthinkable at baseline.

Only two adverse events were more frequent during active treatment]
Session chair Dr. Maurice Van Steensel of Maastricht (Netherlands) University commented that a truly double-blind study is impossible with afamelanotide because the alpha-melanocyte-stimulating hormone analogue causes tanning. For this very reason, he added, the tanning industry may be interested in this agent as a sunless tanning product.

In an earlier open-label pilot study, Dr. Minder and her associates showed that treatment with afamelanotide increased tolerance to exposure to artificial light under controlled conditions by 11-fold (N. Engl. J. Med. 2009).

Further Research Is Warranted
Having cared for patients with erythropoietic protoporphyria, as well as other forms of photo-sensitivity, I understand the need for effective therapies in this area. The results of the treatment in the study are impressive.

As pointed out by others, it is very difficult to run a completely blinded study with the drug since it does induce a visible tan so that both patients/researchers are aware of the treatment.

In addition, the end points studied are very subjective reports of pain. More importantly, we should be concerned about the possibility of adverse effects of a melanocortin peptide hormone which stimulates melanocytes.