Afamelanotide - Historical Development

Historical Development

-α-MSH was first synthesized at the University of Arizona. Researchers there knew that one of the best defenses against skin cancer was melanin activated in the skin, a tan. They hypothesized that an effective way to reduce skin cancer rates in people would be to induce the body's natural pigmentary system to produce a protective tan prior to UV exposure. The body's naturally occurring hormone α-MSH causes melanogenesis, a process by which the skin's pigment cells (melanocytes) produce the skin's pigment (melanin). They tested to see if administering this endogenous hormone to the body directly could be an effective means of sunless tanning. What they found was that while it appeared to work, natural α-MSH had too short a half life in the body to be practical as a therapeutic drug. The team then searched for a more potent and stable alternative.

After synthesizing and screening hundreds of molecules, the researchers, headed by Victor J. Hruby and Mac E. Hadley, found a peptide, -α-MSH, that was approximately 1,000 times more potent than natural α-MSH. They dubbed this new peptide molecule "Melanotan" (later Melanotan-1, now known as afamelanotide). They subsequently developed another analog, Ac-Nle-cyclo-NH₂), which they called "Melanotan II". The scientists hoped to use these peptides to prevent melanoma by stimulating the body's natural pigmentary mechanism to create a tan without exposure to harmful levels of UV radiation. This in turn, they hypothesized, could reduce the potential for skin damage in the tanning population that could lead to skin cancer.

The scientists licensed their patented peptides, via a technology transfer company, to a number of biotechnology companies intent on developing them into drugs. Afamelanotide (formerly the proprietary CUV1647) is currently being tested, in an implant delivery formulation, and clinically trialed by the Australian company Clinuvel Pharmaceuticals, for a series of conditions affecting the skin including erythropoietic protoporphyria (EPP), polymorphous light eruption (PMLE), solar urticaria (SU), phototoxicity associated with systemic photodynamic therapy and actinic keratosis (AK) and squamous cell carcinoma skin cancer in patients who have received organ transplants.