The research that underpins afamelanotide began over 20 years ago in the US. At that time the dramatic increase in incidence of skin cancer and its impacts were beginning to be discovered and new solutions sought. The National Cancer Institute (NCI) sponsored researchers to explore applications for various peptides as part of its melanoma prevention strategy.
This study led them to investigate peptides that acted on melanocyte receptors. The rationale behind this being that increased melanin leads to more efficient photoprotection, as melanin is a highly successful and naturally occurring UV quencher and filter. By consistently increasing melanin in the skin, skin damage from light and UV radiation can be lessened.
A synthetic analogue of the naturally occurring alpha melanocyte stimulating hormone (?-MSH) was modified to increase binding affinity to its main receptor MC1R. Altered slightly, afamelanotide lasts slightly longer in the skin and delivers a prolonged result.
Since then, the company evolved, optimized and changed the peptide synthesis of afamelanotide, it reformulated the drug in a unique fashion to deliver the drug at a desired rate. Today, Clinuvel is investigating the photoprotective properties of afamelanotide in six indications (including the rare but severe form of congenital erythropoietic protoporphyria (CEP) being investigated under compassionate use).
Above all stands our goal of becoming a truly green pharmaceutical company by continuing to build our knowledge concerning light, UV, skin and health in an age when the realities of climate change are beginning to be realised and the full benefits of medicinal photoprotection are becoming more and more apparent.
Afamelanotide (formerly CUV1647) acts by increasing the levels of melanin in the skin; and shields against UV radiation (UVR) and sunlight. Afamelanotide is delivered via a subcutaneous dissolving implant approximately the size of a grain of rice. Increased pigmentation of the skin appears after 2 days and lasts up to 2 months. It is proposed that afamelanotide will assist those patients who are most severely affected by UV and light, with the aim of improving their quality of life.
Alpha-Melanocyte Stimulating Hormone (?-MSH) is a naturally occurring peptide hormone which is released by skin cells in response to the stimulation by ultraviolet radiation (UVR). ?-MSH has a very short half life (seconds) in the blood stream, sufficient to reach and stimulate other skin cells (melanocytes) which in turn produce and release melanin, a dark brown pigment. Melanin is known for its photoprotective effect.
Afamelanotide is a chemical analogue of ?-MSH. Afamelanotide is a linear peptide with 13 amino acids. Two amino acids present in ?-MSH have been changed and amplified to produce afamelanotide. This small change creates a more stable molecule with increased potent biologic effects and a longer half life (minutes). Afamelanotide increases melanin content of the skin without exposure of the skin to the damaging effects of UVR.
Clinuvel's mission is to develop afamelanotide for the most severely affected groups of patients susceptible to phototoxicity and photosensitivity of the skin caused by UV, sun and light. Patients diagnosed with porphyria1, polymorphous light eruption, solar urticaria, skin cancers and skin lesions2, as well as patients undergoing photodynamic therapy treatment3 provoked by UV and light are clinically eligible to receive afamelanotide every two months.
Clinuvel Pharmaceuticals Ltd is an ethical pharmaceutical company focused on providing photoprotective care of the skin. Clinuvel is working closely with global regulatory agencies to develop afamelanotide as a prescriptive drug. The company intends to complete Phase III trials in late 2009. Clinuvel has been developing and testing afamelanotide since 2000. Its development is focused on the SAFE and controlled administration of the drug substance.
Implant Delivery
Clinuvel has developed a novel, controlled-release, subcutaneous implant formulation for the delivery of afamelanotide. Roughly the size of a grain of rice, the implant releases the drug over approximately 2 weeks. After 2 days, skin pigment (melanin) is increased, with the effect lasting up to two months.
Melanotans mimic the body's natural ability to produce melanin in the skin (biomimicry), but is more potent and longer acting.
Overexposure to ultraviolet (UV) and visible light radiation is responsible for skin damage. Acute exposure causes sunburn, while chronic exposure can lead to premature ageing and skin cancer.
The body responds to these damages with the release of ?-MSH, a natural occurring hormone, which stimulates the production of melanin in the skin (melanogenesis). Melanin, the pigment that provides colour to our skin, acts as a filter by reflecting, refracting and absorbing UV and visible light radiation. This pigmentary response is a natural defense mechanism that prevents further UV and visible light radiation from damaging the skin. This is the body's natural way of protecting skin from UV and visible light radiation; this phenomenon is known medically as photoprotection.
Afamelanotide, a synthetic analog of natural ?-MSH, is responsible for melanogenesis in the skin without previous UV exposure and provides medicinal photoprotection to the skin. As afamelanotide is more potent and longer lasting than ?-MSH, it can provide a physical barrier for an extended period.
Clinuvel is assessing afamelanotide's ability to provide photoprotection in patients suffering from severe UV and visible light related disorders; these are patients with the greatest clinical need for protection of the skin.
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Clinuvel is currently trialing afamelanotide in a range of light and UV related skin disorders (photodermatoses). It is proposed that afamelanotide will provide prophylactic treatment to patients suffering from these disorders by stimulating melanin to act as a photoprotective filtering the impact of UV to the skin.
Clinuvel's current clinical focus is on]
* * * Erythropoietic Protoporphyria (EPP) - absolute sun intolerance, intolerable pain suffered when exposed to light by between one in 200,000 and one in 750,000.
* * * Read more about EPP on Clinuvel Photoprotection.
* * * Find more information about EPP trials on the ANZCTR site.
* * * Polymorphous Light Eruption (PLE/PMLE) – likened to sun poisoning. Suffered by 10-20% of population.
* * * Read more about PLE on Clinuvel Photoprotection.
* * * Find more information about PLE trials on the ClinicalTrials.gov site.
* * * Phototoxicity associated with Photodynamic Therapy (PDT) for cancer – a debilitating photosensitivity to sunlight and artificial light (skin and eyes) that can last up to 90 days after PDT treatment.
* * * Read more about PDT on Clinuvel Photoprotection.
* * * Squamous Cell Carcinoma (SCC) - non-melanoma skin cancers – and Actinic Keratosis (AK), a precursor to skin cancers, in organ transplant recipients (OTRs).
* * * Read more about SCC on Clinuvel Photoprotection.
* * * Read more about AK on Clinuvel Photoprotection.
* * * More information on Clinuvel’s AK/SCC trials with organ transplant recipients is available on the ClinicalTrials.gov website.
* * * Solar Urticaria (SU) – (acute) anaphylactic reaction to sun.
* * * Read more about SU on Clinuvel Photoprotection.
* * * More information on Clinuvel's SU trial is available on the ClinicalTrials.gov website.
Clinuvel's current resources focus on the development of afamelanotide for these conditions.
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