A patient with vitiliginous lesions on their fingers and hands
Today Clinuvel has announced that it will be commencing a new program for SCENESSE® in the common pigmentary disorder vitiligo. While this is an exciting development for Clinuvel – increasing the potential for SCENESSE® as a therapy – we feel it is vital to provide as much in-depth information on our program as is feasible to ensure our stakeholders are aware of what we anticipate will and will not be achieved with SCENESSE® as a repigmentation therapy.
Vitiligo is the most common human depigmentation disorder, affecting 0.5-2% of the population globally. The disorder affects all peoples equally, regardless of sex, ethnicity or skin type. In vitiligo, we see chronic, progressive depigmentation of the skin, generally appearing in patches or certain areas. In severe cases, these lesions can spread to result in total depigmentation. Milky-white in colour, these lesions indicate the loss of pigment melanin in that part of skin. The exact cause of the disease is unknown, though it is largely accepted to be an auto-immune disorder and there is significant evidence to this end. It is clear, however, that the disorder causes the reduced function, or even destruction, of epidermal melanocytes; the skin cells which produce melanin.
Clinically, while vitiligo does not cause physical harm, it frequently has a substantial impact upon patients’ appearance and ability to interact socially or professionally. This often translates to a significant impact on their mental health and quality of life, regardless of their initial skin type.
Vitiligo is commonly classified as segmental vitiligo (SV) and nonsegmental vitiligo (NSV). It is important to understand this distinction, as it is the latter which we intend to address with our initial trials. NSV is the most common form and comprises 72-95% of the total cases. Also known as generalised vitiligo, NSV is characterised by a bilateral distribution of depigmented areas and is often associated with a personal or family history of auto-immune disorders. We estimate that approximately 45 million individuals are affected by NSV.
The goal of treatment for vitiligo is twofold; to stop the spread of depigmentation and to repigment lesions by stimulating viable melanocytes or stem cells in the deeper layers of skin.
In order for repigmentation to occur, melanocytes must be available within the vicinity of the depigmented lesions. In some cases, the melanocytes have been completely destroyed and no viable reservoir exists, thus repigmentation is not possible without melanocyte transplantation.
Functional melanocytes can originate from three sources: unaffected melanocytes within the lesion; on the margins of the lesion and, most commonly, from stem cells residing in the hair follicles. The hair follicle unit comprises the hair follicle and its associated muscle, sweat and oil-producing glands. The melanocyte stem cells derived from this region are able to evade destruction as they do not possess the surface markers of the mature, specialised melanocytes and are thus not targeted by the immune system.
Phototherapy, or light therapy, is dosed exposure to artificial light sources to improve a disease or condition. Different wavelengths within the ultraviolet (UV) spectrum are utilised in a variety of treatment regimens, including: Broad-band UVB (BB-UVB), Narrow-band UVB (NB-UVB), UVA, PUVA and photodynamic therapy (PDT). Of these, NB-UVB is becoming the most frequently used in the treatment of dermatoses.
Phototherapy with NB-UVB has been described as a safe and effective treatment for a variety of severe skin conditions, including nonsegmental vitiligo, where the treatment can stimulate melanocytes and repigment vitiliginous lesions. NB-UVB units contain fluorescent lamps which emit UVB radiation at 311nm (+/- 2nm). NB-UVB phototherapy generally involves 5-10 minute exposures 2-3 times weekly. Treatment duration depends on the patient’s toleration of the phototherapy and the speed at which the disorder improves or resolves; phototherapy may last several months or years.
NB-UVB is currently seen as an effective treatment for stimulating repigmentation in vitiligo skin. The NB-UVB phototherapy suppresses the local immune system to stem the destruction of melanocytes and halt the progress of the disease. Further, NB-UVB therapy stimulates the proliferation of melanocytes, their migration to depigmented areas of skin and their synthesis of melanin (melanogenesis).
Melanocyte stem cells in the hair follicle unit
Upon NB-UVB irradiation, activation of stem cells begins around the hair follicles where these cells form functional melanocytes. The pigmented areas spread and coalesce as the melanocytes migrate to depigmented areas, continually producing melanin.
NB-UVB treatment may cause immediate adverse effects, including; erythema (skin redness and inflammation), pruritus (itching sensation) and xerosis (dry skin); these typically resolve with the aid of topical emollients. UVB radiation can also induce cellular and genetic damage which, long-term, can lead to photoaging and carcinogenesis (skin cancer). These potential side effects are dramatically reduced in specific narrow band therapy compared with BB-UVB (wavelength 290-320nm). NB-UVB is also the favoured phototherapy for nonsegmental vitiligo as it generally produces greater repigmentation and closer colour matching with surrounding skin.
Despite its clinical success, NB-UVB is not without its drawbacks. Phototherapy can be inconvenient for the patient, with the treatment regime requiring considerable time spent in a clinic on a regular basis. Being able to enhance or expedite this process to require fewer treatments would be of significant benefit.
USE OF SCENESSE® IN CONJUNCTION WITH NB-UVB PHOTOTHERAPY
Clinuvel’s first-in-class drug, SCENESSE®, acts by increasing the levels of melanin in the skin. Physicians working in photodermatology have repeatedly proposed the use of SCENESSE® in combination with phototherapy to reduce the risk of UV radiation exposure and potentially accelerate the melanogenic response. Thus, Clinuvel’s SCENESSE®, used alone and as an adjunct to phototherapy in nonsegmental vitiligo, aims to further stimulate melanocytes in order to repigment patient lesions in NSV. It is anticipated that SCENESSE® will aid in the recovery and migration of residual melanocytes, increasing the pigmentary response in NSV. Clinuvel now eagerly awaits clinical reports and results from the first ever trial of SCENESSE® in individuals with vitiligo.
More information
For more on our program, see today’s company announcement and our newly released webcast video
For more information on vitiligo, see the Clinuvel skin & health vitiligo page
Image reference
Vitiligo2.jpg from Jmh649, posted to Wikimedia commons
