A new article was published last week looking at a small pilot study of SCENESSE® (afamelanotide) in acne vulgaris. Before discussing this piece specifically, I think it is relevant to briefly review melanocortins and their receptors.
The active ingredient in SCENESSE®, afamelanotide, has been the focus of over 80 peer reviewed journals (as well as being mentioned in at least 100 more) since the initial formulatory work with the drug began in the 1980s. In the last two years alone the drug and its actual or theoretical application in the clinic have been presented at least 20 times at various global scientific forums. This growing library of resources reflects the enthusiasm of the medical community to put a new compound through its paces, both in vitro and in vivo.
While much of this activity has focused on trial results or observations – such as those presented at the American Academy of Dermatology meeting earlier this year – others have chosen to focus on the potential of the drug to address various disorders or diseases, chiefly in dermatology, but also in other medical fields.
Afamelanotide is from a family of molecules known as melanocortins, based on the naturally occurring hormone alpha-Melanocyte Stimulating Hormone, or alpha-MSH. Afamelanotide binds with a particular receptor – melanocortin 1 or MC1R – on the walls of melanocytes – pigment producing skin cells – which in turn stimulates melanin in the skin.
Research into the properties of natural alpha-MSH has shown it to have a range of functions beyond pigmentation, with the natural hormone binding to further melanocortin receptors (numbered 1-5) present on various cells across the human body. Taking a step further, the activation (with an agonist such as alpha-MSH) or blocking (with an antagonist) of melanocortin receptors across the body could unlock a vast array of therapeutic potential.
Closer to our work, melanin also plays a number of roles in human skin. At Clinuvel we focus on two of its primary and best understood functions: photoprotection and pigmentation.
With a basic understanding of the role that melanocortins and alpha-MSH play in the functioning of human skin, it’s easy to see why there has been so much academic focus on melanocortins – these receptors and their agonists and antagonists present a range of possibilities for modern medicine, much of which we’re yet to fully understand.
This brings us back to the undertaken pilot acne study.
Acne vulgaris (just acne to most of us) is one of the most common dermatological disorders, affecting nearly the entire population at some stage of their life, but most commonly during adolescence. Acne is largely caused by a blocking of pores in the skin, the accumulation of sebum and subsequent inflammation resulting in comedones, pimples. For most people, acne is a moderate nuisance, destined to ruin high school photos and first dates. For up to 14% of people, however, acne becomes a distressing battle with the skin which continues well into adulthood. For these patients, a range of over the counter and prescription medications exist, with oral steroids currently used as the golden standard to reduce severe acne.
According to a range of non-clinical studies, natural alpha-MSH is widely understood to have an anti-inflammatory and anti-oxidative effect when it binds with certain melanocortin receptors, including MC1R in skin. Thus, the scientific question was posed: would afamelanotide, an alpha-MSH analogue, exhibit the same properties as the natural hormone when given to patients with acne?
After administering the drug to three adult male patients and observing the progress of their acne over eight weeks the jury is still out, but the authors of the piece – a team from the University of Muenster in Germany – conclude that the drug warrants further investigation for this common disease.
For the moment, though, it makes little sense for Clinuvel to pursue an acne program. The reasons are numerous, but many are covered in my piece last week on effective drug development. The opportunity may arise to return to a larger study for acne with a melanocortin drug and, if so, it is certain that this early stage clinical work will have played a pivotal role in advancing dermatological therapies.
- Lachlan
Reference
Bohm M, Ehrchen J, Luger TA, (2012). “Beneficial effects of the melanocortin analogue Nle4-d-Phe7-α-MSH in acne vulgaris.” JEADV. ePub 27 July 2012.
Image reference
A cross section of skin with acne from http://www.clinuvel.com/en/skin-science/skin-conditions/common-skin-conditions/acne-vulgaris
